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Cited by 648Gut microbiota and healthGastrointestinal motility and disordersProbiotics and Fermented Foods

The Gut Microbiome and the Brain

Open access
Galland, Leo·2014·Journal of Medicinal Food
DOI 10.1089/jmf.2014.7000PMC PMC4259177
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Abstract

The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review argues that the human gut microbiome influences brain health through immunologic, biochemical, and neuroendocrine pathways, including endotoxin exposure, microbial metabolites, and vagus/enteric nervous system signaling. It concludes that the strongest human evidence for neurotoxic gut-derived effects is ammonia in hepatic encephalopathy and D-lactic acid in short bowel syndrome, while many other links remain speculative.

Key findings

  • The adult human body contains about 100 trillion bacteria with about 4 million distinct bacterial genes, more than 95% located in the large intestine; the adult gut is believed to contain about 1 gram of lipopolysaccharide (LPS).
  • In humans, parenteral LPS at 0.4 ng/kg body weight increases plasma IL-6, TNFα, IL-10, IL-1 receptor antagonist, cortisol, and norepinephrine, and is accompanied by depressed mood, increased anxiety, impaired long-term memory for emotional stimuli, and reduced visceral pain thresholds.
  • In hepatic encephalopathy, adding rifaximin to lactulose increases total reversal from 51% to 76% and reduces mortality from 49.1% to 23.8%; synbiotic regimens reduce serum ammonia and improve cognitive performance versus placebo.
  • Probiotic trials reviewed include a 30-day randomized, double-blind, placebo-controlled study in healthy French adults in which *Lactobacillus helveticus* R0052 plus *Bifidobacterium longum* R0175 reduced psychological distress on HSCL-90 and HADS and reduced urinary free cortisol; in chronic fatigue syndrome, a probiotic improved Beck Anxiety Inventory scores versus placebo.

Methods

  • Narrative review focusing on human research, with germ-free and conventional rodent studies used to illustrate evolutionary and developmental implications of the microbiome.
  • Synthesizes evidence across immunologic mechanisms, adaptive immunity, biochemical metabolites (D-lactic acid, ammonia, short-chain fatty acids), neuroendocrine signaling, and diet–microbiome interactions.
  • No systematic search strategy, inclusion criteria, or meta-analysis is described; evidence is drawn from clinical trials, animal models, case reports, and mechanistic studies.

Limitations

  • The paper states that the only mechanisms with a high level of proof in humans are the neurotoxic effects of ammonia in hepatic encephalopathy and of D-lactic acid in short bowel syndrome; other proposed links are speculative.
  • The paper states that there is almost no published research describing actual diet→microbiome→CNS effects in humans, and that autism findings do not yet permit a single coherent theory on which to base therapeutic decisions.
  • Evident from the text: this is a narrative review without systematic methods, relying on heterogeneous human studies, small trials, case reports, and animal models; substantial inter-individual microbiome variation limits generalization.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1089/jmf.2014.7000

Cites

161 of 161 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 128 cited sources checked · 0 supported · 0 flagged

  • Interpretationreasoning
    § Abstract

    Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation.

    “Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation.”
    Quote in the paperSubstantial claim
  • Premisecitation
    § Abstract

    Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity.

    “Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [100] MacFabe D. Autism: metabolism, mitochondria, and the microbiome. Global Adv Health Med 2013;2:52–66 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • Premisecitation
    § Abstract

    Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system.

    “Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Duerkop BA, Vaishnava S, Hooper LV: Immune responses to the microbiota at the intestinal mucosal surface. Immunity 2009;31:368–376 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • Premisecitation
    § Abstract

    Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia.

    “Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [60] Thurn JR, Pierpont GL, Ludvigsen CW, Eckfeldt JH: D-lactate encephalopathy. Am J Med 1985;79:717–721 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

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      Not checked in the free run.

  • Interpretationreasoning
    § Abstract

    The human gut microbiome impacts human brain health through multiple mechanisms.

