The DOI matches its Crossref record; 212 of the 214 references it cites were found in a registry or an index; none of the 126 sources its claims cite is checked for support yet.
Microbiome–microglia connections via the gut–brain axis
Open accessAbstract
Microglia, the resident immune cells in the brain, are essential for modulating neurogenesis, influencing synaptic remodeling, and regulating neuroinflammation by surveying the brain microenvironment. Microglial dysfunction has been implicated in the onset and progression of several neurodevelopmental and neurodegenerative diseases; however, the multitude of factors and signals influencing microglial activity have not been fully elucidated. Microglia not only respond to local signals within the brain but also receive input from the periphery, including the gastrointestinal (GI) tract. Recent preclinical findings suggest that the gut microbiome plays a pivotal role in regulating microglial maturation and function, and altered microbial community composition has been reported in neurological disorders with known microglial involvement in humans. Collectively, these findings suggest that bidirectional crosstalk between the gut and the brain may influence disease pathogenesis. Herein, we discuss recent studies showing a role for the gut microbiome in modulating microglial development and function in homeostatic and disease conditions and highlight possible future research to develop novel microbial treatments for disorders of the brain.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review synthesizes evidence that the gut microbiota influences microglial maturation, identity, and function through gut–brain axis pathways including the vagus nerve, systemic circulation, and microbial metabolites. It argues that dysbiosis may contribute to microglial dysfunction in neurodevelopmental and neurodegenerative disorders such as autism spectrum disorder (ASD) and Parkinson’s disease (PD).
Key findings
- Microglia make up ∼5–15% of total brain cells and mature stepwise from early to pre- to adult microglia. Germ-free (GF) mice show immature microglial gene expression and morphology, with impaired responses to LPS and lymphocytic choriomeningitis virus; a diverse microbiota—not just bacterial exposure—is required, and antibiotic depletion in adulthood reverts microglia toward an immature phenotype.
- Gut–brain communication routes include the vagus nerve, intestinal barrier/peripheral immune signaling, and bacterial metabolites. Short-chain fatty acids (SCFAs; acetic, propionic, and butyric acid make up ∼95% of gut SCFAs) rescue the immature microglial phenotype in GF mice, while FFAR2-deficient SPF mice resemble GF mice. Other microbial neuroactive substances include serotonin (90% produced in the gut), tryptophan metabolites, GABA, and acetylcholine.
- Disease associations include ASD, where GI symptoms occur in 23–70% of patients and fecal samples show increased Clostridium and Lactobacillus with decreased Bacteroidetes and Bifidobacterium; maternal immune activation models show microglial maturation disruption, and Bacteroides fragilis administration rescues behavioral and GI defects. In PD, >80% of patients report GI dysfunction 10–20 yr before motor symptoms, SIBO occurs in 25–54.5%, and GF α-synuclein-overexpressing mice show reduced motor deficits, GI dysfunction, and microglial activation; SCFA feeding restores deficits. Table 1 also lists schizophrenia, major depressive disorder, Alzheimer’s disease, amyotrophic lateral sclerosis, and multiple sclerosis as neuropathologies with both microglial dysfunction and microbial dysbiosis.
Methods
- Narrative review; no primary data are reported. It synthesizes published human and animal studies on the gut microbiome, microglia, and gut–brain axis.
- Evidence discussed includes GF and specific pathogen–free mice, antibiotic depletion, fecal microbiota transplant, probiotics/prebiotics, SCFA supplementation, vagotomy and vagus nerve stimulation, human postmortem brain tissue, PET imaging, and fecal microbiota analyses.
- Main analysis is qualitative integration of mechanisms and disease associations; no systematic search strategy or meta-analysis is described.
Limitations
- Stated in the paper: ASD pilot studies have small sample sizes; the maternal immune activation model has limitations in replicating complex ASD symptomatology; exact SCFA signaling pathways and how GI signals propagate to the CNS are poorly understood; whether disease-associated microbial alterations are a cause or consequence of altered brain function is unclear; the role of SCFAs in PD models is uncertain due to concentration- and region-dependent effects; interindividual variation in PD microbiota is high.
- Evident from the text: as a narrative review, it does not systematically assess study quality or quantify effects; many conclusions rely on animal models and correlative human data, so causality in humans remains unestablished.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
88 Not checked yet · 41 Own interpretation · 1 Own method
None of the sources cited for this claim have been checked yet.
In the paper
“microglial activity is now known to be influenced by factors originating outside the CNS, including the gut.”
§ Microbiome–microglia connections via the gut–brain axis > Introduction
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This review highlights evidence demonstrating the various mechanisms by which the gut microbiota can influence microglia in both homeostatic and disease conditions.”
§ Microbiome–microglia connections via the gut–brain axis > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Microglia from adult GF mice also display differential expression of genes associated with microglial maturation, including down-regulation of genes that regulate cell activation and immune system defense pathways, such as Mapk8, IL-1α, Ly86, Jak3, and Stat1, all of which are normally highly expressed in adult microglia (Fig. 1; Erny et al., 2015; Matcovitch-Natan et al., 2016).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain axis influences microglia development and function > Diverse gut microbiota is a prerequisite for adult microglial maturation and function
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Sophisticated crosstalk between the CNS and the gut microbiome (known as the gut–brain axis) is critical for several facets of CNS physiology, including microglial development and function (Mayer et al., 2015; Fung et al., 2017).”
§ Microbiome–microglia connections via the gut–brain axis > Introduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, the gene expression profile and behavior of microglia from GF mice or under microbiota-depleted conditions is reminiscent of an immature microglial phenotype, indicating that input from gut microbiota is required for microglia to progress to later stages of cellular maturation and adequately fulfill their role in immune surveillance.”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain axis influences microglia development and function > Diverse gut microbiota is a prerequisite for adult microglial maturation and function
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In SPF mice, a diverse gut microbiota promotes microglial development and maturation.”
§ Microbiome–microglia connections via the gut–brain axis > Microglia during development and adulthood > Microglia maturation
What the sources say
- Not checked yetcites Erny et al., 2015 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gut microbiota influences microglial development and maturation.”
§ Microbiome–microglia connections via the gut–brain axis > Microglia during development and adulthood > Microglia maturation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the presence of a complex and diverse microbial community, rather than exposure to gut bacteria per se, appears to be a prerequisite for proper microglial development and function.”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain axis influences microglia development and function > Diverse gut microbiota is a prerequisite for adult microglial maturation and function
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“recent genetic studies provide evidence that microglia contribute to the pathogenesis of several neurodegenerative and neurodevelopmental disorders (Salter and Stevens, 2017).”
§ Microbiome–microglia connections via the gut–brain axis > Introduction
What the sources say
- Not checked yetcites Salter and Stevens, 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Consistent with patterns observed prenatally, microglia from adult GF mice, lacking constant postnatal input from gut microbiota, show distinct differences in density and morphology compared with those derived from SPF mice (Erny et al., 2015).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain axis influences microglia development and function > Diverse gut microbiota is a prerequisite for adult microglial maturation and function
What the sources say
- Not checked yetcites Erny et al., 2015 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 39
- Probably not a substantial claim. 11
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A role for the gut microbiome in facilitating microglial maturation and shaping microglial physiology has emerged in recent years.”
§ Microbiome–microglia connections via the gut–brain axis > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
- Rests on an assumption: Environmental factors and mechanisms shaping the developmental, homeostatic, and pathogenic program of microglia remain poorly understood.
In the paper
“Microglial development appears arrested in GF mice, as supported by high expression of genes characteristic of early and premicroglia in microglia from adult GF mice.”
§ Microbiome–microglia connections via the gut–brain axis > Microglia during development and adulthood > Microglia maturation
What the sources say
- Not checked yetcites Erny et al., 2015 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Another microbial metabolite that influences microglia activity is tryptophan, a serotonin precursor.”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation > Bacterial-derived neuroactive substances
What the sources say
- Not checked yetcites Feng et al., 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In female offspring, by contrast, disruption was most notable in adults, and differentially expressed genes were primarily involved in immune and transcriptional signaling (Thion et al., 2018).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain axis influences microglia development and function > Maternal microbiota shapes prenatal microglial maturation and function
What the sources say
- Not checked yetcites Thion et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Once in the circulation, these substances activate a pro-inflammatory immune response mediated by peripheral T cells and macrophages and compromise the integrity of the BBB (Rochfort et al., 2014).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation > Regulation of the intestinal barrier and peripheral immune response
What the sources say
- Not checked yetcites Rochfort et al., 2014 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“SCFAs have been shown to activate sympathetic nervous system activity and alleviate intestinal inflammation, and altered SCFA production has been demonstrated in a variety of neuropathologies such as PD and ASD (Smith et al., 2013; MacFabe, 2015; Unger et al., 2016).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation > Bacterial-derived neuroactive substances
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For example, microglia from E18.5 embryos from GF mothers show an increased density in various brain regions, with increased numbers of microglia exhibiting a ramified morphology, indicative of a resting state.”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain axis influences microglia development and function > Maternal microbiota shapes prenatal microglial maturation and function
What the sources say
- Not checked yetcites Thion et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Approximately 70–80% of immune cells in the human body are found in the gut, allowing for direct gut–immune cell interactions (Vighi et al., 2008).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation > Regulation of the intestinal barrier and peripheral immune response
What the sources say
- Not checked yetcites Vighi et al., 2008 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Vagus nerve stimulation combined with LPS challenge has also been reported to decrease microglial production of the pro-inflammatory cytokines IL-6, IL-1β, and TNFα in the brain, an effect no longer observed following vagotomy (Meneses et al., 2016).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation > The vagus nerve
What the sources say
- Not checked yetcites Meneses et al., 2016 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Metabolism of tryptophan by activated microglia produces the neurotoxin quinolinic acid, an N-methyl-D-aspartate agonist implicated in several neurological conditions including Huntington’s disease and depression (Feng et al., 2017).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation > Bacterial-derived neuroactive substances
What the sources say
- Not checked yetcites Feng et al., 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings suggest that microglia are highly sensitive to perturbations in the gut microbial community during adulthood and require continual input from a complex gut microbiota to maintain homeostasis in the adult.”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain axis influences microglia development and function > Diverse gut microbiota is a prerequisite for adult microglial maturation and function
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“SCFAs can exert physiological effects in the CNS via two primary mechanisms: activation of G protein–coupled receptors (GPCRs) expressed in the liver, spleen, and large intestine and inhibition of histone deacetylases (Kimura et al., 2011; Tan et al., 2014b).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation > Bacterial-derived neuroactive substances
What the sources say
- Not checked yetcites Kimura et al., 2011 source
- Not checked yetcites Tan et al., 2014b
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Among the most abundantly produced SCFAs are acetic acid, propionic acid, and butyric acid, which collectively make up ∼95% of SCFAs synthesized in the gut (Cook and Sellin, 1998).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation > Bacterial-derived neuroactive substances
What the sources say
- Not checked yetcites Cook and Sellin, 1998
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Information about the state of peripheral inflammation and GI health is received in the CNS via vagal afferents that innervate the GI tract and can influence microglial activation and neuroinflammation.”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Altered microglial morphology and density, as well as attenuated inflammatory responses, are also observed in offspring of GF dams immediately after birth, a time when microglia typically exhibit an activated phenotype (Castillo-Ruiz et al., 2018).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain axis influences microglia development and function > Maternal microbiota shapes prenatal microglial maturation and function
What the sources say
- Not checked yetcites Castillo-Ruiz et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The heterogeneity of microglial behavior in response to both intrinsic and extrinsic factors provides further evidence of their complexity, with the gut microbiome representing a key contributing factor in microglial development and function.”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain axis influences microglia development and function > Maternal microbiota shapes prenatal microglial maturation and function
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In male offspring of GF dams, disruption of the transcriptomic profile and morphology of microglia was greatest during the embryonic phase of development, and differentially regulated genes were mostly associated with metabolic and translational pathways (Thion et al., 2018).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain axis influences microglia development and function > Maternal microbiota shapes prenatal microglial maturation and function
What the sources say
- Not checked yetcites Thion et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Short-chain fatty acids (SCFAs) are metabolic byproducts of bacterial dietary fiber fermentation that can enter the systemic circulation and cross the BBB (Conn et al., 1983).”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation > Bacterial-derived neuroactive substances
What the sources say
- Not checked yetcites Conn et al., 1983
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gut–brain communication may influence microglia via two routes: the vagus nerve and the circulatory system.”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fine-tuning of the intestinal barrier by gut microbiota and their interactions with gut immune cells modulates peripheral inflammation and can trigger downstream inflammatory responses in the CNS.”
