The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options

May combine two claims.

Intermittent fasting can protect neurons in animal models of disease, reduce the number of dopaminergic neurons and improve motor function in Parkinson's disease.

“Intermittent fasting can protect neurons in animal models of disease, reduce the number of dopaminergic neurons and improve motor function in Parkinson's disease.250”

• cites [250] Mattson, 2017, Impact of intermittent fasting on health and disease processes, Ageing Res Rev sourceDisputed

  Section 2.1 reports that mice on alternate-day fasting had reduced loss of dopaminergic neurons and improved functional outcomes in a Parkinson’s disease model. This supports the neuroprotection and functional-outcome portions of the claim, but contradicts its statement that fasting reduces the number of dopaminergic neurons. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Some studies suggested that there was no significant difference in the amount of microbiota in the nasal cavity of patients with Parkinson's disease, but the nasal microbiota exhibited a higher variability in different individuals.

“Some studies suggested that there was no significant difference in the amount of microbiota in the nasal cavity of patients with Parkinson's disease, but the nasal microbiota exhibited a higher variability in different individuals.34”

• cites [34] Heintz-Buschart, 2018, The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behaviour disorder, Mov Disord sourcePartly supported

  The Discussion reports that nasal microbiota varied more across individuals and that few bacterial families differed between Parkinson’s patients and healthy controls. The Results nevertheless identify eight differentially abundant nasal families, mostly with weak significance. The paper does not establish that the total amount of nasal microbiota was the same in the two groups. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Akkermansia muciniphila may improve insulin resistance of Alzheimer's disease mice, reduce the decrease in colonic mucous cells, improve intestinal barrier dysfunction and dyslipidaemia, and delay pathological changes in the brain.

“Recently, Ou et al. 47 suggested that A. muciniphila may improve the insulin resistance of Alzheimer's disease mice, reduce the decrease in colonic mucous cells, improve intestinal barrier dysfunction and dyslipidaemia, and delay pathological changes in the brain”

• cites [47] Ou, 2020, Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer's disease, Nutr Diabetes sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Microbial intervention could provide a novel strategy for the prevention and treatment of Alzheimer's disease.

“therefore, microbial intervention could provide a novel strategy for the prevention and treatment of Alzheimer's disease.47”

• cites [47] Ou, 2020, Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer's disease, Nutr Diabetes sourceSupported

May combine two claims.

Early antibiotic treatment changed intestinal microbiota significantly and altered short-chain fatty acid metabolism.

“In addition, by investigating the effect of early antibiotics on intestinal microbiota, a study revealed that the composition of intestinal microbiota changed significantly and the metabolism of SCFAs was altered after treatment with subtherapeutic antibiotic therapy.56”

• cites [56] Cho, 2012, Antibiotics in early life alter the murine colonic microbiome and adiposity, Nature sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

More than 80% of patients with Parkinson's disease experience severe gastrointestinal symptoms such as constipation, nausea and vomiting.

“More than 80% of patients with Parkinson's disease experience a variety of severe gastrointestinal symptoms such as constipation, nausea and vomiting.9”

• cites [9] Yang, 2019, The role of the gut microbiota in the pathogenesis of Parkinson's disease, Front Neurol sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Ciprofloxacin treatment causes a decrease in bacterial diversity and a significant change in microbiota composition within a 3-4-day treatment, after which it began to return incompletely to the initial state.

“For example, Dethlefsen and Relman 53 examined the effect of ciprofloxacin on human distal intestinal microbiota and found a decrease in bacterial diversity and a significant change in microbiota composition within a 3-4-day treatment, after which it began to return incompletely to the initial state.53”

• cites [53] Dethlefsen, 2011, Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation, Proc Natl Acad Sci U S A sourcePartly supported

  The Abstract and Results report a rapid loss of diversity and shift in composition within 3–4 days of starting ciprofloxacin, followed by an often-incomplete return toward the initial state. But the Results specify two 5-day treatment courses, and the Abstract says communities began to return by one week after each course ended—not immediately after a 3–4-day treatment. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Akkermansia utilize mucin as a source of energy and may therefore reduce barrier function and increase exposure to more microbial substrates across the epithelial lining.

“Akkermansia utilize mucin as a source of energy and may therefore reduce barrier function and increase exposure to more microbial substrates across the epithelial lining.44”

• cites [44] Gerhardt, 2018, Changes of colonic bacterial composition in Parkinson's disease and other neurodegenerative diseases, Nutrients sourcePartly supported

  The Discussion says Akkermansia uses mucus for energy and degrades the mucus layer, which could increase microbial-antigen exposure to immune cells. It does not say that microbial substrates cross the epithelial lining, and it also reports that A. muciniphila improves epithelial barrier function. The proposed reduction in barrier function is therefore not established by this passage. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

In mice colonized by the faeces of patients with Parkinson's disease, the abundance of Proteus sp., Bilophila sp. and Roseburia sp. increased, with a decrease in Lachnospiracae, Rikenellae, Peptostreptococacae and Butyricicoccus sp.

“Intriguingly, the abundance of some gut microbiota increased in mice that were colonized by the faeces of patients with Parkinson's disease, including Proteus sp., Bilophila sp. and Roseburia sp., with a decrease in the Lachnospiracae, Rikenellae, Peptostreptococacae and Butyricicoccus sp.50”

• cites [50] Sampson, 2016, Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease, Cell sourceSupported

May combine two claims.

The gut microbiota is significantly related to the duration, onset time, and motor and non-motor symptoms of Parkinson's disease.

“Investigators have shown that the gut microbiota is significantly related to the duration, 28,35 onset time, 35 and motor and non-motor symptoms 23,25,29,34,40 of Parkinson's disease.”

• cites [28] Keshavarzian, 2015, Colonic bacterial composition in Parkinson's disease, Mov Disord sourceNot checked — no full text of the source
• cites [35] Lin, 2018, Gut microbiota in patients with Parkinson's disease in southern China, Parkinsonism Relat Disord sourceNot checked — no full text of the source
• cites [23] Barichella, 2019, Unraveling gut microbiota in Parkinson's disease and atypical parkinsonism, Mov Disord sourceNot checked — no full text of the source
• cites [25] Qian, 2018, Alteration of the faecal microbiota in Chinese patients with Parkinson's disease, Brain Behav Immun sourceNot checked — no full text of the source
• cites [29] Scheperjans, 2015, Gut microbiota are related to Parkinson's disease and clinical phenotype, Mov Disord sourceNot checked — no full text of the source
• cites [34] Heintz-Buschart, 2018, The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behaviour disorder, Mov Disord sourceSupported
• cites [40] Lin, 2019, Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease, J Neuroinflamm sourcePartly supported

  The Abstract and Discussion report that Bacteroides abundance correlated significantly with motor symptom severity. The paper assesses non-motor symptoms, but the passages found do not establish a microbiota association with them; searches for disease duration and age at onset likewise found no such association. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The enteric nervous system is made up of different neural networks in the intestinal wall, where individual small ganglia are connected by dense bundles of fibres.