    “The human gut microbiome impacts human brain health in numerous ways”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 15
  • May combine two claims. 52

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

    Premisenone given
    § Abstract

    Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system.

    “Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    Germ-free mice show greater exploratory activity in an open-field activity box than conventional mice, suggesting less vigilance and caution.

    “When compared with conventional mice, GF mice show greater exploratory activity in an open-field activity box, suggesting less vigilance and caution.11”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Diaz Heijtz R, Wang S, Anuar F, et al. : Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA 2011;108:3047–3052 [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    A study of germ-free mice found that the vast majority of chemicals circulating in blood are dependent on the microbiome for their synthesis, although many are subsequently modified by the host.

    “A study of germ-free (GF) mice found that the vast majority of chemicals circulating in blood are dependent on the microbiome for their synthesis, although many are subsequently modified by the host.8”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Wikoff WR, Anfora AT, Liu J, et al. : Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA 2009;106:3698–3703 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

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

    Premisenone given
    § Abstract

    Bacterial receptors for these hormones influence microbial growth and virulence.

    “Bacterial receptors for these hormones influence microbial growth and virulence.”
    Quote in the paperNot a substantial claim

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

    Premisenone given
    § Abstract

    Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans.

    “Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    The adult human body contains about one hundred trillion bacteria with about 4 million distinct bacterial genes, with more than 95% located in the large intestine.

    “The hundred trillion bacteria in the body of an adult human contain about 4 million distinct bacterial genes, with more than 95% of them located in the large intestine.4”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Qin J, Li R, Raes J, Arumugam M, et al. : A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010;464:59–65 [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Rice has about 46,000 functioning genes that evolved over 15 million years.

    “Rice (Oryza sativa), for example, has about 46,000 functioning genes that have evolved over 15 million years.2”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Jacquemin J, Ammiraju JS, Haberer G, et al. : Fifteen million years of evolution in the Oryza genus shows extensive gene family expansion. Mol Plant 2014;7:642–656 [DOI] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Germ-free mice show elevated striatal norepinephrine, dopamine, and serotonin turnover and elevated plasma ACTH and corticosterone in response to restraint stress, demonstrating heightened stress reactivity.

    “elevation of striatal norepinephrine, dopamine, and serotonin turnover in the brains of GF mice11 and elevated plasma levels of adrenal corticotrophic hormone and corticosterone in response to restraint stress13 demonstrate heightened stress reactivity in GF mice”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [11] Diaz Heijtz R, Wang S, Anuar F, et al. : Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA 2011;108:3047–3052 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [13] Sudo N, Chida Y, Aiba Y, et al. : Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 2004;558(Pt 1):263–275 [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Germ-free rats are less active and more cautious than conventional rats.

    “an effect also seen in GF rats, who are, however, less active and more cautious than conventional rats.14”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Crumeyrolle-Arias M, Jaglin M, Bruneau A, et al. : Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats. Psychoneuroendocrinology 2014;42:207–217 [DOI] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Developmental abnormalities found in germ-free mice are totally reversible by colonization with intestinal bacteria early in life but not in adulthood, suggesting that the microbiome influences brain development.

    “The developmental abnormalities found in GF mice are totally reversible by colonization with intestinal bacteria early in life but not in adulthood, suggesting that the microbiome influences brain development.9,10”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [9] Neufeld KM, Kang N, Bienenstock J, Foster JA: Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 2011;23:255–264, e119. [DOI] [PubMed] [Google Scholar] source

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    • cites [10] Diamond B, Huerta PT, Tracey K, Volpe BT: It takes guts to grow a brain: increasing evidence of the important role of the intestinal microflora in neuro- and immune-modulatory functions during development and adulthood. Bioessays 2011;33:588–591 [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Interpretationcitation
    § Introduction

    The gut microbiome can be viewed as an anaerobic bioreactor programmed to synthesize molecules that direct the mammalian immune system, modify the mammalian epigenome, and regulate host metabolism.