§ Microbiome–microglia connections via the gut–brain axis > Gut–brain communication pathways: Vagal transmission and systemic circulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“First is the critical role of gut-derived factors in regulating microglial function in the healthy state, which suggests that signals originating from the gut microbiota might also drive a pathogenic microglial phenotype that promotes disease.”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This dysbiosis is potentially sufficient to markedly disrupt microglial function and subsequently facilitate disease pathogenesis.”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These MIA offspring also exhibit increased intestinal permeability and intestinal inflammation, two GI symptoms commonly found in children with ASD (Hsiao et al., 2013; Chaidez et al., 2014).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While this pattern of α-synuclein spreading is not observed in all cases of sporadic PD, vagotomy may be associated with reduced risk of developing PD in humans, potentially implicating peripheral influences on disease development (Svensson et al., 2015; Liu et al., 2017).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similar to its ameliorative effect in colitis, oral administration of Bacteroides fragilis to offspring of MIA mice at weaning rescues the integrity of the intestinal barrier, reduces anxiety, and improves communication and repetitive behaviors (Hsiao et al., 2013).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
What the sources say
- Not checked yetcites Hsiao et al., 2013 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mice lacking the fractalkine receptor Cx3cr1 demonstrate a temporary reduction in the number of microglia during early postnatal development, as well as increased synaptic density, immature brain circuitry, and signal transmission deficits that persist into adulthood (Paolicelli et al., 2011; Zhan et al., 2014).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Pathological hallmarks of PD include death of dopaminergic neurons of the substantia nigra pars compacta and intraneuronal accumulation of the α-synuclein protein (Goedert et al., 2013).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
What the sources say
- Not checked yetcites Goedert et al., 2013 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Postmortem analysis of brain tissue collected from ASD patients show perturbations in microglial immune surveillance and synaptic remodeling, with evidence for heightened microglial activation, including increased expression of MHC II, elevated levels of pro- and anti-inflammatory cytokines, and increased microglial density (Vargas et al., 2005; Morgan et al., 2010; Voineagu et al., 2011; Gupta et”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Studies of ASD and other neurodevelopmental disorders provide evidence for a potential pathogenic role for both dysbiosis and microglial dysfunction, and suggests that microglia may link early-life dysbiosis to long-lasting neurological abnormalities.”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Children with ASD present with a wide range of cognitive and behavioral symptoms, including delayed language development, impaired social and communication skills, and repetitive behavior, depending on where they lie on the spectrum of disease severity (Plauche Johnson, 2004).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
What the sources say
- Not checked yetcites Plauche Johnson, 2004 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“PD is the second most common neurodegenerative disorder and is defined by the presence of motor symptoms including bradykinesia, rigidity, and resting tremor (Postuma et al., 2015).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
What the sources say
- Not checked yetcites Postuma et al., 2015 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Cross-sectional studies comparing the gut microbiota composition between healthy and ASD individuals have revealed an altered microbiota profile in patients with ASD, with several studies reporting increased levels of Clostridium and Lactobacillus along with elevated levels of SCFAs, including propionic and butyric acid (Wang et al., 2012, 2013; De Angelis et al., 2013; Kang et al., 2013).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A complex interplay of genetic and environmental factors is thought to drive the pathogenesis of PD, eventually leading to mitochondrial and autophagic dysfunction (Shulman et al., 2011).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
What the sources say
- Not checked yetcites Shulman et al., 2011 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“While the MIA model has limitations in terms of replicating the complex symptomatology of ASD, the model faithfully recapitulates abnormalities in both microglial behavior and GI function that are frequently observed in patients.”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This in turn could compromise neuronal function and eventually lead to synaptic degeneration and neuronal death.”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Microglia from young MIA offspring show increased expression of inflammation-related genes typically associated with an adult microglial phenotype and down-regulation of genes expressed during earlier developmental stages (e.g., Pu.1 and Irf8), suggesting that maternal inflammation disrupts the timeline of normal microglial maturation (Matcovitch-Natan et al., 2016).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
What the sources say
- Not checked yetcites Matcovitch-Natan et al., 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Given their wide spectrum of physiological functions and myriad roles in development and homeostasis, microglia are believed to be involved in the pathogenesis of several neurodevelopmental and neurodegenerative disorders.”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“While commensal symbiotic bacteria are critical for proper microglial maturation, induction of infection in pregnant dams can have disruptive effects on the progression of microglial development in offspring (Pratt et al., 2013; Matcovitch-Natan et al., 2016; Mattei et al., 2017).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These mice display reduced motor deficits, GI dysfunction, and microglial activation when compared with mice with an intact gut microbiota (Sampson et al., 2016).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
What the sources say
- Not checked yetcites Sampson et al., 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The shift in microbial communities may contribute to the elevated levels of peripheral inflammation and intestinal permeability that are frequently seen in PD patients and might drive misfolding of α-synuclein in the gut and its retrograde propagation to the CNS.”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While interindividual variation is high, PD patients often exhibit increased levels of Enterobacteriaceae and decreased levels of Bacteroidetes and Prevotellaceae (Keshavarzian et al., 2015; Unger et al., 2016).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Feeding these GF transgenic mice a mixture of three SCFAs up-regulated microglial activation and induced motor deficits similar to those observed in colonized animals (Sampson et al., 2016).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
What the sources say
- Not checked yetcites Sampson et al., 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies show altered abundance of certain bacterial strains in patients with PD, changes that may correlate with severity of motor deficits (Scheperjans et al., 2015; Mertsalmi et al., 2017).”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Signals originating from the gut microbiota and transmitted to the brain have the potential to alleviate or exacerbate disease pathogenesis, changes that may operate through gut-mediated changes in microglial behavior.”
§ Microbiome–microglia connections via the gut–brain axis > Future directions and challenges
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
The paper relies on this without support.
Environmental factors and mechanisms shaping the developmental, homeostatic, and pathogenic program of microglia remain poorly understood.
“However, environmental factors and mechanisms shaping the developmental, homeostatic, and pathogenic program of microglia remain poorly understood.”
The paper relies on this without support.
The womb is likely a sterile environment.
“While the womb is likely a sterile environment”
The paper relies on this without support.
BBB-permeable bacterial metabolites, including SCFAs, modulate microglial maturation.
“BBB-permeable bacterial metabolites, including SCFAs, modulate microglial maturation through mechanisms that are yet to be determined.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, gut bacteria can also affect CNS inflammation by binding to specific receptors, such as the proinflammatory tachykinin/neurokinin receptors, in the vagus nerve fiber.104”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [104]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“As alluded to in earlier sections microbiota-microglia interactions are receiving much attention of late as key mechanisms underlying microbiota-immune-brain interactions (Abdel-Haq et al., 2019;Rea et al., 2016;Vuong et al., 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Abdel-Haq et al., 2019
In the citing paper
“Throughout the host lifespan, the gut microbiome provides essential signals to microglia during health and disease.59,60,187,188”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [187]
In the citing paper
“There is increasing evidence that interactions between the gut microbiome and the CNS innate immune system (gut-brain axis) may modulate AD pathogenesis.”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Abdel-Haq et al., 2019
In the citing paper
“Various aspects of CNS physiology are regulated by the microbiome, including microglial maturation and function (Abdel-Haq et al., 2019).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Abdel-Haq et al., 2019
In the citing paper
“Both microbial dysbiosis and microglial dysfunction have been described in several neurological diseases, including behavioral, inflammatory and neurodegenerative disorders.243”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [243]
In the citing paper
“The GM appears to influence microglial development and maturation (120, 121), and animal models have demonstrated downstream effects on various aspects of neurocognitive function (19, 45, 60, 114, 115).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [121]
In the citing paper
“SCFAs may also improve neuronal homeostasis and function by influencing neurotrophic factors such as nerve growth factor, glial cell line-derived neurotrophic factor, and BDNF (119–122).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [121]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease
“Decreased SCFA levels in ASD patients compared to healthy controls.”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > ASD
“several studies reporting increased levels of Clostridium and Lactobacillus along with elevated levels of SCFAs, including propionic and butyric acid”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease
“>80% of PD patients report GI dysfunction (e.g., increased intestinal permeability, constipation, and nausea) 10–20 yr prior to onset of motor symptoms.”
§ Microbiome–microglia connections via the gut–brain axis > Microglial dysfunction and microbial dysbiosis in disease > PD
“Nonmotor symptoms, including chronic constipation and GI distress, precede motor symptoms in up to 80% of PD patients”
Citations
Cites
Diversity of the Human Intestinal Microbial Flora
Eckburg, P. B., Bik, E. M., Bernstein, C. N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S. R., Nelson, K. E., & Relman, D. A. (2005) · Science · doi:10.1126/science.1110591 · Cited by 7,913 · cited 1×
“By the age of 5, the gut microbiota stabilizes and begins to resemble that of an adult, with members of Bacteroidetes and Firmicutes becoming most abundant (Eckburg et al., 2005).”
BackgroundMDS clinical diagnostic criteria for Parkinson’s disease
Postuma, R. B., Berg, D., Stern, M., Poewe, W., Olanow, C. W., Oertel, W., Obeso, J., Marek, K., Litvan, I., Lang, A. E., et al. (2015) · Movement Disorders · doi:10.1002/mds.26424 · Cited by 7,653
The gut microbiota as an environmental factor that regulates fat storage
Bäckhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., Semenkovich, C. F., & Gordon, J. I. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407076101 · Cited by 6,245 · cited 1×
“Along with preserving the integrity of the intestinal–epithelial barrier along the gastrointestinal (GI) tract, gut bacteria are critical for the development and maturation of the host’s innate and adaptive immune systems, nutrient absorption, host metabolism, and protection against foreign invaders (Hooper et al., 20…”
BackgroundResting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827 · cited 3×
“Under steady-state conditions, surveying microglia have a ramified morphology with a small cell body and many long extended processes that are used to continuously scan and assess the health of cells in close proximity—a process critical for maintaining homeostasis in the absence of pathology (Nimmerjahn et al., 2005;…”
BackgroundA Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493
The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T reg Cell Homeostasis
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413 · cited 1×
“SCFAs have been shown to activate sympathetic nervous system activity and alleviate intestinal inflammation, and altered SCFA production has been demonstrated in a variety of neuropathologies such as PD and ASD (Smith et al., 2013; MacFabe, 2015; Unger et al., 2016).”