“Unlike the CNS, the enteric nervous system is made up of different neural networks in the intestinal wall, where individual small ganglia are connected by dense bundles of fibres.70”

• cites [70] Endres, 2018, Influence of commensal microbiota on the enteric nervous system and its role in neurodegenerative diseases, J Innate Immun sourceSupported

May combine two claims.

In an alpha-synuclein transgenic mouse model, infiltration of CD3+/CD4+ helper T cells was increased in the brain in close proximity to astrocytes and microglia, accompanied by glial activation and enhanced expression of tumour necrosis factor genes.

“In an a-synuclein transgenic mouse model, infiltration of CD3 + /CD4 + helper T (Th) cells was increased in the brain (in close proximity to astrocytes and microglia) and this was accompanied by glial activation and enhanced expression of tumour necrosis factor (TNF) genes.88”

• cites [88] Iba, 2020, Neuroinflammation is associated with infiltration of T cells in Lewy body disease and alpha-synuclein transgenic models, J Neuroinflamm sourceSupported

May combine two claims.

T cell deficiency can decrease the loss of dopamine neurons and microglial major histocompatibility complex II expression.

“Intriguingly, T cell deficiency can decrease the loss of dopamine neurons and microglial major histocompatibility complex II expression.90”

• cites [90] Subbarayan, 2020, T cell infiltration and upregulation of MHCII in microglia leads to accelerated neuronal loss in an alpha-synuclein rat model of Parkinson's disease, J Neuroinflamm sourceSupported

May combine two claims.

T cells can recognize certain alpha-synuclein antigenic epitopes, and this is largely mediated by CD4+ T cells and CD8+ T cells in patients with Parkinson's disease.

“T cells can recognize certain a-synuclein antigenic epitopes, and this is largely mediated by CD4 + T cells and CD8 + T cells in patients with Parkinson's disease.94”

• cites [94] Sulzer, 2017, T cells from patients with Parkinson’s disease recognize α-synuclein peptides, Nature sourcePartly supported

  The passage describing responses in nine Parkinson’s disease participants (section labeled Abstract) confirms that T cells recognized α-synuclein antigenic peptides. It says responses were largely mediated by CD4+ T cells, with potential CD8+ contributions; CD8+ cells mediated most of the response in only one participant. The claim overstates the CD8+ role by presenting both cell types as largely mediating the response. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

May combine two claims.

The autonomic nervous system receives afferent signals from the gastrointestinal tract and passes them along to the CNS through the spinal cord and vagus nerve pathway and also transmits signals from the CNS to the enteric nervous system.

“The autonomic nervous system receives afferent signals from the gastrointestinal tract and then passes them along to the CNS through the spinal cord and vagus nerve pathway and also transmits signals from the CNS to the enteric nervous system.66,67”

• cites [66] Gibbons, 2019, Basics of autonomic nervous system function, Handb Clin Neurol sourceNot checked — no full text of the source
• cites [67] Coletto, 2019, Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson's disease, NPJ Parkinsons Dis sourcePartly supported

  The Discussion (page unavailable) suggests that central dopaminergic changes may affect the dorsal motor nucleus of the vagus and vagal outflow, offering limited support for CNS-to-gut signaling. It does not describe gastrointestinal afferent signals traveling to the CNS through the spinal cord or vagus nerve, or explicitly trace signals from the CNS to the enteric nervous system. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

May combine two claims.

The level of autoantibodies to alpha-synuclein has been found to be significantly increased in CSF and associated with impaired cognition in patients with Parkinson's disease.

“The level of autoantibodies to asynuclein has been found to be significantly increased in CSF and associated with impaired cognition in patients with Parkinson's disease.96”

• cites [96] Akhtar, 2018, Measurements of auto-antibodies to alpha-synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease, J Neurochem sourceSupported

May combine two claims.

Increased expression of TLRs can increase the permeability of the intestinal epithelial barrier and increase the susceptibility of host colonic inflammation.

“The increased expression of TLRs can increase the permeability of the intestinal epithelial barrier and increase the susceptibility of host colonic inflammation, indicating that they play a crucial role in maintaining intestinal immune homeostasis.119,120”

• cites [119] Dheer, 2016, Intestinal epithelial Toll-Like receptor 4 signaling affects epithelial function and colonic microbiota and promotes a risk for transmissible colitis, Infect Immun sourcePartly supported

  The Results section ('TLR4 overexpression disrupts epithelial barrier function'; page unavailable) reports increased intestinal permeability in mice with enhanced epithelial TLR4 expression. The Introduction and Discussion also report greater susceptibility to colitis in these mice. The claim generalizes these findings from epithelial TLR4 in mice to TLRs broadly, which this paper does not establish. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [120] Terán-Ventura, 2014, Specific changes of gut commensal microbiota and TLRs during indomethacin-induced acute intestinal inflammation in rats, J Crohns Colitis sourcePartly supported

  Section 3.7 reports increased TLR-2 and TLR-4 expression in inflamed ileal and ceco-colonic tissue. The Discussion suggests this up-regulation might help aggravate or perpetuate inflammation, but it does not say that increased TLR expression raises epithelial barrier permeability or establish that it increases susceptibility to colonic inflammation. Page numbers were not available in our copy. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

In autoimmune conditions, peripheral inflammation caused by gut inflammation may trigger alpha-synuclein aggregation, increasing the permeability of the intestinal tract and blood-brain barrier and leading to neuroinflammation.

“In autoimmune conditions, peripheral inflammation caused by gut inflammation may trigger a-synuclein aggregation, increasing the permeability of intestinal tract and BBB and leading to neuroinflammation.98”

• cites [98] Brudek, 2019, Inflammatory bowel diseases and Parkinson's disease, J Parkinsons Dis sourceSupported

May combine two claims.

Roseburia can upregulate innate immune genes, including antimicrobial peptide genes, intestinal barrier function genes, and TLR-related genes such as TLR5 to enhance intestinal barrier function and reduce intestinal inflammation.

“Roseburia can upregulate innate immune genes, including antimicrobial peptide genes, intestinal barrier function genes, and TLR-related genes such as TLR5 to enhance intestinal barrier function and reduce intestinal inflammation.”

• cites [115] Patterson, 2017, Human gut symbiont roseburia hominis promotes and regulates innate immunity, Front Immunol sourceSupported

May combine two claims.