    “the gut microbiome can be viewed as an anaerobic bioreactor programmed to synthesize molecules which direct the mammalian immune system,5 modify the mammalian epigenome,6 and regulate host metabolism.7”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [5] Hooper LV: Bacterial contributions to mammalian gut development. Trends Microbiol 2004;12:129–134 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [6] Li M, Wang B, Zhang M, et al. : Symbiotic gut microbes modulate human metabolic phenotypes. PNAS 2008;105:2117–2122 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

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      Not checked in the free run.

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    Interpretationreasoning
    § Abstract

    Gut microbes influence memory, mood, and cognition.

    “They influence memory, mood, and cognition”
    Quote in the paperSubstantial claim

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    Interpretationreasoning
    § Introduction

    Both timidity in mice and aggressiveness in rats require a microbiome for their characteristic expression.

    “It appears that both timidity, a behavior pattern associated with mice, and aggressiveness, a behavior pattern associated with rats, require a microbiome for their characteristic expression.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Introduction

    The human gene pool contains about 26,000 functioning units.

    “about 26,000 functioning units1”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Venter JC, Adams MD, Myers EW, et al. : The sequence of the human genome. Science 2001;291:1304–1351 [DOI] [PubMed] [Google Scholar] source

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  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given
    § Abstract

    Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve.

    “Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning
    § Abstract

    Gut microbes are clinically and therapeutically relevant to alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome.

    “and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    LeClercq et al. reported increased intestinal permeability, elevated blood LPS and peptidoglycan levels, and low-grade systemic inflammation associated with psychological symptoms of alcohol dependence in alcohol-dependent subjects.

    “LeClercq et al.35 have reported increased intestinal permeability, elevated blood LPS and peptidoglycan levels, and low-grade systemic inflammation associated with psychological symptoms of alcohol dependence in alcohol-dependent subjects.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Leclercq S, De Saeger C, Delzenne N, et al. : Role of inflammatory pathways, blood mononuclear cells, and gut-derived bacterial products in alcohol dependence. Biol Psychiatry 2014;76:725–733 [DOI] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Visceral pain sensitivity thresholds are reduced and visceral pain is rated as more unpleasant after administration of low-dose LPS.

    “In addition, visceral pain sensitivity thresholds are reduced and visceral pain (provoked by rectal distension) is rated as more unpleasant after administration of low-dose LPS.28”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Benson S, Kattoor J, Wegner A, et al. : Acute experimental endotoxemia induces visceral hypersensitivity and altered pain evaluation in healthy humans. Pain 2012;153:794–799 [DOI] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    These changes are accompanied by depressed mood, increased anxiety, and impaired long-term memory for emotional stimuli.

    “These changes are accompanied by depressed mood, increased anxiety, and impaired long-term memory for emotional stimuli.27”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Grigoleit JS, Kullmann JS, Wolf OT, et al. : Dose-dependent effects of endotoxin on neurobehavioral functions in humans. PLoS One 2011;6:e28330. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

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    Premisecitation
    § Introduction

    Increased exposure to gut microbiome-derived LPS (endotoxemia) may occur in the elderly, in whom it is diminished by yogurt consumption.

    “Increased exposure to gut microbiome-derived LPS (endotoxemia) may occur in the elderly, in whom it is diminished by yogurt consumption,29”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Schiffrin EJ, Parlesak A, Bode C, et al. : Probiotic yogurt in the elderly with intestinal bacterial overgrowth: endotoxaemia and innate immune functions. Br J Nutr 2009;101:961–966 [DOI] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Balb/C mice become less stress reactive, and NIH Swiss mice become more stress reactive than their conventional counterparts after cross-colonization.

    “Balb/C mice become less stress reactive, and NIH Swiss mice become more stress reactive than their conventional counterparts.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Bercik P, Park AJ, Sinclair D, et al. : The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil 2011;23:1132–1139 [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    § Introduction

    The adult human gut is believed to contain about one gram of LPS.