BackgroundFate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175 · cited 3×
“The maturation and differentiation of erythromyeloid progenitors into microglia within the yolk sac requires several transcription factors, including RUNX1, JUN, PU.1, and IRF8, the expression of which coincides with that of microglial markers, including CX3CR1, CD11b, and F4/80 (Ginhoux et al., 2010; Matcovitch-Natan…”
BackgroundDominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N., & Knight, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002601107 · Cited by 4,774 · cited 1×
“Initial microbial colonization of the gut happens at birth and is heavily influenced by the mode of delivery (cesarean section versus vaginal birth; Dominguez-Bello et al., 2010; Rodríguez et al., 2015).”
BackgroundMacrophage biology in development, homeostasis and disease
Wynn, T. A., Chawla, A., & Pollard, J. W. (2013) · Nature · doi:10.1038/nature12034 · Cited by 4,684 · cited 1×
“During early development, microglia actively regulate neuronal cell numbers and synaptic refinement, ultimately shaping neural circuitry (Sierra et al., 2010; Paolicelli et al., 2011; Wynn et al., 2013).”
BackgroundMeta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244 · cited 3×
“Microglia also play a role in establishing and shaping neural circuitry during postnatal stages of development, which has implications for cognitive function and social behavior (Paolicelli et al., 2011).”
BackgroundVagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
Borovikova, L. V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G. I., Watkins, L. R., Wang, H., Abumrad, N., Eaton, J. W., & Tracey, K. J. (2000) · Nature · doi:10.1038/35013070 · Cited by 4,211 · cited 1×
“In addition to interacting with gut microbes, vagal nerves interact extensively with different components of the peripheral immune system, continuously monitoring the inflammatory state of the gut (Borovikova et al., 2000; Miao et al., 2004).”
BackgroundMicroglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · cited 1×
“In a remarkable parallel to macrophage recognition of pathogens, this process has been shown to depend on several complement proteins (C1q and C3) that tag extraneous synapses for microglial engulfment (Stevens et al., 2007; Schafer et al., 2012).”
BackgroundATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913 · cited 1×
“To sustain brain homeostasis, microglia constantly survey their microenvironment through the dynamic extension and retraction of their processes (Davalos et al., 2005; Nimmerjahn et al., 2005).”
BackgroundBravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J., & Cryan, J. F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102999108 · Cited by 3,888 · cited 1×
“Indeed, the anxiolytic effects of administration of the probiotic species Lactobacillus rhamnosus and Bifidobacterium longum is absent in vagotomized mice, providing strong evidence that gut–vagal nerve interactions regulate social behavior (Wang et al., 2002; Bercik et al., 2011; Bravo et al., 2011).”
BackgroundGut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.018 · Cited by 3,622 · cited 1×
“Second, dysbiosis is observed in several neurological conditions in which microglial dysfunction is thought to be a contributing factor to disease development, including ASD and PD (Table 1; Hsiao et al., 2013; Sampson et al., 2016).”
BackgroundSelf-citationIndigenous bacteria from the gut microbiota regulate host serotonin biosynthesis
Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015) · Cell · doi:10.1016/j.cell.2015.02.047 · Cited by 3,614 · cited 1×
“Circulation of microbe-derived neurotransmitters, including acetylcholine (Lactobacillus), GABA (Bifidobacteria and Lactobacillus), and serotonin (Enterococcus and Streptococcus), can potentially influence microglial activation through direct and indirect means (Komatsuzaki et al., 2005; Yano et al., 2015; Pokusaeva e…”
BackgroundSelf-citationHost microbiota constantly control maturation and function of microglia in the CNS
Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4030 · Cited by 3,569 · cited 7×
“With the exception of indiscernible differences in microglial density, microglia isolated from antibiotic-treated SPF mice exhibit a microglial gene expression profile and morphology nearly identical to those derived from GF mice (Erny et al., 2015; Thion et al., 2018).”
BackgroundInfluentialComplement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343
The Classical Complement Cascade Mediates CNS Synapse Elimination
Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., Micheva, K. D., Mehalow, A. K., Huberman, A. D., Stafford, B., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.036 · Cited by 3,313 · cited 1×
“In a remarkable parallel to macrophage recognition of pathogens, this process has been shown to depend on several complement proteins (C1q and C3) that tag extraneous synapses for microglial engulfment (Stevens et al., 2007; Schafer et al., 2012).”
BackgroundHsiao, E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., Codelli, J. A., Chow, J., Reisman, S. E., Petrosino, J. F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.024 · Cited by 3,283 · cited 3×
“Similar to its ameliorative effect in colitis, oral administration of Bacteroides fragilis to offspring of MIA mice at weaning rescues the integrity of the intestinal barrier, reduces anxiety, and improves communication and repetitive behaviors (Hsiao et al., 2013).”
BackgroundSelf-citationNicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation
Wang, H., Yu, M., Ochani, M., Amella, C. A., Tanovic, M., Susarla, S., Li, J. H., Wang, H., Yang, H., Ulloa, L., et al. (2003) · Nature · doi:10.1038/nature01339 · Cited by 3,228 · cited 1×
“Concurrently, vagal efferent nerves relay information about the immune status of the brain back to the gut, with increased CNS inflammation feeding back to inhibit further release of peripheral pro-inflammatory cytokines through acetylcholine-mediated signaling (Wang et al., 2003; Goehler et al., 2005).”
BackgroundNormal gut microbiota modulates brain development and behavior
Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibberd, M. L., Forssberg, H., & Pettersson, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010529108 · Cited by 3,228
McGeer, P. L., Itagaki, S., Boyes, B. E., & McGeer, E. G. (1988) · Neurology · doi:10.1212/wnl.38.8.1285 · Cited by 2,990
Development of the Human Infant Intestinal Microbiota
Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A., & Brown, P. O. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050177 · Cited by 2,877 · cited 1×
“In the first few years of life, the gut microbiota is relatively less diverse and less stable compared with that of adults, with an abundance of Proteobacteria and Actinobacteria (Palmer et al., 2007; Rodríguez et al., 2015).”
BackgroundSynaptic, transcriptional and chromatin genes disrupted in autism
Study, T. D., De Rubeis, S., Autism, H. M. C. F., UK10K Consortium, The Autism Sequencing Consortium, He, X., Goldberg, A. P., Poultney, C. S., Samocha, K., Ercument Cicek, A., et al. (2014) · Nature · doi:10.1038/nature13772 · Cited by 2,746
The NHGRI GWAS Catalog, a curated resource of SNP-trait associations
Welter, D., MacArthur, J., Morales, J., Burdett, T., Hall, P., Junkins, H., Klemm, A., Flicek, P., Manolio, T., Hindorff, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1229 · Cited by 2,707
Stages in the development of Parkinson’s disease-related pathology
Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., & Del Tredici, K. (2004) · Cell and Tissue Research · doi:10.1007/s00441-004-0956-9 · Cited by 2,689
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543 · cited 1×
“The adult microglia transcriptome overlaps with, but is distinct from, other tissue-resident macrophages and is characterized by expression of microglial-specific markers, including Sall1, P2ry12, Gpr84, and Tmem119 (Hickman et al., 2013; Butovsky et al., 2014; Gosselin et al., 2014; Matcovitch-Natan et al., 2016).”
BackgroundDevelopment, maintenance and disruption of the blood-brain barrier
Obermeier, B., Daneman, R., & Ransohoff, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3407 · Cited by 2,452 · cited 1×
“This process of brain colonization precedes the formation of the BBB, which eventually shields microglia from potentially toxic peripheral influences throughout both fetal development and adulthood (Obermeier et al., 2013).”
BackgroundThe role of short chain fatty acids in health and disease
Tan, J., McKenzie, C., Potamitis, M., Thorburn, A. N., Mackay, C. R., & Macia, L. (2014) · Advances in immunology · doi:10.1016/b978-0-12-800100-4.00003-9 · Cited by 2,425 · cited 3×
“McGeer et al., 1988; Akiyama and McGeer, 1989; Gerhard et al., 2006; Kim and Joh, 2006; Watson et al., 2012; Fasano et al., 2013; Tan et al., 2014a; Keshavarzian et al., 2015; Scheperjans et al., 2015; Machado et al., 2016; Poirier et al., 2016; Sampson et al., 2016; Unger et al., 2016; Zhang et…”
BackgroundInfluentialSchizophrenia risk from complex variation of complement component 4
Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., Tooley, K., Presumey, J., Baum, M., Van Doren, V., et al. (2016) · Nature · doi:10.1038/nature16549 · Cited by 2,394
Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors
Gomez Perdiguero, E., Klapproth, K., Schulz, C., Busch, K., Azzoni, E., Crozet, L., Garner, H., Trouillet, C., de Bruijn, M. F., Geissmann, F., et al. (2015) · Nature · doi:10.1038/nature13989 · Cited by 2,339
Molecular Analysis of Commensal Host-Microbial Relationships in the Intestine
Hooper, L. V., Wong, M. H., Thelin, A., Hansson, L., Falk, P. G., & Gordon, J. I. (2001) · Science · doi:10.1126/science.291.5505.881 · Cited by 2,202 · cited 1×
“Along with preserving the integrity of the intestinal–epithelial barrier along the gastrointestinal (GI) tract, gut bacteria are critical for the development and maturation of the host’s innate and adaptive immune systems, nutrient absorption, host metabolism, and protection against foreign invaders (Hooper et al., 20…”
BackgroundDifferential Roles of M1 and M2 Microglia in Neurodegenerative Diseases
Tang, Y., & Le, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-9070-5 · Cited by 2,190 · cited 1×
“, nitric oxide and reactive oxygen species) into their surrounding environment to suppress and fight off invading pathogens (Franco and Fernández-Suárez, 2015; Tang and Le, 2016).”
BackgroundNeuroglial activation and neuroinflammation in the brain of patients with autism
Vargas, D. L., Nascimbene, C., Krishnan, C., Zimmerman, A. W., & Pardo, C. A. (2005) · Annals of Neurology · doi:10.1002/ana.20315 · Cited by 2,149 · cited 2×
“Postmortem analysis of brain tissue collected from ASD patients show perturbations in microglial immune surveillance and synaptic remodeling, with evidence for heightened microglial activation, including increased expression of MHC II, elevated levels of pro- and anti-inflammatory cytokines, and increased microglial d…”
BackgroundGut microbiota are related to Parkinson's disease and clinical phenotype
Scheperjans, F., Aho, V., Pereira, P. A. B., Koskinen, K., Paulin, L., Pekkonen, E., Haapaniemi, E., Kaakkola, S., Eerola‐Rautio, J., Pohja, M., et al. (2015) · Movement Disorders · doi:10.1002/mds.26069 · Cited by 1,968
Interactions between the microbiota, immune and nervous systems in health and disease
Fung, T. C., Olson, C. A., & Hsiao, E. Y. (2017) · Nature Neuroscience · doi:10.1038/nn.4476 · Cited by 1,900 · cited 3×
“Sophisticated crosstalk between the CNS and the gut microbiome (known as the gut–brain axis) is critical for several facets of CNS physiology, including microglial development and function (Mayer et al., 2015; Fung et al., 2017).”
BackgroundLloyd-Price, J., Abu-Ali, G., & Huttenhower, C. (2016) · Genome Medicine · doi:10.1186/s13073-016-0307-y · Cited by 1,891 · cited 1×
“The ∼100 trillion microorganisms that reside in the digestive tract, and the wide assortment of metabolites they produce, are critical for maintaining health (Lloyd-Price et al., 2016).”
BackgroundTranscriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology
Voineagu, I., Wang, X., Johnston, P., Lowe, J. K., Tian, Y., Horvath, S., Mill, J., Cantor, R. M., Blencowe, B. J., & Geschwind, D. H. (2011) · Nature · doi:10.1038/nature10110 · Cited by 1,874 · cited 1×
“Postmortem analysis of brain tissue collected from ASD patients show perturbations in microglial immune surveillance and synaptic remodeling, with evidence for heightened microglial activation, including increased expression of MHC II, elevated levels of pro- and anti-inflammatory cytokines, and increased microglial d…”
BackgroundNew tools for studying microglia in the mouse and human CNS
Bennett, M. L., Bennett, F. C., Liddelow, S. A., Ajami, B., Zamanian, J. L., Fernhoff, N. B., Mulinyawe, S. B., Bohlen, C. J., Adil, A., Tucker, A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525528113 · Cited by 1,804
Microglia emerge as central players in brain disease
Salter, M. W., & Stevens, B. (2017) · Nature Medicine · doi:10.1038/nm.4397 · Cited by 1,767 · cited 1×
“In addition to important roles in brain development and homeostasis, recent genetic studies provide evidence that microglia contribute to the pathogenesis of several neurodegenerative and neurodevelopmental disorders (Salter and Stevens, 2017).”
BackgroundMeta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects
Miller, B. J., Buckley, P., Seabolt, W., Mellor, A., & Kirkpatrick, B. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.04.013 · Cited by 1,742
Microglia Shape Adult Hippocampal Neurogenesis through Apoptosis-Coupled Phagocytosis
Sierra, A., Encinas, J. M., Deudero, J. J. P., Chancey, J. H., Enikolopov, G., Overstreet-Wadiche, L. S., Tsirka, S. E., & Maletic-Savatic, M. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.014 · Cited by 1,622 · cited 2×
“During early development, microglia actively regulate neuronal cell numbers and synaptic refinement, ultimately shaping neural circuitry (Sierra et al., 2010; Paolicelli et al., 2011; Wynn et al., 2013).”
BackgroundThe Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota
Round, J. L., Lee, S. M., Li, J., Tran, G., Jabri, B., Chatila, T. A., & Mazmanian, S. K. (2011) · Science · doi:10.1126/science.1206095 · Cited by 1,604 · cited 1×
“Along with preserving the integrity of the intestinal–epithelial barrier along the gastrointestinal (GI) tract, gut bacteria are critical for the development and maturation of the host’s innate and adaptive immune systems, nutrient absorption, host metabolism, and protection against foreign invaders (Hooper et al., 20…”
BackgroundSelf-citationMicroglial interactions with synapses are modulated by visual experience
Tremblay, M.-È., Lowery, R. L., & Majewska, A. K. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000527 · Cited by 1,542 · cited 1×
“Furthermore, high-resolution microscopy has confirmed a physical, albeit transient, interaction between microglia and synapses on neighboring neurons (Tremblay et al., 2010).”
BackgroundThe microglial sensome revealed by direct RNA sequencing
Hickman, S. E., Kingery, N. D., Ohsumi, T. K., Borowsky, M. L., Wang, L.-C., Means, T. K., & El Khoury, J. (2013) · Nature Neuroscience · doi:10.1038/nn.3554 · Cited by 1,511 · cited 1×
“The adult microglia transcriptome overlaps with, but is distinct from, other tissue-resident macrophages and is characterized by expression of microglial-specific markers, including Sall1, P2ry12, Gpr84, and Tmem119 (Hickman et al., 2013; Butovsky et al., 2014; Gosselin et al., 2014; Matcovitch-Natan et al., 2016).”
BackgroundGut/brain axis and the microbiota
Mayer, E. A., Tillisch, K., & Gupta, A. (2015) · Journal of Clinical Investigation · doi:10.1172/jci76304 · Cited by 1,503
Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways
Kierdorf, K., Erny, D., Goldmann, T., Sander, V., Schulz, C., Perdiguero, E. G., Wieghofer, P., Heinrich, A., Riemke, P., Hölscher, C., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3318 · Cited by 1,457
The relation between inflammation and neurodegeneration in multiple sclerosis brains
Frischer, J. M., Bramow, S., Dal-Bianco, A., Lucchinetti, C. F., Rauschka, H., Schmidbauer, M., Laursen, H., Sorensen, P. S., & Lassmann, H. (2009) · Brain · doi:10.1093/brain/awp070 · Cited by 1,450
The composition of the gut microbiota throughout life, with an emphasis on early life
Rodríguez, J. M., Murphy, K., Stanton, C., Ross, R. P., Kober, O. I., Juge, N., Avershina, E., Rudi, K., Narbad, A., Jenmalm, M. C., et al. (2015) · Microbial Ecology in Health and Disease · doi:10.3402/mehd.v26.26050 · Cited by 1,414 · cited 2×
“Initial microbial colonization of the gut happens at birth and is heavily influenced by the mode of delivery (cesarean section versus vaginal birth; Dominguez-Bello et al., 2010; Rodríguez et al., 2015).”
BackgroundNeufeld, K. M., Kang, N., Bienenstock, J., & Foster, J. A. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2010.01620.x · Cited by 1,392 · cited 2×
“, lacking all commensal and pathogenic microbes) mice, antibiotics, fecal microbiota transplant (FMT), and pre-/probiotics have demonstrated a role for gut bacteria in neurotransmitter signaling, synaptic plasticity, myelination, and neurogenesis (Diaz Heijtz et al., 2011; Neufeld et al., 2011; Ogbonnaya et al., 2015;…”
BackgroundProinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis
Lee, Y. K., Menezes, J. S., Umesaki, Y., & Mazmanian, S. K. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000082107 · Cited by 1,323
Self-citationGosselin, D., Link, V. M., Romanoski, C. E., Fonseca, G. J., Eichenfield, D. Z., Spann, N. J., Stender, J. D., Chun, H. B., Garner, H., Geissmann, F., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.023 · Cited by 1,307 · cited 1×
“The adult microglia transcriptome overlaps with, but is distinct from, other tissue-resident macrophages and is characterized by expression of microglial-specific markers, including Sall1, P2ry12, Gpr84, and Tmem119 (Hickman et al., 2013; Butovsky et al., 2014; Gosselin et al., 2014; Matcovitch-Natan et al., 2016).”
BackgroundSelf-citationColonic bacterial composition in Parkinson's disease
Keshavarzian, A., Green, S. J., Engen, P. A., Voigt, R. M., Naqib, A., Forsyth, C. B., Mutlu, E., & Shannon, K. M. (2015) · Movement Disorders · doi:10.1002/mds.26307 · Cited by 1,281
Zhang, W., Wang, T., Pei, Z., Miller, D. S., Wu, X., Block, M. L., Wilson, B., Zhang, W., Zhou, Y., Hong, J.-S., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-2751com · Cited by 1,265
Zhan, Y., Paolicelli, R. C., Sforazzini, F., Weinhard, L., Bolasco, G., Pagani, F., Vyssotski, A. L., Bifone, A., Gozzi, A., Ragozzino, D., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3641 · Cited by 1,236 · cited 2×
“Abnormal neural circuitry due to the absence of microglia during a critical window of brain development in these mice is associated with behavioral deficits similar to those seen in individuals with ASD (Zhan et al., 2014).”
BackgroundAn environment-dependent transcriptional network specifies human microglia identity
Gosselin, D., Skola, D., Coufal, N. G., Holtman, I. R., Schlachetzki, J. C. M., Sajti, E., Jaeger, B. N., O’Connor, C., Fitzpatrick, C., Pasillas, M. P., et al. (2017) · Science · doi:10.1126/science.aal3222 · Cited by 1,220
Self-citationIn vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease
Gerhard, A., Pavese, N., Hotton, G., Turkheimer, F., Es, M., Hammers, A., Eggert, K., Oertel, W., Banati, R. B., & Brooks, D. J. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.08.002 · Cited by 1,200
Goedert, M., Spillantini, M. G., Del Tredici, K., & Braak, H. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.242 · Cited by 1,190
Microglia development follows a stepwise program to regulate brain homeostasis
Matcovitch-Natan, O., Winter, D. R., Giladi, A., Vargas Aguilar, S., Spinrad, A., Sarrazin, S., Ben-Yehuda, H., David, E., Zelada González, F., Perrin, P., et al. (2016) · Science · doi:10.1126/science.aad8670 · Cited by 1,180 · cited 9×
“The adult microglia transcriptome overlaps with, but is distinct from, other tissue-resident macrophages and is characterized by expression of microglial-specific markers, including Sall1, P2ry12, Gpr84, and Tmem119 (Hickman et al., 2013; Butovsky et al., 2014; Gosselin et al., 2014; Matcovitch-Natan et al., 2016).”
BackgroundInfluentialMicrobial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring
Buffington, S. A., Di Prisco, G. V., Auchtung, T. A., Ajami, N. J., Petrosino, J. F., & Costa-Mattioli, M. (2016) · Cell · doi:10.1016/j.cell.2016.06.001 · Cited by 1,163 · cited 1×
“Similarly, provision of Lactobacillus reuteri to offspring of dams fed a high-fat diet attenuates their social deficits, further supporting a role for the gut microbiota in influencing outcomes of neurodevelopmental disorders (Buffington et al., 2016).”
BackgroundUnger, M. M., Spiegel, J., Dillmann, K.-U., Grundmann, D., Philippeit, H., Bürmann, J., Faßbender, K., Schwiertz, A., & Schäfer, K.-H. (2016) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2016.08.019 · Cited by 1,159 · cited 1×
“SCFAs have been shown to activate sympathetic nervous system activity and alleviate intestinal inflammation, and altered SCFA production has been demonstrated in a variety of neuropathologies such as PD and ASD (Smith et al., 2013; MacFabe, 2015; Unger et al., 2016).”
BackgroundHoeffel, G., Chen, J., Lavin, Y., Low, D., Almeida, F. F., See, P., Beaudin, A. E., Lum, J., Low, I., Forsberg, E. C., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.03.011 · Cited by 1,135
Microglial priming in neurodegenerative disease
Perry, V. H., & Holmes, C. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.38 · Cited by 1,127 · cited 1×
“In each case, there is evidence of immune activation, suggesting a role for microglia-driven inflammation as an etiologic factor (Perry and Holmes, 2014; Norden et al., 2015).”
BackgroundBailey, M. T., Dowd, S. E., Galley, J. D., Hufnagle, A. R., Allen, R. G., & Lyte, M. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.10.023 · Cited by 1,123
Kelly, J. R., Kennedy, P. J., Cryan, J. F., Dinan, T. G., Clarke, G., & Hyland, N. P. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00392 · Cited by 1,110 · cited 1×
“Decreased strength of the intestinal barrier due to dysbiosis and other factors permits entry of pathogenic, immune-stimulating, and neuroactive substances into the systemic circulation (Kelly et al., 2015).”
BackgroundKimura, I., Inoue, D., Maeda, T., Hara, T., Ichimura, A., Miyauchi, S., Kobayashi, M., Hirasawa, A., & Tsujimoto, G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016088108 · Cited by 1,106 · cited 1×
“SCFAs can exert physiological effects in the CNS via two primary mechanisms: activation of G protein–coupled receptors (GPCRs) expressed in the liver, spleen, and large intestine and inhibition of histone deacetylases (Kimura et al., 2011; Tan et al., 2014b).”