TLR4 gene knockout significantly alleviated the effects of rotenone on intestinal barrier destruction, reduced the expression of GFAP in the myenteric plexus and colonic alpha-synuclein aggregation, decreased microglial activation in the substantia nigra and the loss of dopaminergic cells and alleviated the impairment of motor function.

“Intriguingly, TLR4 gene knockout significantly alleviated the effects of rotenone on intestinal barrier destruction, reduced the expression of GFAP in the myenteric plexus and colonic a-synuclein aggregation, decreased microglial activation in the substantia nigra and the loss of dopaminergic cells and alleviated the impairment of motor function.120”

• cites [120] Terán-Ventura, 2014, Specific changes of gut commensal microbiota and TLRs during indomethacin-induced acute intestinal inflammation in rats, J Crohns Colitis sourceCould not verify

  Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Porphyromonas gingivalis-induced peripheral inflammation altered the gut microbiota, increased gut permeability and microglial activation and reduced dopaminergic neurons in the substantia nigra in a genetic mouse model of Parkinson's disease.

“Porphyromonas gingivalis-induced peripheral inflammation altered the gut microbiota, increased gut permeability and microglial activation and reduced dopaminergic neurons in the substantia nigra in a genetic mouse model of Parkinson's disease.100”

• cites [100] Feng, 2020, Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice, J Neuroinflamm sourcePartly supported

  The Abstract Results report fewer substantia nigra dopaminergic neurons and more activated microglia in R1441G mice given oral P. gingivalis; the Conclusions report impaired gut permeability. The Background says P. gingivalis can alter gut microbiota, but the paper does not report measuring a microbiota change in these mice. That part of the citing sentence is therefore not supported as a finding of this study. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Roseburia has a negative regulatory effect on the NF-kB pathway, promoting immune homeostasis by downregulating this inflammatory cascade.

“In addition, Roseburia has a negative regulatory effect on the NF-jB pathway, promoting immune homeostasis by downregulating this inflammatory cascade.115”

• cites [115] Patterson, 2017, Human gut symbiont roseburia hominis promotes and regulates innate immunity, Front Immunol sourcePartly supported

  The “R. hominis affects host innate signaling Pathways” section reports negative regulation of the NF-κB pathway by R. hominis. It says this *may* contribute to immune homeostasis, whereas the claim states that effect definitively and generalizes from R. hominis to Roseburia. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

In an Asian population, Bacteroides was associated with plasma TNF levels, while Verrucomicrobiaceae abundance was correlated with plasma interferon-gamma levels.

“Another study in Asian population observed that Bacteroides was associated with plasma TNF levels, while Verrucomicrobiaceae abundance was correlated with plasma IFNc levels”

• cites [40] Lin, 2019, Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease, J Neuroinflamm sourcePartly supported

  The Results section on altered cytokine responses reports a correlation between Bacteroides abundance and plasma TNFα in patients with Parkinson’s disease, and the Discussion identifies the study population as Asian. It also reports a correlation with plasma IFNγ, but for Verrucomicrobia—not Verrucomicrobiaceae, the different taxonomic group named in the claim. Page numbers are unavailable in our copy. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

Autoimmunity may play a role in the pathogenesis of Parkinson's disease, although it is unclear whether alpha-synuclein antibodies are pathogenic.

“These findings suggest that autoimmunity may play a role in the pathogenesis of Parkinson's disease, although it is unclear yet whether a-synuclein antibodies are pathogenic.”

• cites [96] Akhtar, 2018, Measurements of auto-antibodies to alpha-synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease, J Neurochem sourceSupported

May combine two claims.

TLR2 gene-deficient mice had significantly reduced enteric neurons and glial cells and showed stronger colonic inflammation in response to external stimulation.

“Researchers observed that TLR2 gene-deficient (Tlr2 -/-) mice had significantly reduced enteric neurons and glial cells and showed stronger colonic inflammation in response to external stimulation.118”

• cites [118] Brun, 2013, Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system, Gastroenterology sourceSupported

May combine two claims.

In a mouse model, gastric infection by Helicobacter suis resulted in gastric inflammation and increased gastrointestinal permeability, accompanied by an increased level of proinflammatory cytokines in serum, which was associated with systemic inflammation.

“In a mouse model, it was found that gastric infection by Helicobacter suis resulted in gastric inflammation and increased gastrointestinal permeability, accompanied by an increased level of proinflammatory cytokines in serum, which was associated with systemic inflammation.107”

• cites [107] Gorle, 2018, The choroid plexus epithelium as a novel player in the stomach-brain axis during Helicobacter infection, Brain Behav Immun sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Intranasal injection of LPS activates microglia in the olfactory bulb and substantia nigra through IL-1b/IL-1R1 signalling, increases pS129 a-synuclein-positive cells in the olfactory bulb and substantia nigra and reduces the number of TH-immunoreactive cells, suggesting loss of dopaminergic cells.

“In animal experiments, intranasal injection of LPS could activate microglia in the olfactory bulb and substantia nigra through IL-1b/IL-1R1 signalling, increase pS129 a-synucleinpositive cells in the olfactory bulb and substantia nigra and reduce the number of tyrosine hydroxylase (TH)-immunoreactive cells, suggesting the loss of dopaminergic cells.150”

• cites [150] Niu, 2020, IL-1beta/IL-1R1 signaling induced by intranasal lipopolysaccharide infusion regulates alpha-synuclein pathology in the olfactory bulb, substantia nigra and striatum, Brain Pathol sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Vagotomy was not associated with the risk of Parkinson's disease in a Swedish study with follow-up of patients after vagotomy.

“In contrast, another study with a follow-up of patients after vagotomy argued that vagotomy was not associated with the risk of Parkinson's disease in Sweden.144”

• cites [144] Liu, 2017, Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study, Neurology sourceSupported

May combine two claims.

Germ-free animals display global deficiency in microglia and reduced genes needed to express type I interferon receptors such as Jak3 and Stat1.

“Erny et al. 147 illustrated that germ-free animals display global deficiency in microglia and the genes needed to express type I interferon receptors such as Janus kinase 3 (Jak3) and signal transducer and activator of transcription 1 (Stat1), were reduced.147”

• cites [147] Erny, 2015, Host microbiota constantly control maturation and function of microglia in the CNS, Nat Neurosci sourcePartly supported

  In “Germ-free animals display global defects in microglia,” the paper reports reduced Jak3 and Stat1 expression in germ-free microglia and describes broad defects in their maturation and function. It does not report a global deficiency in microglial cell numbers: it found significantly more microglia in every brain region investigated. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Lipopolysaccharide produced by gut microbiota treatment can increase the accumulation of alpha-synuclein in the enteric nervous system and increase intestinal permeability.