    “The adult human gut is believed to contain about one gram of LPS.15”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Bested AC, Logan AC, Selhub EM: Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part II—contemporary contextual research. Gut Pathog 2013;5:3. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Interpretationreasoning
    § Introduction

    Loss of Bifidobacteria may play a pathogenetic role in celiac disease and contribute to its rising prevalence.

    “Loss of Bifidobacteria may play a pathogenetic role in CD and contribute to its rising prevalence.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    Researchers at Johns Hopkins University School of Medicine found evidence of increased gut bacterial translocation in schizophrenic patients, unrelated to antipsychotic treatment.

    “Researchers at Johns Hopkins University School of Medicine found evidence of increased gut bacterial translocation in schizophrenic patients, unrelated to antipsychotic treatment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Severance EG, Gressitt KL, Stallings CR, et al. : Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia. Schizophr Res 2013;148:130–137 [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisenone given
    § Introduction

    The adaptive immune system responds to specific microbes with antibodies or antigen-specific cellular immune responses and can produce CNS dysfunction through autoimmune reactions caused by molecular mimicry between bacterial and self proteins.

    “The adaptive immune system responds to specific microbes with antibodies or antigen-specific cellular immune responses and can produce CNS dysfunction through auto-immune reactions caused by molecular mimicry between bacterial and self proteins.”
    Quote in the paperNot a substantial claim

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    Interpretationreasoning
    § Introduction

    Altered exposure to structural components of the microbiome, which may occur because of increased intestinal permeability or SIBO, may disrupt normal neuroendocrine regulation and has been associated with several disorders linked to abnormal CNS function.

    “Altered exposure to structural components of the microbiome, which may occur because of increased intestinal permeability or SIBO, may disrupt normal neuroendocrine regulation and has been associated with several disorders linked to abnormal CNS function.”
    Quote in the paperSubstantial claim

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    Premisecitation
    § Introduction

    Small intestinal bacterial overgrowth is associated with fibromyalgia and restless legs syndrome.

    “SIBO is associated with fibromyalgia40 and restless legs syndrome (RLS),41”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [40] Wallace DJ, Hallegua DS: Fibromyalgia: the gastrointestinal link. Curr Pain Headache Rep 2004;8:364–368 [DOI] [PubMed] [Google Scholar] source

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    • cites [41] Weinstock LB, Fern SE, Duntley SP: Restless legs syndrome in patients with irritable bowel syndrome: response to small intestinal bacterial overgrowth therapy. Dig Dis Sci 2008;53:1252–1256 [DOI] [PubMed] [Google Scholar] source

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    Interpretationreasoning
    § Introduction

    The gut microbiome stimulates a chronic state of low-level activation of the innate immune system in humans, which is influenced by the circadian pattern of adrenal cortical function.

    “In summary, the gut microbiome stimulates a chronic state of low-level activation of the innate immune system in humans, which is influenced by the circadian pattern of adrenal cortical function.”
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    Premisenone given
    § Introduction

    The most common CNS manifestations of celiac disease are ataxia (with or without myoclonus), headache, and cognitive dysfunction.

    “The most common CNS manifestations of CD are ataxia (with or without myoclonus), headache, and cognitive dysfunction.”
    Quote in the paperNot a substantial claim

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    Premisecitation
    § Introduction

    Presence of the translocation marker soluble CD14 tripled the risk of schizophrenia and was positively associated with C-reactive protein but not with LPS-binding protein.

    “Presence of the translocation marker soluble CD14 tripled the risk of schizophrenia and was positively associated with C-reactive protein (CRP) but not with LPS-binding protein (LBP)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [42] Severance EG, Gressitt KL, Stallings CR, et al. : Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia. Schizophr Res 2013;148:130–137 [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    In healthy elderly men and women with depressed mood, 3 weeks of a probiotic beverage containing Lactobacillus casei improved mood but negatively impacted memory performance.