BackgroundMicroglial cell origin and phenotypes in health and disease
Saijo, K., & Glass, C. K. (2011) · Nature Reviews Immunology · doi:10.1038/nri3086 · Cited by 1,100
Self-citationMicroglial control of astrocytes in response to microbial metabolites
Rothhammer, V., Borucki, D. M., Tjon, E. C., Takenaka, M. C., Chao, C.-C., Ardura-Fabregat, A., de Lima, K. A., Gutiérrez-Vázquez, C., Hewson, P., Staszewski, O., et al. (2018) · Nature · doi:10.1038/s41586-018-0119-x · Cited by 1,051 · cited 1×
“In a recent study using the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, peripheral metabolism of dietary tryptophan by the gut microbiota was shown to generate metabolites that dampen the ability of microglia to induce pro-inflammatory responses in astrocytes, thereby ameliorating disease (Rothh…”
BackgroundCekanaviciute, E., Yoo, B. B., Runia, T. F., Debelius, J. W., Singh, S., Nelson, C., Kanner, R., Bencosme, Y., Lee, Y. K., Hauser, S. L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1711235114 · Cited by 1,040
Self-citationBercik, P., Park, A. J., Sinclair, D., Khoshdel, A., Lu, J., Huang, X., Deng, Y., Blennerhassett, P. A., Fahnestock, M., Moine, D., et al. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2011.01796.x · Cited by 1,018
Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children
Kang, D.-W., Park, J. G., Ilhan, Z. E., Wallstrom, G., LaBaer, J., Adams, J. B., & Krajmalnik-Brown, R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068322 · Cited by 976
Microglia Regulate the Number of Neural Precursor Cells in the Developing Cerebral Cortex
Cunningham, C. L., Martínez-Cerdeño, V., & Noctor, S. C. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3441-12.2013 · Cited by 976 · cited 1×
“During the early stages of brain development, early microglia and premicroglia phagocytose excess neurons and release neurotrophic and neurotoxic factors, thereby controlling the relative ratio of neurogenesis to apoptosis to ensure that numbers of neurons are maintained within a defined range (Sierra et al., 2010; Cu…”
BackgroundDepression as a Microglial Disease
Yirmiya, R., Rimmerman, N., & Reshef, R. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.001 · Cited by 944
Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota
Harach, T., Marungruang, N., Duthilleul, N., Cheatham, V., Mc Coy, K. D., Frisoni, G., Neher, J. J., Fåk, F., Jucker, M., Lasser, T., et al. (2017) · Scientific Reports · doi:10.1038/srep41802 · Cited by 901
De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D. I., Cristofori, F., Guerzoni, M. E., Gobbetti, M., & Francavilla, R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076993 · Cited by 887
Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain
Alliot, F., Godin, I., & Pessac, B. (1999) · Developmental Brain Research · doi:10.1016/s0165-3806(99)00113-3 · Cited by 884
Hill‐Burns, E. M., Debelius, J. W., Morton, J. T., Wissemann, W. T., Lewis, M. R., Wallen, Z. D., Peddada, S. D., Factor, S. A., Molho, E., Zabetian, C. P., et al. (2017) · Movement Disorders · doi:10.1002/mds.26942 · Cited by 874
Intestinal Bacterial Colonization Induces Mutualistic Regulatory T Cell Responses
Geuking, M. B., Cahenzli, J., Lawson, M. A. E., Ng, D. C. K., Slack, E., Hapfelmeier, S., McCoy, K. D., & Macpherson, A. J. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.021 · Cited by 840 · cited 1×
“Along with preserving the integrity of the intestinal–epithelial barrier along the gastrointestinal (GI) tract, gut bacteria are critical for the development and maturation of the host’s innate and adaptive immune systems, nutrient absorption, host metabolism, and protection against foreign invaders (Hooper et al., 20…”
BackgroundMiyake, S., Kim, S., Suda, W., Oshima, K., Nakamura, M., Matsuoka, T., Chihara, N., Tomita, A., Sato, W., Kim, S.-W., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137429 · Cited by 809
Vagotomy and subsequent risk of Parkinson's disease
Svensson, E., Horváth‐Puhó, E., Thomsen, R. W., Djurhuus, J. C., Pedersen, L., Borghammer, P., & Sørensen, H. T. (2015) · Annals of Neurology · doi:10.1002/ana.24448 · Cited by 806
Parkinson’s disease: genetics and pathogenesis
Shulman, J. M., De Jager, P. L., & Feany, M. B. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130242 · Cited by 801
Layer V cortical neurons require microglial support for survival during postnatal development
Ueno, M., Fujita, Y., Tanaka, T., Nakamura, Y., Kikuta, J., Ishii, M., & Yamashita, T. (2013) · Nature Neuroscience · doi:10.1038/nn.3358 · Cited by 781 · cited 1×
“In addition to dictating neuronal density, microglia supply a steady stream of neurotrophic factors (such as nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], and insulin-like growth factor 1 [IGF-1]) that promote neuronal survival and differentiation of neural progenitors (Gomes et al., 2013; Ueno…”
BackgroundMicrobiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner
Thion, M. S., Low, D., Silvin, A., Chen, J., Grisel, P., Schulte-Schrepping, J., Blecher, R., Ulas, T., Squarzoni, P., Hoeffel, G., et al. (2018) · Cell · doi:10.1016/j.cell.2017.11.042 · Cited by 779 · cited 6×
“In male offspring of GF dams, disruption of the transcriptomic profile and morphology of microglia was greatest during the embryonic phase of development, and differentially regulated genes were mostly associated with metabolic and translational pathways (Thion et al., 2018).”
BackgroundInfluentialMorgan, J. T., Chana, G., Pardo, C. A., Achim, C., Semendeferi, K., Buckwalter, J., Courchesne, E., & Everall, I. P. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.024 · Cited by 749
Transcriptomic analysis of purified human cortical microglia reveals age-associated changes
Galatro, T. F., Holtman, I. R., Lerario, A. M., Vainchtein, I. D., Brouwer, N., Sola, P. R., Veras, M. M., Pereira, T. F., Leite, R. E. P., Möller, T., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4597 · Cited by 741
Turner, M. R., Cagnin, A., Turkheimer, F. E., Miller, C. C. J., Shaw, C. E., Brooks, D. J., Leigh, P. N., & Banati, R. B. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.12.012 · Cited by 737
Sun, M.-F., Zhu, Y.-L., Zhou, Z.-L., Jia, X.-B., Xu, Y.-D., Yang, Q., Cui, C., & Shen, Y.-Q. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.02.005 · Cited by 736
Beers, D. R., Henkel, J. S., Xiao, Q., Zhao, W., Wang, J., Yen, A. A., Siklos, L., McKercher, S. R., & Appel, S. H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607423103 · Cited by 733
Experimental autoimmune encephalomyelitis repressed by microglial paralysis
Heppner, F. L., Greter, M., Marino, D., Falsig, J., Raivich, G., Hövelmeyer, N., Waisman, A., Rülicke, T., Prinz, M., Priller, J., et al. (2005) · Nature Medicine · doi:10.1038/nm1177 · Cited by 732
Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain
Askew, K., Li, K., Olmos-Alonso, A., Garcia-Moreno, F., Liang, Y., Richardson, P., Tipton, T., Chapman, M. A., Riecken, K., Beccari, S., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.041 · Cited by 726 · cited 1×
“Once in the brain, microglia are broadly distributed at varying densities and maintain a stable rate of proliferation depending on the stage of host development (Askew et al., 2017).”
BackgroundThe composition of the gut microbiota shapes the colon mucus barrier
Jakobsson, H. E., Rodríguez‐Piñeiro, A. M., Schütte, A., Ermund, A., Boysen, P., Bemark, M., Sommer, F., Bäckhed, F., Hansson, G. C., & Johansson, M. E. (2015) · The EMBO Reports · doi:10.15252/embr.201439263 · Cited by 700 · cited 1×
“Regulation of the intestinal barrier and peripheral immune response The presence of bacteria along the GI tract is critical for the maintenance of the intestinal barrier, which facilitates the exchange of nutrients, water, and electrolytes and prevents the passage of harmful substances and pathogens from the intestina…”
BackgroundMaternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring
Kim, S., Kim, H., Yim, Y. S., Ha, S., Atarashi, K., Tan, T. G., Longman, R. S., Honda, K., Littman, D. R., Choi, G. B., et al. (2017) · Nature · doi:10.1038/nature23910 · Cited by 678 · cited 1×
“Provision of IL-17 promoting segmented filamentous bacteria to MIA mothers further enhances behavioral abnormities in MIA offspring (Kim et al., 2017).”
BackgroundKarczewski, J., Troost, F. J., Konings, I., Dekker, J., Kleerebezem, M., Brummer, R.-J. M., & Wells, J. M. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00327.2009 · Cited by 676 · cited 1×
“20180794 46 gut microbiota can fine-tune the level of intestinal permeability (Karczewski et al., 2010; Alaish et al., 2013).”
BackgroundAlternatively activated microglia and macrophages in the central nervous system
Franco, R., & Fernández‐Suárez, D. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.05.003 · Cited by 674
Sex differences in microglial colonization of the developing rat brain
Schwarz, J. M., Sholar, P. W., & Bilbo, S. D. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07630.x · Cited by 672 · cited 1×
“These trends might help to explain the inherent functional differences in microglia from intact male versus female mice, as well as the sex variations in incidence rates of several neurological disorders (Schwarz et al., 2012; Hanamsagar et al., 2015).”
BackgroundMalkova, N. V., Yu, C. Z., Hsiao, E. Y., Moore, M. J., & Patterson, P. H. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.01.011 · Cited by 662 · cited 1×
“In the MIA model, offspring of mice injected with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic viral mimic that activates TLR3, demonstrate core symptoms of ASD, including repetitive behaviors, communication deficits, and decreased sociability (Malkova et al., 2012).”
MethodNeuroinflammation in Parkinson's disease
Hirsch, E. C., Vyas, S., & Hunot, S. (2012) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(11)70065-7 · Cited by 657 · cited 1×
“In addition to their innate immune and homeostatic functions, microglia have been implicated in the pathogenesis of a broad spectrum of neurodegenerative and behavioral diseases, including PD, Alzheimer’s disease (AD), multiple sclerosis (MS), schizophrenia, and ASD (Vargas et al., 2005; Hirsch et al., 2012; Frick et…”
BackgroundKim, Y. S., & Joh, T. H. (2006) · Experimental & Molecular Medicine · doi:10.1038/emm.2006.40 · Cited by 655
Minter, M. R., Zhang, C., Leone, V., Ringus, D. L., Zhang, X., Oyler-Castrillo, P., Musch, M. W., Liao, F., Ward, J. F., Holtzman, D. M., et al. (2016) · Scientific Reports · doi:10.1038/srep30028 · Cited by 655
Regulation of prefrontal cortex myelination by the microbiota
Hoban, A. E., Stilling, R. M., Ryan, F. J., Shanahan, F., Dinan, T. G., Claesson, M. J., Clarke, G., & Cryan, J. F. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.42 · Cited by 635 · cited 1×
“, lacking all commensal and pathogenic microbes) mice, antibiotics, fecal microbiota transplant (FMT), and pre-/probiotics have demonstrated a role for gut bacteria in neurotransmitter signaling, synaptic plasticity, myelination, and neurogenesis (Diaz Heijtz et al., 2011; Neufeld et al., 2011; Ogbonnaya et al., 2015;…”
BackgroundReview article: short chain fatty acids in health and disease
Cook, & Sellin (1998) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.1998.00337.x · Cited by 633 · cited 1×
“Among the most abundantly produced SCFAs are acetic acid, propionic acid, and butyric acid, which collectively make up ∼95% of SCFAs synthesized in the gut (Cook and Sellin, 1998).”