“LPS produced by gut microbiota treatment can increase the accumulation of a-synuclein in the enteric nervous system and increase intestinal permeability.128”

• cites [128] Kelly, 2014, Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson's disease, Mov Disord sourcePartly supported

  The Discussion reports that low-dose LPS increased enteric α-synuclein expression and gut permeability in mice, predominantly in the large intestine. But the Experimental Design specifies a single intraperitoneal LPS dose, not treatment with gut microbiota or a demonstration that microbiota-produced LPS caused these effects. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

The function of microglia can be restored by reconstruction of gut microbiota or their metabolites, indicating that microbiota may be involved in the activity of the innate immune system in the brain via microbial metabolites and intestinal secretions.

“The function of microglia can be restored by the reconstruction of gut microbiota or their metabolites, indicating that microbiota may also be involved in the activity of the innate immune system in the brain via microbial metabolites and intestinal secretions.147”

• cites [147] Erny, 2015, Host microbiota constantly control maturation and function of microglia in the CNS, Nat Neurosci sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Exposure to curli-producing bacteria increases the deposition and accumulation of a-synuclein in intestinal ganglion cells and the brain, and increases the inflammatory response in the brain.

“Exposure to curli-producing bacteria increases the deposition and accumulation of a-synuclein in intestinal ganglion cells (myenteric plexus and submucosa) and the brain, respectively, as well as increasing the inflammatory response in the brain.131”

• cites [131] Chen, 2016, Exposure to the functional bacterial amyloid protein curli enhances alpha-synuclein aggregation in aged Fischer 344 rats and Caenorhabditis elegans, Sci Rep sourceSupported

May combine two claims.

Serum LPS-binding protein level in patients with Parkinson's disease is lower than in controls, indicating that increased intestinal permeability and increased invasion of Gram-negative bacteria leads to an increase in LPS in the circulatory system.

“A clinical study revealed that the level of serum LPS-binding protein in patients with Parkinson's disease was lower than that in controls, indicating that increased intestinal permeability and increased invasion of Gram-negative bacteria leads to an increase in LPS in the circulatory system.148”

• cites [148] Hasegawa, 2015, Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson's disease, PLoS One sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Peripheral inflammation induced by systemic LPS administration increases activation of microglia and proinflammatory cytokines, destroys the BBB, and aggravates polarization of the A1 phenotype of astrocytes and loss of dopamine neurons in the substantia nigra and striatum of MPTP mice.

“The peripheral inflammation induced by systemic LPS administration increased the activation of microglia and proinflammatory cytokines, destroyed the BBB, and aggravated the polarization of the A1 phenotype of astrocytes and the loss of dopamine neurons in the substantia nigra and striatum of MPTP mice.149”

• cites [149] Garcia-Dominguez, 2018, Peripheral inflammation enhances microglia response and nigral dopaminergic cell death in an in vivo MPTP model of Parkinson's disease, Front Cell Neurosci sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

A recent study did not find pathological damage to a-synuclein in the vagus nerve in an animal model of Parkinson's disease, which does not support the hypothesis that a-synuclein pathology is transmitted through the vagus nerve and the dorsal motor nucleus of the vagus nerve.

“Remarkably, a recent study did not find pathological damage to a-synuclein in the vagus nerve in an animal model of Parkinson's disease, which does not support the hypothesis that a-synuclein pathology is transmitted through the vagus nerve and the dorsal motor nucleus of the vagus nerve.140”

• cites [140] Arotcarena, 2020, Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates, Brain sourceSupported

May combine two claims.

Increased intestinal permeability is associated with increased bacteria and exposure to the bacterial endotoxin in Parkinson's disease, while increased intestinal alpha-synuclein and 3-nitrotyrosine staining (associated with oxidative stress) leads to high intestinal permeability.

“Increased intestinal permeability is associated with increased bacteria and exposure to the bacterial endotoxin in Parkinson's disease, while increased intestinal a-synuclein and 3nitrotyrosine staining (associated with oxidative stress) leads to high intestinal permeability.127”

• cites [127] Forsyth, 2011, Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease, PLoS One sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Wild-type mice lacking gut microbiota also have enteric nervous system and GDNF deficiencies, which can be partially repaired by administration of TLR2 agonists.

“Furthermore, similar to Tlr2 -/-mice, the wild-type mice lacking gut microbiota also have enteric nervous system and GDNF deficiencies, which can be partially repaired by administration of TLR2 agonists.118”

• cites [118] Brun, 2013, Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system, Gastroenterology sourceSupported

May combine two claims.

Activation of neuronal TLR2 in the brains of patients with Parkinson's disease results in increased proinflammatory cytokine TNF levels and recruitment of microglia to amplify neuroinflammation as well as increased expression of a-synuclein.

“The activation of neuronal TLR2 in the brains of patients with Parkinson's disease results in increased proinflammatory cytokine (TNF) levels and recruitment of microglia to amplify neuroinflammation as well as increased expression of asynuclein.158”

• cites [158] Dzamko, 2017, Toll-like receptor 2 is increased in neurons in Parkinson's disease brain and may contribute to alpha-synuclein pathology, Acta Neuropathol sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Butyrate protects cells from increased paracellular permeability and destruction of the epithelial barrier by LPS, increases expression of tight junction claudins by activating the Akt/mTOR signalling pathway and downregulates expression of TLR4 to decrease expression of inflammatory cytokines.

“Butyrate can protect cells from increased paracellular permeability and destruction of the epithelial barrier by LPS, increase the expression of tight junction claudins by activating the Akt/mTOR signalling pathway and downregulate the expression of TLR4 to decrease the expression of the inflammatory cytokines.191”

• cites [191] Koval, 2017, Butyrate modifies intestinal barrier function in IPEC-J2 cells through a selective upregulation of tight junction proteins and activation of the Akt signaling pathway, PLoS One sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Propionate increases the survival rate of TH+ dopaminergic neurons in rotenone-treated dopaminergic neurons, increases expression of the TH gene, decreases expression of the a-synuclein gene, and increases expression of intracellular STAT3 protein to promote neuroprotection.