    “Those who began the study with depressed mood reported improved mood after 3 weeks of the probiotic but not the placebo beverage. Paradoxically, their memory performance was negatively impacted by the probiotic.130”
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    • cites [130] Benton D, Williams C, Brown A: Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr 2007;61:355–361 [DOI] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    SDR reduces the relative abundance of Bacteroides and increases the relative abundance of Clostridium in mice.

    “SDR reduces the relative abundance of bacteria from the genus Bacteroides, while increasing the relative abundance of bacteria from the genus Clostridium.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    § Introduction

    A recent report in the New England Journal of Medicine describes structural brain abnormalities in autistic children that began during prenatal brain development.

    “A recent report in the New England Journal of Medicine describes structural brain abnormalities in autistic children that began during prenatal brain development,116”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Stoner R, Chow ML, Boyle MP, et al. : Patches of disorganization in the neocortex of children with autism. N Engl J Med 2014;370:1209–1219 [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisenone given
    § Introduction

    Administration of Bacteroides fragilis to MIA mice corrects excessive gut permeability, alters gut microbial composition, and ameliorates defects in communication and stereotypic, anxiety-like, and sensorimotor behaviors.

    “Administration of a single probiotic, Bacteroides fragilis, corrects excessive gut permeability, alters gut microbial composition, and ameliorates defects in communication and stereotypic, anxiety-like, and sensorimotor behaviors in the MIA model.”
    Quote in the paperSubstantial claim

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    Interpretationcitation
    § Introduction

    Probiotic supplements may improve depression or anxiety through three interrelated mechanisms: decreased intestinal permeability with reduced LPS absorption and inflammatory cytokines, downregulation of the HPA axis in response to stressors, and direct effects on neurotransmission.

    “Studies in mice and rats support the following interrelated mechanisms: (1) decrease in intestinal permeability resulting in reduced absorption of LPS and reduced production of inflammatory cytokines, (2) downregulation of the HPA axis in responding to stressors, and (3) direct effects on neurotransmission.”
    Quote in the paperSubstantial claim

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    Premisecitation
    § Introduction

    Intrinsic primary afferent neurons are cellular targets of neuroactive bacteria and transmit microbial messages to the brain via the vagus nerve.

    “Intrinsic primary afferent neurons (IPANs) are cellular targets of neuroactive bacteria and transmit microbial messages to the brain via the vagus nerve.135,136”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [135] Bravo JA, Forsythe P, Chew MV, et al. : Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA 2011;108:16050–16055 [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Certain gut bacteria synthesize neurotransmitters: Lactobacillus species produce acetylcholine and GABA; Bifidobacterium species produce GABA; Escherichia produce norepinephrine, serotonin, and dopamine; Streptococcus and Enterococcus produce serotonin; and Bacillus species produce norepinephrine and dopamine.

    “Lactobacillus species produce acetylcholine and gamma-amino butyrate (GABA); Bifidobacterium species produce GABA; Escherichia produce norepinephrine, serotonin and dopamine; Streptococcus and Enterococcus produce serotonin; and Bacillus species produce norepinephrine and dopamine.17”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation
    § Introduction

    In volunteers with stress-related irritable bowel symptoms, a probiotic combination of L. acidophilus Rosell-52 and B. longum Rosell-175 reduced abdominal pain and nausea but had no effect on psychological symptoms or sleep disturbances.

    “another probiotic combination, L. acidophilus Rosell-52 and B. longum Rosell-175, reduced abdominal pain and nausea but had no effect on psychological symptoms or sleep disturbances.133”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [133] Diop L, Guillou S, Durand H: Probiotic food supplement reduces stress-induced gastrointestinal symptoms in volunteers: a double-blind, placebo-controlled, randomized trial. Nutr Res 2008;28:1–5 [DOI] [PubMed] [Google Scholar] source

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    § Introduction

    D-lactic acid and ammonia are the most studied encephalotoxic metabolites.