BackgroundLuczynski, P., McVey Neufeld, K.-A., Oriach, C. S., Clarke, G., Dinan, T. G., & Cryan, J. F. (2016) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw020 · Cited by 632 · cited 1×
“Additionally, the absence of gut microbes causes deficits in cognition and social interaction, further supporting the role of gut microbes in higher-order brain functioning (Neufeld et al., 2011; Luczynski et al., 2016).”
BackgroundNeocortical glial cell numbers in human brains
Pelvig, D. P., Pakkenberg, H., Stark, A. K., & Pakkenberg, B. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.04.013 · Cited by 601 · cited 1×
“Introduction Microglia are tissue-resident macrophages that make up ∼5–15% of total brain cells and have several well-defined functions in the central nervous system (CNS; Pelvig et al., 2008).”
BackgroundBrites, D., & Fernandes, A. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00476 · Cited by 599
Vagal pathways for microbiome-brain-gut axis communication
Forsythe, P., Bienenstock, J., & Kunze, W. A. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_5 · Cited by 576 · cited 2×
“Communication through the vagus nerve is essential for signals mediating satiety, stress, and mood, and these signals are governed by changes in enteric neuron activity and the behavior of gut microbes (Goehler et al., 2005; Forsythe et al., 2014; Browning et al., 2017).”
BackgroundHenry, C. J., Huang, Y., Wynne, A. M., & Godbout, J. P. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.09.002 · Cited by 565 · cited 1×
“Indeed, increased intestinal inflammation driven by either LPS or bacterial infection correlates with elevated levels of microglial activation and release of pro-inflammatory cytokines (Riazi et al., 2008; Henry et al., 2009).”
BackgroundImpact of consuming a milk drink containing a probiotic on mood and cognition
Benton, D., Williams, C., & Brown, A. (2007) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602546 · Cited by 554
Qin, L., He, J., Hanes, R. N., Pluzarev, O., Hong, J.-S., & Crews, F. T. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-10 · Cited by 532
Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis
Benveniste, E. N. (1997) · Journal of Molecular Medicine · doi:10.1007/s001090050101 · Cited by 532 · cited 1×
“Yacyshyn et al., 1996; Benveniste, 1997; Heppner et al., 2005; Sun et al., 2006; Piccio et al., 2007; Yokote et al., 2008; Frischer et al., 2009; Napoli and Neumann, 2010; Lee et al., 2011; Vogel et al., 2013; Miyake et al., 2015; Cekanaviciute et al., 2017; Gao et al., 2017; Kosmidou et al., 2017;…”
BackgroundGastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development
Chaidez, V., Hansen, R. L., & Hertz-Picciotto, I. (2014) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-013-1973-x · Cited by 528 · cited 2×
“In addition, symptoms of gut dysfunction such as irritable bowel syndrome, chronic diarrhea, and/or constipation are found in 23–70% of patients with ASD (Chaidez et al., 2014).”
BackgroundMost Tissue-Resident Macrophages Except Microglia Are Derived from Fetal Hematopoietic Stem Cells
Sheng, J., Ruedl, C., & Karjalainen, K. (2015) · Immunity · doi:10.1016/j.immuni.2015.07.016 · Cited by 523
Hamelin, L., Lagarde, J., Dorothée, G., Leroy, C., Labit, M., Comley, R. A., de Souza, L. C., Corne, H., Dauphinot, L., Bertoux, M., et al. (2016) · Brain · doi:10.1093/brain/aww017 · Cited by 519
Gupta, S., Ellis, S. E., Ashar, F. N., Moes, A., Bader, J. S., Zhan, J., West, A. B., & Arking, D. E. (2014) · Nature Communications · doi:10.1038/ncomms6748 · Cited by 504 · cited 1×
“Postmortem analysis of brain tissue collected from ASD patients show perturbations in microglial immune surveillance and synaptic remodeling, with evidence for heightened microglial activation, including increased expression of MHC II, elevated levels of pro- and anti-inflammatory cytokines, and increased microglial d…”
BackgroundAdult hippocampal neurogenesis is regulated by the microbiome
Ogbonnaya, E. S., Clarke, G., Shanahan, F., Dinan, T. G., Cryan, J. F., & O’Leary, O. F. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.12.023 · Cited by 491 · cited 1×
“, lacking all commensal and pathogenic microbes) mice, antibiotics, fecal microbiota transplant (FMT), and pre-/probiotics have demonstrated a role for gut bacteria in neurotransmitter signaling, synaptic plasticity, myelination, and neurogenesis (Diaz Heijtz et al., 2011; Neufeld et al., 2011; Ogbonnaya et al., 2015;…”
BackgroundThe Enteric Network: Interactions between the Immune and Nervous Systems of the Gut
Yoo, B. B., & Mazmanian, S. K. (2017) · Immunity · doi:10.1016/j.immuni.2017.05.011 · Cited by 485 · cited 1×
“Communication between gut microbes and the CNS is mediated by a combination of immune, enteric, and neural pathways that provide physical and chemical connections between the CNS and the periphery, and several experimental paradigms have been used to demonstrate that gut microbes influence many facets of CNS physiolog…”
BackgroundSelf-citationMacrophages in inflammatory multiple sclerosis lesions have an intermediate activation status
Vogel, D. Y., Vereyken, E. J., Glim, J. E., Heijnen, P. D., Moeton, M., van der Valk, P., Amor, S., Teunissen, C. E., van Horssen, J., & Dijkstra, C. D. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-35 · Cited by 479
Synuclein activates microglia in a model of Parkinson's disease
Su, X., Maguire-Zeiss, K. A., Giuliano, R., Prifti, L., Venkatesh, K., & Federoff, H. J. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.04.006 · Cited by 474
Sun, S., Liang, H., Trinkaus, K., Cross, A. H., Armstrong, R. C., & Song, S. (2006) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20774 · Cited by 461
Vagotomy and Parkinson disease: A Swedish register–based matched-cohort study
Liu, B., Fang, F., Pedersen, N. L., Tillander, A., Ludvigsson, J. F., Ekbom, A., Svenningsson, P., Chen, H., & Wirdefeldt, K. (2017) · Neurology · doi:10.1212/wnl.0000000000003961 · Cited by 447
Bloomfield, P. S., Selvaraj, S., Veronese, M., Rizzo, G., Bertoldo, A., Owen, D. R., Bloomfield, M., Bonoldi, I., Kalk, N. J., Turkheimer, F., et al. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.14101358 · Cited by 446
Goehler, L. E., Gaykema, R. P. A., Opitz, N., Reddaway, R., Badr, N., & Lyte, M. (2005) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2004.09.002 · Cited by 442 · cited 3×
“Communication through the vagus nerve is essential for signals mediating satiety, stress, and mood, and these signals are governed by changes in enteric neuron activity and the behavior of gut microbes (Goehler et al., 2005; Forsythe et al., 2014; Browning et al., 2017).”
BackgroundThe role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia
Na, K., Jung, H., & Kim, Y. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.10.022 · Cited by 434
Melancholic microbes: a link between gut microbiota and depression
Dinan, T. G., & Cryan, J. F. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12198 · Cited by 424
Wang, L., Christophersen, C. T., Sorich, M. J., Gerber, J. P., Angley, M. T., & Conlon, M. A. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-42 · Cited by 418
Norden, D. M., Muccigrosso, M. M., & Godbout, J. P. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.10.028 · Cited by 413 · cited 1×
“In each case, there is evidence of immune activation, suggesting a role for microglia-driven inflammation as an etiologic factor (Perry and Holmes, 2014; Norden et al., 2015).”
BackgroundWang, L., Christophersen, C. T., Sorich, M. J., Gerber, J. P., Angley, M. T., & Conlon, M. A. (2012) · Digestive Diseases and Sciences · doi:10.1007/s10620-012-2167-7 · Cited by 412
Gastrointestinal microbiology enters the metagenomics era
Frank, D. N., & Pace, N. R. (2008) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e3282f2b0e8 · Cited by 410 · cited 1×
“Within this complex community in humans are >1,000 bacterial species (Frank and Pace, 2008).”
Background(Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease
Buford, T. W. (2017) · Microbiome · doi:10.1186/s40168-017-0296-0 · Cited by 409 · cited 2×
“Similar to neurodevelopmental disorders, this trend suggests that microbiota-driven changes in microglial behavior might have a larger role in the onset or progression of neurodegenerative disorders than previously thought (Buford, 2017).”
BackgroundRiazi, K., Galic, M. A., Kuzmiski, J. B., Ho, W., Sharkey, K. A., & Pittman, Q. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806682105 · Cited by 400 · cited 2×
“Indeed, increased intestinal inflammation driven by either LPS or bacterial infection correlates with elevated levels of microglial activation and release of pro-inflammatory cytokines (Riazi et al., 2008; Henry et al., 2009).”
BackgroundExploring Braak’s hypothesis of Parkinson’s disease
Rietdijk, C. D., Perez-Pardo, P., Garssen, J., van Wezel, R. J. A., & Kraneveld, A. D. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00037 · Cited by 395
Komatsuzaki, N., Shima, J., Kawamoto, S., Momose, H., & Kimura, T. (2005) · Food Microbiology · doi:10.1016/j.fm.2005.01.002 · Cited by 391 · cited 1×
“Circulation of microbe-derived neurotransmitters, including acetylcholine (Lactobacillus), GABA (Bifidobacteria and Lactobacillus), and serotonin (Enterococcus and Streptococcus), can potentially influence microglial activation through direct and indirect means (Komatsuzaki et al., 2005; Yano et al., 2015; Pokusaeva e…”
BackgroundHo, L., Ono, K., Tsuji, M., Mazzola, P., Singh, R., & Pasinetti, G. M. (2018) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2018.1400909 · Cited by 376
Microbiota alteration is associated with the development of stress-induced despair behavior
Marin, I. A., Goertz, J. E., Ren, T., Rich, S. S., Onengut-Gumuscu, S., Farber, E., Wu, M., Overall, C. C., Kipnis, J., & Gaultier, A. (2017) · Scientific Reports · doi:10.1038/srep43859 · Cited by 369
Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies
van Kesteren, C. F. M. G., Gremmels, H., de Witte, L. D., Hol, E. M., Gool, A. R. V., Falkai, P., Kahn, R. S., & Sommer, I. E. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.4 · Cited by 368
The vagus nerve in appetite regulation, mood, and intestinal inflammation
Browning, K. N., Verheijden, S., & Boeckxstaens, G. E. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.10.046 · Cited by 361
Goehler, L. E., Gaykema, R. P. A., Nguyen, K. T., Lee, J. E., Tilders, F. J. H., Maier, S. F., & Watkins, L. R. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02799.1999 · Cited by 357 · cited 1×
“Upon sensing a change in inflammation, such as increased production of pro-inflammatory cytokines, vagal afferents relay this information to the CNS and can ultimately influence the level of neuroinflammation (Goehler et al., 1999).”