“A recent study on the effect of propionate on rotenone-treated dopaminergic neurons showed that the survival rate of TH + dopaminergic neurons increased significantly, indicating that propionic acid increased the expression of the TH gene, decreased the expression of the a-synuclein gene, and increased the expression of intracellular STAT3 protein to promote neuroprotection.197”

• cites [197] Ostendorf, 2020, Propionic acid and fasudil as treatment against rotenone toxicity in an in vitro model of Parkinson's disease, Molecules sourcePartly supported

  Results §§2.2–2.4 report significantly greater TH+ cell survival with propionic acid under rotenone, increased TH gene expression, and increased STAT3 protein expression. But Results §2.3 reports that propionic acid significantly increased—not decreased—aSyn gene expression relative to the untreated control. The Discussion (§3) also says STAT3 signaling showed no robust modification, so the paper does not establish increased STAT3 as the mechanism of neuroprotection. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

The integrity of the BBB in germ-free mice is enhanced by transplanting faecal microbiota from pathogen-free mice or by using microbial SCFAs, suggesting that microbiota can regulate the function of the BBB.

“The integrity of the BBB in germ-free mice was enhanced by transplanting faecal microbiota from the pathogen-free mice or by using microbial SCFAs, suggesting that the microbiota can regulate the function of the BBB.167”

• cites [167] Braniste, 2014, The gut microbiota influences blood-brain barrier permeability in mice, Sci Transl Med sourceSupported

May combine two claims.

Bile acids can eliminate bacterial overgrowth and reduce bacterial translocation and endotoxemia.

“Bile acids can, moreover, eliminate bacterial overgrowth and reduce bacterial translocation and endotoxemia.208”

• cites [208] Lorenzo-Zuniga, 2003, Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats, Hepatology sourcePartly supported

  The Abstract (p. 551) reports that oral conjugated bile acids eliminated intestinal bacterial overgrowth and decreased bacterial translocation and endotoxemia in ascitic cirrhotic rats. The citing sentence omits that experimental population and the fact that the administered bile acids were conjugated, making the claim broader than the result shown. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

SCFAs are associated with a variety of diseases such as rectal cancer, pancreatitis, abnormal energy metabolism, constipation, blood lipid metabolism, sleep disorders and Alzheimer's disease.

“Studies have found that SCFAs are associated with a variety of diseases such as rectal cancer, 174 pancreatitis, 175 abnormal energy metabolism, 176 constipation, 177 blood lipid metabolism, 178 sleep disorders 179 and Alzheimer's disease.180”

• cites [174] Ma, 2020, Sodium butyrate modulates gut microbiota and immune response in colorectal cancer liver metastatic mice, Cell Biol Toxicol sourceNot checked — no full text of the source
• cites [175] Pan, 2019, Butyrate ameliorates caerulein-induced acute pancreatitis and associated intestinal injury by tissue-specific mechanisms, Br J Pharmacol sourceSupported
• cites [176] Li, 2018, Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit, Gut sourceSupported
• cites [177] Tian, 2021, Analysis of gut microbiome and metabolite characteristics in patients with slow transit constipation, Dig Dis Sci sourceNot checked — no full text of the source
• cites [178] Tayyeb, 2020, Short-chain fatty acids (except hexanoic acid) lower NF-kB transactivation, which rescues inflammation-induced decreased apolipoprotein A-I transcription in HepG2 cells, Int J Mol Sci sourceSupported
• cites [179] Szentirmai, 2019, Butyrate, a metabolite of intestinal bacteria, enhances sleep, Sci Rep sourcePartly supported

  Citation 179 is attached to “sleep disorders,” not the other conditions in the list. The Introduction and Discussion (page unavailable) report that butyrate, an SCFA, increased sleep in mice and rats. They do not establish an association with sleep disorders, so the cited evidence supports a link to sleep but not the disease-specific claim. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [180] Ho, 2018, Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer's disease-type beta-amyloid neuropathological mechanisms, Expert Rev Neurother sourceSupported

May combine two claims.

Pathological a-synuclein aggravates the progression of Parkinson's disease by activating microglia, while absence or overstimulation of microglia can affect the spread of a-synuclein in the brain.

“Pathological a-synuclein aggravates the progression of Parkinson's disease by activating microglia, while the absence or overstimulation of microglia can affect the spread of a-synuclein in the brain.153,159”

• cites [153] Zhang, 2017, Pathological alpha-synuclein exacerbates the progression of Parkinson's disease through microglial activation, Toxicol Lett sourceNot checked — no full text of the source
• cites [159] George, 2019, Microglia affect α-synuclein cell-to-cell transfer in a mouse model of Parkinson’s disease, Mol Neurodegener sourcePartly supported

  The Abstract Conclusions (page not provided) state that microglial absence or hyperstimulation affected α-synuclein transfer in the brain. The Background says aggregated α-synuclein activates microglia and that neuroinflammation can worsen neuropathology in animal models of Parkinson’s disease. It does not establish the stronger claim that this mechanism aggravates disease progression in patients. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

Increased activation of TNF/TNFR1 signalling following chronic activation of microglia can give rise to TNF-mediated necroptotic neuronal cell death, representing a possible therapeutic target in Parkinson's disease.

“Increased activation of TNF/TNFR1 signalling following chronic activation of microglia can give rise to TNF-mediated necroptotic neuronal cell death, 160 which represents a possible therapeutic target in Parkinson's disease.161”

• cites [160] Iannielli, 2018, Pharmacological inhibition of necroptosis protects from dopaminergic neuronal cell death in Parkinsons disease models, Cell Reports sourceSupported
• cites [161] Yuan, 2019, Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases, Nat Rev Neurosci sourcePartly supported

  The Introduction describes TNFR1-triggered necroptosis, and the section on mitochondrial and lysosomal defects reports evidence implicating necroptosis in Parkinson’s disease, including protective effects of RIPK1 inhibition in disease models (page numbers unavailable). The copy does not establish the claimed sequence in Parkinson’s disease—chronic microglial activation increasing TNF/TNFR1 signalling and thereby causing necroptotic neuronal death. Its discussion of chronic microglial inflammation and TNF concerns Alzheimer’s disease. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Butyrate promotes production of IL-10 by regulating differentiation of Th1 and Th17 cells and inducing expression of Blimp1, ameliorating colonic inflammation and maintaining intestinal homeostasis.

“Butyrate can also promote the production of IL-10 by regulating the differentiation of Th1 and Th17 cells and inducing the expression of mature protein 1 (Blimp1), ameliorating colonic inflammation and maintaining intestinal homeostasis.189”

• cites [189] Chen, 2019, Microbiota metabolite butyrate differentially regulates Th1 and Th17 cells' differentiation and function in induction of colitis, Inflamm Bowel Dis sourceSupported

May combine two claims.

SCFAs can reduce degeneration of dopaminergic neurons and improve dyskinesia in a rotenone-induced Drosophila Parkinson's disease model.