    “The most studied are D-lactic acid60 and ammonia.61”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [60] Thurn JR, Pierpont GL, Ludvigsen CW, Eckfeldt JH: D-lactate encephalopathy. Am J Med 1985;79:717–721 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [61] Qureshi MO, Khokhar N, Shafqat F: Ammonia levels and the severity of hepatic encephalopathy. J Coll Physicians Surg Pak 2014;24:160–163 [PubMed] [Google Scholar]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    In healthy French adults, 30 days of Lactobacillus helveticus R0052 and B. longum R0175 significantly reduced psychological distress on HSCL-90, HADS, and CCL, and reduced urinary free cortisol.

    “The probiotic combination significantly reduced psychological distress as measured by the HSCL-90 scale (with significant reductions in global severity index, somatization, depression, and anger-hostility scores), the HADS (significant reductions in the global severity index and anxiety), and the CCL (significant increase in problem solving). There was a significant reduction in UFC.126”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [126] Messaoudi M, Lalonde R, Violle N, et al. : Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 2011;105:755–764 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    SDR increases circulating levels of inflammatory cytokines, especially IL-6, which are significantly correlated with stressor-induced changes in microbiome composition.

    “It also increases circulating levels of inflammatory cytokines, IL-6 in particular, which are significantly correlated with stressor-induced changes in microbiome composition.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [121] Bailey MT, Dowd SE, Galley JD, et al. : Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun 2011;25:397–407 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    In adults with chronic fatigue syndrome, 8 weeks of the same probiotic preparation had no effect on depression but significantly improved Beck Anxiety Inventory scores compared with placebo.

    “There was no effect on depression, but those receiving the probiotic demonstrated significant improvement on the Beck Anxiety Inventory compared with the placebo group.131”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [131] Rao AV, Bested AC, Beauline TM, et al. : A randomized double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog 2009;1:6. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    Pretreatment of mice with antibiotics alters the changes in community structure and attenuates the cytokine response after SDR.

    “Pretreatment of mice with antibiotics alters the changes in community structure and attenuates the cytokine response after SDR.121”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [121] Bailey MT, Dowd SE, Galley JD, et al. : Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun 2011;25:397–407 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

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

    Premisecitation
    § Introduction

    In 15 patients with chronic fatigue syndrome, 4 weeks of a probiotic mixture improved memory and concentration but not fatigue or physical activity.

    “Patients reported improvement in memory and concentration but not in fatigue or physical activity.132”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [132] Sullivan A, Nord CE, Evengård B: Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J 2009;8:4. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    Gut bacteria and their secretions influence neuronal excitation in the enteric nervous system, regulating gut motility and sensory afferent signaling to the brain.

    “Gut bacteria and their secretions influence neuronal excitation in the enteric nervous system (ENS), regulating both gut motility and sensory afferent signaling to the brain.134”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [134] Forsythe P, Kunze WA, Bienenstock J: On communication between gut microbes and the brain. Curr Opin Gastroenterol 2012;28:557–562 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    In mice, manipulation of the gut microbiome can alter behavior and CNS levels of brain-derived neurotrophic factor without vagal involvement.

    “Both behavior and CNS levels of brain-derived neurotrophic factor can be altered in mice by manipulation of the gut microbiome without vagal involvement.12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Bercik P, Park AJ, Sinclair D, et al. : The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil 2011;23:1132–1139 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Conclusion

    Several mechanisms, none mutually exclusive, may enable commensal gut bacteria to influence function or dysfunction in the CNS: stimulation of host immune responses leading to systemic cytokine activation; synthesis of absorbable neuroactive metabolites, including neurotransmitters; and alterations in neuronal circuitry by direct microbial effects on the ENS, with CNS transmission through vagal и

    “Several mechanisms, none mutually exclusive, may enable commensal gut bacteria to influence function or dysfunction in the CNS: (1) stimulation of host immune responses leading to diverse patterns of systemic cytokine activation; (2) synthesis of absorbable neuroactive metabolites, including neurotransmitters; and (3) alterations in neuronal circuitry by direct microbial effects on the ENS, with”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    The microbiota of the effluent from the ileum is simpler and less stable than colonic fecal microflora and is dominated by different bacterial phyla.