BackgroundThe role of small intestinal bacterial overgrowth in Parkinson's disease
Fasano, A., Bove, F., Gabrielli, M., Petracca, M., Zocco, M. A., Ragazzoni, E., Barbaro, F., Piano, C., Fortuna, S., Tortora, A., et al. (2013) · Movement Disorders · doi:10.1002/mds.25522 · Cited by 344
GABA ‐producing Bifidobacterium dentium modulates visceral sensitivity in the intestine
Pokusaeva, K., Johnson, C., Luk, B., Uribe, G., Fu, Y., Oezguen, N., Matsunami, R. K., Lugo, M., Major, A., Mori‐Akiyama, Y., et al. (2017) · Neurogastroenterology & Motility · doi:10.1111/nmo.12904 · Cited by 337 · cited 1×
“Circulation of microbe-derived neurotransmitters, including acetylcholine (Lactobacillus), GABA (Bifidobacteria and Lactobacillus), and serotonin (Enterococcus and Streptococcus), can potentially influence microglial activation through direct and indirect means (Komatsuzaki et al., 2005; Yano et al., 2015; Pokusaeva e…”
BackgroundMorphometric characterization of microglial phenotypes in human cerebral cortex
Torres-Platas, S. G., Comeau, S., Rachalski, A., Bo, G. D., Cruceanu, C., Turecki, G., Giros, B., & Mechawar, N. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-12 · Cited by 329 · cited 2×
“Under steady-state conditions, surveying microglia have a ramified morphology with a small cell body and many long extended processes that are used to continuously scan and assess the health of cells in close proximity—a process critical for maintaining homeostasis in the absence of pathology (Nimmerjahn et al., 2005;…”
BackgroundNeuroinflammation in schizophrenia especially focused on the role of microglia
Monji, A., Kato, T. A., Mizoguchi, Y., Horikawa, H., Seki, Y., Kasai, M., Yamauchi, Y., Yamada, S., & Kanba, S. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.12.002 · Cited by 314
Immune-mediated Mechanisms in the Pathoprogression of Amyotrophic Lateral Sclerosis
Zhao, W., Beers, D. R., & Appel, S. H. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9489-x · Cited by 309
Short-Chain Fatty Acids Suppress Cholesterol Synthesis in Rat Liver and Intestine
Hara, H., Haga, S., Aoyama, Y., & Kiriyama, S. (1999) · Journal of Nutrition · doi:10.1093/jn/129.5.942 · Cited by 307
Microglial Dysregulation in Psychiatric Disease
Frick, L. R., Williams, K., & Pittenger, C. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/608654 · Cited by 299 · cited 1×
“In addition to their innate immune and homeostatic functions, microglia have been implicated in the pathogenesis of a broad spectrum of neurodegenerative and behavioral diseases, including PD, Alzheimer’s disease (AD), multiple sclerosis (MS), schizophrenia, and ASD (Vargas et al., 2005; Hirsch et al., 2012; Frick et…”
BackgroundAllergy and the gastrointestinal system
Vighi, G., Marcucci, F., Sensi, L., Di Cara, G., & Frati, F. (2008) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2008.03713.x · Cited by 291 · cited 1×
“Approximately 70–80% of immune cells in the human body are found in the gut, allowing for direct gut–immune cell interactions (Vighi et al., 2008).”
BackgroundNonmotor symptoms as presenting complaints in Parkinson’s disease: a clinicopathological study
O'Sullivan, S. S., Williams, D. R., Gallagher, D. A., Massey, L. A., Silveira‐Moriyama, L., & Lees, A. J. (2008) · Movement Disorders · doi:10.1002/mds.21813 · Cited by 290
Extracellular mutant SOD1 induces microglial‐mediated motoneuron injury
Zhao, W., Beers, D. R., Henkel, J. S., Zhang, W., Urushitani, M., Julien, J., & Appel, S. H. (2010) · Glia · doi:10.1002/glia.20919 · Cited by 288
Target intestinal microbiota to alleviate disease progression in amyotrophic lateral sclerosis
Zhang, Y.-G., Wu, S., Yi, J., Xia, Y., Jin, D., Zhou, J., & Sun, J. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2016.12.014 · Cited by 287
Blockade of TREM‐2 exacerbates experimental autoimmune encephalomyelitis
Piccio, L., Buonsanti, C., Mariani, M., Cella, M., Gilfillan, S., Cross, A. H., Colonna, M., & Panina‐Bordignon, P. (2007) · European Journal of Immunology · doi:10.1002/eji.200636837 · Cited by 284
The Microbiota and Microbiome in Aging: Potential Implications in Health and Age‐Related Diseases
Zapata, H. J., & Quagliarello, V. J. (2015) · Journal of the American Geriatrics Society · doi:10.1111/jgs.13310 · Cited by 279
Small intestinal bacterial overgrowth in Parkinson's disease
Tan, A. H., Mahadeva, S., Thalha, A. M., Gibson, P. R., Kiew, C. K., Yeat, C. M., Ng, S. W., Ang, S. P., Chow, S. K., Tan, C. T., et al. (2014) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2014.02.019 · Cited by 274
Castro‐Nallar, E., Bendall, M. L., Pérez‐Losada, M., Sabunciyan, S., Severance, E. G., Dickerson, F., Schroeder, J. R., Yolken, R. H., & Crandall, K. A. (2015) · PeerJ · doi:10.7717/peerj.1140 · Cited by 272
NKT Cell-Dependent Amelioration of a Mouse Model of Multiple Sclerosis by Altering Gut Flora
Yokote, H., Miyake, S., Croxford, J. L., Oki, S., Mizusawa, H., & Yamamura, T. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080622 · Cited by 271
Leaky intestine and impaired microbiome in an amyotrophic lateral sclerosis mouse model
Wu, S., Yi, J., Zhang, Y.-G., Zhou, J., & Sun, J. (2015) · Physiological Reports · doi:10.14814/phy2.12356 · Cited by 267
Sierra, A., de Castro, F., del Río‐Hortega, J., Rafael Iglesias‐Rozas, J., Garrosa, M., & Kettenmann, H. (2016) · Glia · doi:10.1002/glia.23046 · Cited by 266 · cited 1×
“20180794 42 Microglia during development and adulthood Microglia maturation Microglia were first discovered in the early 20th century by Pío del Río-Hortega, who pioneered exploration of microglial morphology and function (Sierra et al., 2016).”
BackgroundMacFabe, D. F. (2015) · Microbial Ecology in Health and Disease · doi:10.3402/mehd.v26.28177 · Cited by 263 · cited 1×
“SCFAs have been shown to activate sympathetic nervous system activity and alleviate intestinal inflammation, and altered SCFA production has been demonstrated in a variety of neuropathologies such as PD and ASD (Smith et al., 2013; MacFabe, 2015; Unger et al., 2016).”
BackgroundChen, P. S., Wang, C.-C., Bortner, C. D., Peng, G.-S., Wu, X., Pang, H., Lu, R.-B., Gean, P.-W., Chuang, D.-M., & Hong, J.-S. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.06.053 · Cited by 262 · cited 1×
“Indeed, treatment of microglial cells in vitro with various SCFAs, including valproic acid and butyric acid, elevates levels of acetylation of histone H3 (Chen et al., 2007).”
BackgroundRochfort, K. D., Collins, L. E., Murphy, R. P., & Cummins, P. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101815 · Cited by 261
Martínez‐Cerdeño, V. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22417 · Cited by 256 · cited 2×
“…et al., 2013; Hsiao et al., 2013; Kang et al., 2013; Wang et al., 2013; De Rubeis et al., 2014; Gupta et al., 2014; Hsiao, 2014; Zhan et al., 2014; Koyama and Ikegaya, 2015; Martínez-Cerdeño, 2017 Synaptic and neural circuitry dysfunction found in postmortem brain tissue from individuals with ASD.”
BackgroundThe Dual Role of Microglia in ALS: Mechanisms and Therapeutic Approaches
Geloso, M. C., Corvino, V., Marchese, E., Serrano, A., Michetti, F., & D’Ambrosi, N. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00242 · Cited by 254
Watson, M. B., Richter, F., Lee, S., Gabby, L. C., Wu, J. E., Masliah, E., Effros, R. B., & Chesselet, M. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.06.025 · Cited by 254
Gut chemosensing: Interactions between gut endocrine cells and visceral afferents
Raybould, H. E. (2010) · Autonomic Neuroscience · doi:10.1016/j.autneu.2009.07.007 · Cited by 254 · cited 1×
“Additionally, metabolites and neuroactive substances produced by microbes activate chemoreceptors located at vagal nerve endings (Hara et al., 1999; Raybould, 2010).”
BackgroundGomes, C. A., Ferreira, R., George, J., Sanches, R., Rodrigues, D. I., Gonçalves, N., & Cunha, R. A. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-16 · Cited by 244 · cited 1×
“In addition to dictating neuronal density, microglia supply a steady stream of neurotrophic factors (such as nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], and insulin-like growth factor 1 [IGF-1]) that promote neuronal survival and differentiation of neural progenitors (Gomes et al., 2013; Ueno…”
BackgroundReisinger, S. N., Khan, D., Kong, E., Berger, A., Pollak, A. J., & Pollak, D. D. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.01.001 · Cited by 238
Microglia function during brain development: New insights from animal models
Bilimoria, P. M., & Stevens, B. (2015) · Brain Research · doi:10.1016/j.brainres.2014.11.032 · Cited by 237 · cited 1×
“In addition to their innate immune and homeostatic functions, microglia have been implicated in the pathogenesis of a broad spectrum of neurodegenerative and behavioral diseases, including PD, Alzheimer’s disease (AD), multiple sclerosis (MS), schizophrenia, and ASD (Vargas et al., 2005; Hirsch et al., 2012; Frick et…”
BackgroundGut inflammation and dysbiosis in human motor neuron disease
Rowin, J., Xia, Y., Jung, B., & Sun, J. (2017) · Physiological Reports · doi:10.14814/phy2.13443 · Cited by 224
Mattei, D., Ivanov, A., Ferrai, C., Jordan, P., Guneykaya, D., Buonfiglioli, A., Schaafsma, W., Przanowski, P., Deuther-Conrad, W., Brust, P., et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.80 · Cited by 222 · cited 8×
“Adult MIA offspring exhibit heightened microglial activation, as noted by increased levels of IL-6 and TNF-α (Pratt et al., 2013; Mattei et al., 2017).”
BackgroundInfluentialSerotonin stimulates secretion of exosomes from microglia cells
Glebov, K., Löchner, M., Jabs, R., Lau, T., Merkel, O., Schloss, P., Steinhäuser, C., & Walter, J. (2015) · Glia · doi:10.1002/glia.22772 · Cited by 221 · cited 1×
“Binding of serotonin to 5-HT receptors on microglia induces release of cytokine-carrying exosomes, providing another mechanism for gut-induced modulation of neuroinflammation (Glebov et al., 2015).”