“SCFAs may be able to modulate neuroinflammation in (HDACi), can reduce the degeneration of dopaminergic neurons and improve dyskinesia in a rotenone-induced Drosophila Parkinson's disease model.194”

• cites [194] St. Laurent, 2013, Sodium butyrate improves locomotor impairment and early mortality in a rotenone-induced Drosophila model of Parkinson's disease, Neuroscience sourcePartly supported

  The Abstract and Discussion (pages unavailable) report that sodium butyrate improved rotenone-induced locomotor impairment in Drosophila and was associated with higher brain dopamine levels. They do not report reduced dopaminergic-neuron degeneration in the rotenone model; the Abstract attributes that effect to sodium butyrate in a different, α-synuclein Drosophila model. The study also tested sodium butyrate, not SCFAs as a group, and measured locomotor impairment rather than dyskinesia. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

FMT has been regarded as an effective and safe treatment for patients with recurrent C. difficile and has been approved by the Federal Drug Administration in the USA.

“FMT has been regarded as an effective and safe treatment for patients with recurrent C. difficile and has been approved by the Federal Drug Administration in the USA.266”

• cites [266] Carlucci, 2016, Fecal microbiota-based therapeutics for recurrent Clostridium difficile infection, ulcerative colitis and obesity, EBioMedicine sourcePartly supported

  The FMT section reports about 90% clinical cure of recurrent C. difficile infection, supporting the effectiveness claim. The Regulation of Stool-based Therapeutics section says the FDA allows FMT for this use under specified conditions without an Investigational New Drug application; it does not say the FDA approved it. That section also calls for monitoring long-term safety and adverse events, so the unqualified safety claim is not established. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

May combine two claims.

The mechanisms of probiotics in Parkinson's disease may involve relieving symptoms, inhibiting inflammation, avoiding antioxidant stress and neuronutrition.

“although the mechanisms may involve relieving symptoms, inhibiting inflammation, avoiding antioxidant stress and neuronutrition.254,255”

• cites [254] Castelli, 2020, Effects of the probiotic formulation SLAB51 in and Parkinson's disease models, Aging (Albany NY sourceSupported
• cites [255] Tamtaji, 2019, Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trial, Clin Nutr sourcePartly supported

  Section 4.1 reports improved Parkinson’s symptom scores and markers of inflammation and oxidative stress after probiotic supplementation, and discusses possible pathways for those effects. It also mentions effects on central neurochemistry, but does not describe a neuronutrition mechanism. No page number is available in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The composition of the intestinal microbiota could affect different organ systems, including the cardiovascular, nervous, immune and metabolic systems.

“The composition of the intestinal microbiota could affect different organ systems, including the cardiovascular, nervous, immune and metabolic systems.251”

• cites [251] Azad, 2018, Probiotic species in the modulation of gut microbiota: An overview, Biomed Res Int sourceSupported

May combine two claims.

Roseburia intestinalis decreased the disease activity index score, intestinal mucosal epithelial injury and mucosal lymphocyte infiltration, while inhibiting intestinal inflammation, by increasing the number of Treg cells and the expression of anti-inflammatory cytokines in a mouse model of colitis.

“In addition, recent studies have reported that Roseburia intestinalis decreased the disease activity index score, intestinal mucosal epithelial injury and mucosal lymphocyte infiltration, while inhibiting intestinal inflammation, by increasing the number of Treg cells and the expression of anti-inflammatory cytokines in a mouse model of colitis.272,273”

• cites [272] Shen, 2018, Insights into Roseburia intestinalis which alleviates experimental colitis pathology by inducing anti-inflammatory responses, J Gastroenterol Hepatol sourceNot checked — no full text of the source
• cites [273] Zhu, 2018, Roseburia intestinalis inhibits interleukin17 excretion and promotes regulatory T cells differentiation in colitis, Mol Med Rep sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

The main olive oil polyphenols, hydroxytyrosol and oleuropein aglycone, can reduce accumulation of a-synuclein in muscle cells and prevent neurodegeneration of dopaminergic neurons containing a-synuclein in Caenorhabditis elegans Parkinson's disease models.

“A recent study in Caenorhabditis elegans Parkinson's disease models showed that the main olive oil polyphenols, hydroxytyrosol and oleuropein aglycone, can reduce the accumulation of a-synuclein in muscle cells and prevent the neurodegeneration of dopaminergic neurons containing a-synuclein.248”

• cites [248] Brunetti, 2020, Healthspan Maintenance and Prevention of Parkinson's-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans, Int J Mol Sci sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Prebiotics (including galacto- and fructooligosaccharides) can effectively normalize motor and nonmotor abnormalities and restore the level of dopamine transporters in the striatum induced by rotenone.

“Studies have shown that prebiotics (including galacto-and fructooligosaccharides) can effectively normalize motor and nonmotor abnormalities and restore the level of dopamine transporters in the striatum induced by rotenone.258”

• cites [258] Perez-Pardo, 2017, Promising effects of neurorestorative diets on motor, cognitive, and gastrointestinal dysfunction after symptom development in a mouse model of Parkinson's disease, Front Aging Neurosci sourcePartly supported

  The Abstract and Discussion report that Diet2 improved rotenone-induced motor and nonmotor abnormalities and restored striatal dopamine transporter (DAT) levels in mice. The Diets table shows that Diet2 contained galacto- and fructooligosaccharides, but also uridine, fatty acids, vitamins, and other nutrients. The study did not isolate the effects of prebiotics, so it cannot establish that prebiotics themselves produced those outcomes. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

Gut microbiota plays a key role in promoting serotonin secretion, inducing enteric nervous system maturation by releasing 5-HT and activating the 5-HT4 receptor.

“The gut microbiota plays a key role in promoting serotonin secretion, inducing enteric nervous system maturation by releasing 5-HT and activating the 5-HT4 receptor.222”

• cites [222] De Vadder, 2018, ut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks, Proc Natl Acad Sci U S A sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Higher compliance with the Mediterranean diet is associated with lower risk of Parkinson's disease and lower score of the Mediterranean diet with earlier age of onset of Parkinson's disease, but it is not indicated whether low Mediterranean dietary compliance is the result or cause of Parkinson's disease.

“A case-control study reported that the higher the compliance with a Mediterranean diet, the lower the risk of Parkinson's disease and the lower the score of the Mediterranean diet, the earlier the age of onset of Parkinson's disease, but it did not indicate whether low Mediterranean dietary compliance was the result or cause of Parkinson's disease.236”

• cites [236] Alcalay, 2012, The association between Mediterranean diet adherence and Parkinson's disease, Mov Disord sourceSupported

May combine two claims.

The exact mechanisms and safety of using probiotics in Parkinson's disease have not fully been clarified.

“However, the exact mechanisms and safety of using probiotics in Parkinson's disease have not fully been clarified, although the mechanisms may involve relieving symptoms, inhibiting inflammation, avoiding antioxidant stress and neuronutrition.254,255”

• cites [254] Castelli, 2020, Effects of the probiotic formulation SLAB51 in and Parkinson's disease models, Aging (Albany NY sourcePartly supported

  The Discussion and Conclusion (page not provided) describes the proposed PPARγ mechanism as speculative and calls for further study, supporting the claim that probiotic mechanisms in Parkinson’s disease are not fully clarified. The paper studies SLAB51 in cell and animal models, but the passages do not assess or discuss the safety of probiotic use in people with Parkinson’s disease. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [255] Tamtaji, 2019, Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trial, Clin Nutr sourcePartly supported

  The Discussion (sections 4.1–4.2; page unavailable) proposes possible mechanisms and says further work on gene expression could help identify them, supporting the point that mechanisms remain unclear. The Results (section 3; page unavailable) report no side effects during the 12-week trial, but the paper does not state that the safety of probiotics in Parkinson’s disease remains unclarified. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The endoscopic index of Crohn's disease severity decreased 6 weeks after FMT in a recent randomized, single-blind and controlled trial.

“The results of a recent randomized, single-blind and controlled trial demonstrated that the endoscopic index of Crohn's disease severity decreased 6 weeks after FMT.267”

• cites [267] Sokol, 2020, Fecal microbiota transplantation to maintain remission in Crohn's disease: A pilot randomized controlled study, Microbiome sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Doctors have a relatively high awareness and acceptance of FMT but are most concerned about patients' acceptance of the treatment, followed by a lack of guidelines and ethical constraints.

“A survey ascertained that doctors have a relatively high awareness and acceptance of FMT but are most concerned about patients' acceptance of the treatment, followed by a lack of guidelines and ethical constraints.280”

• cites [280] Ren, 2016, Chinese physicians' perceptions of faecal microbiota transplantation, World J Gastroenterol sourceSupported

May combine two claims.

Microbiota play an important role in α-synuclein production and neuroinflammation.

“Moreover, the increased production of cytokines in the midbrain and colon indicates that microbiota play an important role in a-synuclein production and neuroinflammation.132”

• cites [132] Sampson, 2020, A gut bacterial amyloid promotes alpha-synuclein aggregation and motor impairment in mice, Elife sourcePartly supported

  The Results and discussion section reports increased cytokine production in the midbrain and colon of mice colonized with curli-producing E. coli, supporting the neuroinflammation part of the claim. It reports increased α-synuclein aggregation despite similar transgene production, so these findings do not establish increased α-synuclein production. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

The double-hit hypothesis proposed by Hawkes et al. supports their theory, pointing out that α-synuclein pathology is transmitted to the midbrain through two different routes, namely, from the nasal cavity to the temporal lobe or from the stomach, followed by nasal secretions in swallowed saliva.

“The double-hit hypothesis proposed by Hawkes et al.135 supports their theory, pointing out that a-synuclein pathology is transmitted to the midbrain through two different routes, namely, from the nasal cavity to the temporal lobe or from the stomach, followed by nasal secretions in swallowed saliva.135”

• cites [135] Hawkes, 2007, Parkinson's disease: A dual-hit hypothesis, Neuropathol Appl Neurobiol sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Colonization of curli-producing E. coli in α-synuclein-overexpressing mice aggravated motility injury and gastrointestinal dysfunction, while promoting the accumulation and inflammatory response of α-synuclein in the intestine and brain, resulting in increased expression of proinflammatory cytokines IL-6 and TNF in brain-derived CD11b+ microglia.

“Colonization of curli-producing E. coli in a-synuclein-overexpressing mice aggravated motility injury and gastrointestinal dysfunction, while promoting the accumulation and inflammatory response of a-synuclein in the intestine and brain, resulting in increased expression of the proinflammatory cytokines IL-6 and TNF in brain-derived CD11b + microglia.132”

• cites [132] Sampson, 2020, A gut bacterial amyloid promotes alpha-synuclein aggregation and motor impairment in mice, Elife sourceSupported

May combine two claims.

In a patient with Parkinson's disease with constipation, constipation and movement symptoms were significantly relieved after a single FMT treatment, and leg tremor almost disappeared 1 week after FMT treatment.

“A clinical study reported that constipation and movement symptoms were significantly relieved after a single FMT treatment in a patient with Parkinson's disease with constipation, and leg tremor almost disappeared 1 week after FMT treatment.277”

• cites [277] Huang, 2019, Fecal microbiota transplantation to treat Parkinson's disease with constipation: A case report, Medicine (Baltimore sourcePartly supported

  The Case presentation reports that leg tremor almost disappeared one week after FMT, the UPDRS score decreased significantly, and constipation was significantly alleviated. But it also says the fecal suspension was administered three times, once daily, rather than as a single administration. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The duration and recovery time of the alterations in gut microbiota caused by antibiotics seem uncertain.

“Thus, the duration and recovery time of the alterations in gut microbiota caused by antibiotics seem uncertain.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Study findings on gut microbiota in Parkinson's disease vary due to differences in methodology, geographical regions, age and dietary habits.

“The study findings vary due to differences in methodology, geographical regions, age and dietary habits.”

May combine two claims.

The abundance of gut microbiota in patients with Parkinson's disease is significantly altered and has obvious characteristics.

“In summary, the abundance of gut microbiota in patients with Parkinson's disease is significantly altered and has obvious characteristics, which may be used as potential”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Akkermansia muciniphila may have beneficial effects on metabolic disorders in obese mice as well as metabolic syndrome lipid metabolism.

“Akkermansia muciniphila may also have beneficial effects on metabolic disorders in obese mice as well as metabolic syndrome lipid metabolism.45”

• cites [45] Everard, 2013, Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity, Proc Natl Acad Sci U S A sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In 12 healthy males treated with a 4-day antibiotic intervention, the composition of gut microbiota returned to initial baseline within 1.5 months.

“Another study analysed the alteration of gut microbiota in 12 healthy males treated with 4-day antibiotic intervention and found that the composition of gut microbiota returned to initial baseline within 1.5 months.54”

• cites [54] Palleja, 2018, Recovery of gut microbiota of healthy adults following antibiotic exposure, Nat Microbiol sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Parkinson's disease is a common neurodegenerative disease largely characterized by the loss of dopaminergic neurons with abnormal accumulation of alpha-synuclein in the substantia nigra and striatum.

“Parkinson's disease is a common neurodegenerative disease largely characterized by the loss of dopaminergic neurons with abnormal accumulation of a-synuclein in the substantia nigra and striatum.”

May combine two claims.