BackgroundThe “psychomicrobiotic”: targeting microbiota in major psychiatric disorders: a systematic review
Fond, G., Boukouaci, W., Chevalier, G., Regnault, A., Eberl, G., Hamdani, N., Dickerson, F., Macgregor, A., Boyer, L., Dargel, A., et al. (2015) · Pathologie Biologie · doi:10.1016/j.patbio.2014.10.003 · Cited by 219
Gastrointestinal issues in autism spectrum disorder
Hsiao, E. Y. (2014) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000029 · Cited by 209 · cited 1×
“De Angelis et al., 2013; Hsiao et al., 2013; Kang et al., 2013; Wang et al., 2013; De Rubeis et al., 2014; Gupta et al., 2014; Hsiao, 2014; Zhan et al., 2014; Koyama and Ikegaya, 2015; Martínez-Cerdeño, 2017 Synaptic and neural circuitry dysfunction found in postmortem brain tissue from individuals…”
BackgroundGastroenterology Issues in Schizophrenia: Why the Gut Matters
Severance, E. G., Prandovszky, E., Castiglione, J., & Yolken, R. H. (2015) · Current Psychiatry Reports · doi:10.1007/s11920-015-0574-0 · Cited by 198
The role of microglia in multiple sclerosis
Luo, C., Jian, C., Liao, Y., Huang, Q., Wu, Y., Liu, X., Zou, D., & Wu, Y. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s140634 · Cited by 187
Protective effects of microglia in multiple sclerosis
Napoli, I., & Neumann, H. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.04.024 · Cited by 173
Microglial response to 6-hydroxydopamine-induced substantia nigra lesions
Akiyama, H., & McGeer, P. L. (1989) · Brain Research · doi:10.1016/0006-8993(89)90857-3 · Cited by 169
Shaw, W. (2010) · Nutritional Neuroscience · doi:10.1179/147683010x12611460763968 · Cited by 162 · cited 1×
“West et al., 2006; Severance et al., 2010, 2015; Shaw, 2010; Diaz Heijtz et al., 2011; Miller et al., 2011; Monji et al., 2013; Hercher et al., 2014; Na et al., 2014; Yolken and Dickerson, 2014; Castro-Nallar et al., 2015; Reisinger et al., 2015; Bloomfield et al., 2016; Sekar et al., 2016; van…”
BackgroundStarke Belege: Parkinson könnte im Verdauungstrakt beginnen
(2017) · Fortschritte der Neurologie · Psychiatrie · doi:10.1055/s-0043-113319 · Cited by 160 · cited 1×
“While this pattern of α-synuclein spreading is not observed in all cases of sporadic PD, vagotomy may be associated with reduced risk of developing PD in humans, potentially implicating peripheral influences on disease development (Svensson et al., 2015; Liu et al., 2017).”
BackgroundTanida, M., Yamano, T., Maeda, K., Okumura, N., Fukushima, Y., & Nagai, K. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.07.036 · Cited by 159 · cited 1×
“Oral inoculation with the pathogen Campylobacter jejuni or intraduodenal injection of the probiotic strain Lactobacillus johnsonii are sufficient to induce activation of vagal sensory neurons innervating the GI tract, as well as neurons in the brainstem (Goehler et al., 2005; Tanida et al., 2005).”
BackgroundHercher, C., Chopra, V. S., & Beasley, C. L. (2014) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.130277 · Cited by 157
Mertsalmi, T. H., Aho, V. T. E., Pereira, P. A. B., Paulin, L., Pekkonen, E., Auvinen, P., & Scheperjans, F. (2017) · European Journal of Neurology · doi:10.1111/ene.13398 · Cited by 153
Koenigsknecht-Talboo, J., Meyer-Luehmann, M., Parsadanian, M., Garcia-Alloza, M., Finn, M. B., Hyman, B. T., Bacskai, B. J., & Holtzman, D. M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4147-08.2008 · Cited by 149
Wang, X. (2002) · World Journal of Gastroenterology · doi:10.3748/wjg.v8.i3.540 · Cited by 143 · cited 1×
“Indeed, the anxiolytic effects of administration of the probiotic species Lactobacillus rhamnosus and Bifidobacterium longum is absent in vagotomized mice, providing strong evidence that gut–vagal nerve interactions regulate social behavior (Wang et al., 2002; Bercik et al., 2011; Bravo et al., 2011).”
BackgroundMicroglia in the pathogenesis of autism spectrum disorders
Koyama, R., & Ikegaya, Y. (2015) · Neuroscience Research · doi:10.1016/j.neures.2015.06.005 · Cited by 141
Gao, H., Danzi, M. C., Choi, C. S., Taherian, M., Hansen, C. D., Ellman, D. G., Madsen, P. M., Bixby, J. L., Lemmon, V., Lambertsen, K. L., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.11.083 · Cited by 140
Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments
Poirier, A.-A., Aubé, B., Côté, M., Morin, N., Di Paolo, T., & Soulet, D. (2016) · Parkinson s Disease · doi:10.1155/2016/6762528 · Cited by 130
Microbial metabolites in health and disease: Navigating the unknown in search of function
Martinez, K., Leone, V., & Chang, E. B. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.752899 · Cited by 130 · cited 1×
“The diverse repertoire of metabolites and signaling molecules produced by gut bacteria enter the systemic circulation, facilitating the molecular crosstalk between host and microbes throughout the body (Martinez et al., 2017).”
BackgroundKaczmarczyk, R., Tejera, D., Simon, B. J., & Heneka, M. T. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14284 · Cited by 118 · cited 1×
“Electrical stimulation of the vagus nerve in the presence of an immune challenge in the periphery has downstream effects on microglial behavior, including up-regulation of anti-inflammatory pathways in the brain (Frasch et al., 2016; Meneses et al., 2016; Kaczmarczyk et al., 2017).”
BackgroundYacyshyn, B., Meddings, J. B., Sadowski, D. C., & Bowen-Yacyshyn, M. B. (1996) · Digestive Diseases and Sciences · doi:10.1007/bf02100148 · Cited by 116
Multiple sclerosis and inflammatory bowel diseases: a systematic review and meta-analysis
Kosmidou, M. S., Katsanos, A. H., Katsanos, K. H., Kyritsis, A. P., Tsivgoulis, G. K., Christodoulou, D. K., & Giannopoulos, S. (2016) · Journal of Neurology · doi:10.1007/s00415-016-8340-8 · Cited by 115
Meneses, G., Bautista, M., Florentino, A., Díaz, G., Acero, G., Besedovsky, H., Meneses, D., Fleury, A., Del Rey, A., Gevorkian, G., et al. (2016) · Journal of Inflammation · doi:10.1186/s12950-016-0140-5 · Cited by 112 · cited 2×
“Vagus nerve stimulation combined with LPS challenge has also been reported to decrease microglial production of the pro-inflammatory cytokines IL-6, IL-1β, and TNFα in the brain, an effect no longer observed following vagotomy (Meneses et al., 2016).”
BackgroundThe Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke
Winek, K., Dirnagl, U., & Meisel, A. (2016) · Neurotherapeutics · doi:10.1007/s13311-016-0475-x · Cited by 108
Xiang, Z., Haroutunian, V., Ho, L., Purohit, D., & Pasinetti, G. M. (2006) · Disease Markers · doi:10.1155/2006/276239 · Cited by 101
Developmental microglial priming in postmortem autism spectrum disorder temporal cortex
Lee, A. S., Azmitia, E. C., & Whitaker‐Azmitia, P. M. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.01.019 · Cited by 100 · cited 1×
“Postmortem analysis of brain tissue collected from ASD patients show perturbations in microglial immune surveillance and synaptic remodeling, with evidence for heightened microglial activation, including increased expression of MHC II, elevated levels of pro- and anti-inflammatory cytokines, and increased microglial d…”
BackgroundThe microbiota influences cell death and microglial colonization in the perinatal mouse brain
Castillo-Ruiz, A., Mosley, M., George, A. J., Mussaji, L. F., Fullerton, E. F., Ruszkowski, E. M., Jacobs, A. J., Gewirtz, A. T., Chassaing, B., & Forger, N. G. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.08.027 · Cited by 91 · cited 1×
“Altered microglial morphology and density, as well as attenuated inflammatory responses, are also observed in offspring of GF dams immediately after birth, a time when microglia typically exhibit an activated phenotype (Castillo-Ruiz et al., 2018).”
BackgroundFine-tuning the central nervous system: microglial modelling of cells and synapses
Xavier, A. L. R., Menezes, J. R. L., Goldman, S. A., & Nedergaard, M. (2014) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0593 · Cited by 80 · cited 1×
“Within the CNS, microglial activity is governed in part by cytokines and chemokines, neurotransmitters, and other molecules that regulate signaling pathways that influence various brain functions (Xavier et al., 2014).”
BackgroundPratt, L., Ni, L., Ponzio, N. M., & Jonakait, G. M. (2013) · Pediatric Research · doi:10.1038/pr.2013.126 · Cited by 77 · cited 8×
“Adult MIA offspring exhibit heightened microglial activation, as noted by increased levels of IL-6 and TNF-α (Pratt et al., 2013; Mattei et al., 2017).”
BackgroundInfluentialMachado, V., Zöller, T., Attaai, A., & Spittau, B. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020151 · Cited by 76
Gerber, Y. N., Sabourin, J.-C., Rábano, M., Vivanco, M. D., & Perrin, F. E. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036000 · Cited by 76
Characterization of alpha-keto acid transport across blood-brain barrier in rats
Conn, A. R., Fell, D. I., & Steele, R. D. (1983) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1983.245.3.e253 · Cited by 65 · cited 6×
“Increased circulation of BBB-permeable pro-inflammatory cytokines and neurotoxic compounds may contribute to heightened microglial activation and production of pro-inflammatory cytokines in the brain (Qin et al., 2008; Riazi et al., 2008).”
BackgroundInfluentialNeedham, B. D., Tang, W., & Wu, W. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22581 · Cited by 60 · cited 1×
“Other preclinical models have provided insight into the role of the microbiota and microglia in driving the pathology of ASD (Needham et al., 2018).”
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
“As alluded to in earlier sections, microbiota-microglia interactions are receiving much attention of late as key mechanisms underlying microbiota-immune-brain interactions (3, 1243, 1576).”
BackgroundInteraction between microbiota and immunity in health and disease
Zheng, D., Liwinski, T., & Elinav, E. (2020) · Cell Research · doi:10.1038/s41422-020-0332-7 · Cited by 3,947
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204
“physiology are regulated by the microbiome, including microglial maturation and function (Abdel-Haq et al., 2019).”
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043
“These neurotransmitters can potentially influence microglial activation and several cerebral functions (54).”
BackgroundThe gut microbiota–brain axis in behaviour and brain disorders
Morais, L. H., Schreiber, H. L., & Mazmanian, S. K. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-00460-0 · Cited by 2,149
Self-citation
Metadata
- Authors
- Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., & Mazmanian, S. K.
- Affiliations
- California Institute of Technology (US)
- University of California San Diego (US)
- Corresponding author
- Abdel-Haq, Reem
- Mazmanian, Sarkis K.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2018-11-01
- Volume
- 216
- Issue
- 1
- Pages
- 41-59
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC6314531
- OpenAlex
- W2899046125
- Cited by
- 471
- References
- 214
- Citations by year
- 2026: 51 · 2025: 78 · 2024: 70 · 2023: 76 · 2022: 77 · 2021: 46 · 2020: 38 · 2019: 33
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- U.S. Department of Defense (PD160030)
- Donna and Benjamin M. Rosen Bioengineering Center
- National Institutes of Health (AG057706, NS096170, MH100556, NS085910)
- Heritage Medical Research Institute
- Simons Foundation (322839)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, microglia, gut-brain axis, neuroinflammation, microglial maturation, neurodevelopmental disorders, neurodegenerative diseases, microbial treatment, brain microenvironment
- MeSH terms
- Gastrointestinal Microbiome, Animals, Brain, Humans, Intestines, Microglia, Neurodegenerative Diseases, Neurodevelopmental Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