In rotenone-induced Parkinson's disease mice, in the caecal mucosa, the relative abundance of Bacteroidetes and Firmicutes significantly increased in the experimental group, whereas the relative abundance of Actinobacteria and beneficial symbiotic bacteria Bifidobacterium significantly decreased.

“A study on the composition of caecal mucosa-associated and luminal microbiota in rotenoneinduced Parkinson's disease mice showed that in the caecal mucosa, the relative abundance of the phyla Bacteroidetes and Firmicutes significantly increased in the experimental group, whereas the relative abundance of Actinobacteria and beneficial symbiotic bacteria Bifidobacterium significantly decreased.49”

• cites [49] Perez-Pardo, 2018, Gut bacterial composition in a mouse model of Parkinson’s disease, Beneficial Microb sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

The composition of gut microbiota is affected by antibiotics, leading to imbalance of host immune homeostasis and increased susceptibility to disease.

“Several lines of evidence in recent studies have shown that the composition of gut microbiota is affected by antibiotics, leading to the imbalance of host immune homeostasis and increased susceptibility to disease.”

May combine two claims.

Altered gut microbiota in Parkinson's disease may be used as potential biomarkers or therapeutic targets.

“which may be used as potential biomarkers or therapeutic targets.”

May combine two claims.

Most antibiotics interfere with the composition and enzyme activity of the intestinal microbiota and inhibit enzyme activity.

“Most antibiotics interfere with the composition and enzyme activity of the intestinal microbiota and inhibit enzyme activity.52”

• cites [52] Kim, 2015, Gut microbiota-mediated drug-antibiotic interactions, Drug Metab Dispos sourceNot checked — no full text of the source

May combine two claims.

Clinical evidence has demonstrated a relationship between gut microbiota, clinical symptoms including motor and non-motor symptoms, and disease stage in Parkinson's disease.

“In recent years, clinical evidence has demonstrated the relationship between gut microbiota, clinical symptoms (including motor and non-motor symptoms) and disease stage in Parkinson's disease.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Metabolic syndrome, including insulin resistance and obesity, is an essential risk factor for cognitive impairment and dementia disorders.

“Campos-Peña et al. 46 reported that metabolic syndrome, including insulin resistance and obesity, is an essential risk factor for cognitive impairment and dementia disorders.46”

• cites [46] Campos-Peña, 2017, Metabolic syndrome as a risk factor for Alzheimer's disease: Is Aβ a crucial factor in both pathologies?, Antioxid Redox Signal sourceNot checked — no full text of the source

May combine two claims.

Antibiotic administration in specific pathogen-free mice temporarily altered the composition of the microbiota with a significant increase in Firmicutes and Actinobacteria and a decrease in Bacteroidetes and Proteobacteria and increased exploratory behaviour.

“Antibiotic administration in specific pathogen-free mice temporarily altered the composition of the microbiota with a significant increase in Firmicutes and Actinobacteria and a decrease in Bacteroidetes and Proteobacteria and increased exploratory behaviour.55”

• cites [55] Bercik, 2011, The intestinal microbiota affect central levels of brain-derived neurotropic factor and behaviour in mice, Gastroenterology sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

The results of studies on animal models of Parkinson's disease are similar to those in humans.

“The results of the studies on animal models of Parkinson's disease are similar to those in humans.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Although studies suggest that the microbiota is associated with the pathogenesis of Parkinson's disease, the specific mechanisms have not fully been elucidated.

“Although studies suggest that the microbiota is associated with the pathogenesis of Parkinson's disease, the specific mechanisms have not fully been elucidated.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The myenteric plexus regulates muscle activity, while the submucosal plexus participates in mucosal function.

“The myenteric plexus regulates muscle activity, while the submucosal plexus participates in mucosal function.”

May combine two claims.

Microbial metabolism and associated metabolites regulate the homeostasis of the gut and affect the development of the CNS and Parkinson's disease by regulating the intestinal barrier, drug interactions, neurotrophic factors and the immune response.

“Microbial metabolism and the associated metabolites regulate the homeostasis of the gut and affect the development of the CNS and Parkinson's disease by regulating the intestinal barrier, drug interactions, neurotrophic factors and the immune response.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The enteric nervous system is a relay station between the gut microbiota and brain and is one of the three branches of the autonomic nervous system (sympathetic, parasympathetic and enteric).

“The enteric nervous system is a relay station between the gut microbiota and brain and is one of the three branches of the autonomic nervous system (sympathetic, parasympathetic and enteric).69”

• cites [69] Rao, 2016, The bowel and beyond: The enteric nervous system in neurological disorders, Nat Rev Gastroenterol Hepatol sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Because of different dietary structures in different countries and regions, the composition of gut microbiota is also different.

“Because of the different dietary structures in different countries and regions, the composition of gut microbiota is also different.”

May combine two claims.

Patients with Parkinson's disease and irritable bowel syndrome-like symptoms (abdominal pain) had more non-motor symptoms, along with lower levels of Prevotella (genus and family).

“Patients with Parkinson's disease and irritable bowel syndrome-like symptoms (abdominal pain) had more non-motor symptoms, along with lower levels of Prevotella (genus and family)”

• cites [58] Mertsalmi, 2017, More than constipation - Bowel symptoms in Parkinson's disease and their connection to gut microbiota, Eur J Neurol sourceNot checked — no full text of the source

May combine two claims.

The positive rate of small intestinal bacterial overgrowth in patients with Parkinson's disease is significantly increased, and it is associated with deterioration of gastrointestinal symptoms and motor function.

“Recently, the positive rate of small intestinal bacterial overgrowth in patients with Parkinson's disease was found to be significantly increased, and it was associated with the deterioration of gastrointestinal symptoms and motor function.61”

• cites [61] Niu, 2016, Prevalence of small intestinal bacterial overgrowth in Chinese patients with Parkinson's disease, J Neural Transm (Vienna) sourceNot checked — no full text of the source

May combine two claims.

Most studies on gut microbiota in Parkinson's disease have been cross-sectional, involving different selected populations and research methods, with no data on the relationship between the composition of specific gut microbiota and disease progression.

“However, most studies have been cross-sectional, involving different selected populations and research methods, with no data on the relationship between the composition of specific gut microbiota and disease progression.”

Probably not a substantial claim: may not pass S3 (load-bearing).

It remains unclear whether the peripheral immune response is the cause or a result of CNS pathology in Parkinson's disease.

“it remains unclear whether the peripheral immune response is the cause or a result of CNS pathology.”

• cites [93] Liu, 2019, IL-17A exacerbates neuroinflammation and neurodegeneration by activating microglia in rodent models of Parkinson's disease, Brain Behav Immun sourceNot checked — no full text of the source

May combine two claims.