    “the microbiota of the effluent from the ileum is both simpler and less stable than colonic fecal microflora and is dominated by different bacterial phyla.145”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [145] Booijink CC, El-Aidy S, Rajilić-Stojanović M, et al. : High temporal and inter-individual variation detected in the human ileal microbiota. Environ Microbiol 2010;12:3213–3227 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    A diet high in animal protein and fat favors abundance of Bacteroides, while a vegetarian diet or one high in monosaccharides favors abundance of Prevotella species.

    “A diet high in animal protein and fat favors abundance of Bacteroides. A vegetarian diet or one high in monosaccharides favors abundance of Prevotella species.148”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [148] Wu GD, Chen J, Hoffmann C, et al. : Linking long-term dietary patterns with gut microbial enterotypes. Science 2011;334:105–108 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    Extreme dietary changes, such as a ketogenic diet, produce immediate profound changes in the human gut microbiome, while less dramatic interventions produce mild to moderate changes that vary from person to person and tend to be less than inter-individual variability.

    “Extreme dietary changes, such as adoption of a ketogenic diet, produce immediate profound changes in the human gut microbiome. Less dramatic interventions produce mild to moderate changes that vary from person to person and tend to be less than inter-individual variability.155”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [155] Albenberg LG, Wu GD: Diet and the intestinal microbiome: associations, functions, and implications for health and disease. Gastroenterology 2014;146:1564–1572 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

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

    Premisecitation
    § Introduction

    A normal microbiome increases nutrient bioavailability; germ-free mice should be fed a diet of higher nutrient quantity and diversity than conventional mice to maintain their health.

    “A normal microbiome increases nutrient bioavailability. In order to maintain their health, GF mice should be fed a diet of higher nutrient quantity and diversity than conventional mice.156”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [156] Jeffery IB, O'Toole PW: Diet-microbiota interactions and their implications for healthy living. Nutrients 2013;5:234–252 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    Higher plasma levels of trimethylamine-N-oxide (TMAO) conferred an increased risk of major cardiovascular events during a 3-year follow-up; plasma TMAO is the product of gut microbial metabolism of dietary choline to trimethylamine, followed by hepatic oxidation to TMAO.

    “higher plasma levels of the vascular toxin trimethylamine-N-oxide (TMAO) conferred an increased risk of major cardiovascular events during a 3-year follow-up.157 They also demonstrated that plasma TMAO is the product of gut microbial metabolism of dietary choline to trimethylamine (TMA), followed by hepatic oxidation of TMA to TMAO.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [157] Tang WH, Wang Z, Levison BS, et al. : Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013;368:1575–1584 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

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

    Premisecitation
    § Introduction

    Most human adult gut microbiota belong to the genera Faecalibacterium, Bacteroides, Roseburia, Ruminococcus, Eubacterium, Coprabacillus, and Bifidobacterium.

    “Most belong to the genera Faecalibacterium, Bacteroides, Roseburia, Ruminococcus, Eubacterium, Coprabacillus, and Bifidobacterium.147”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [147] Tap J, Mondot S, Levenez F, Pelletier E, et al. : Towards the human intestinal microbiota phylogenetic core. Environ Microbiol 2009;11:2574–2584 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Conclusion

    Gut bacteria may influence mood, pain sensitivity and normal brain development.

    “They may influence mood, pain sensitivity and normal brain development.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    Most studies indicate that both health and decreased adiposity are associated with increased diversity of the gut microflora; dietary restriction increases diversity, while dietary excess tends to reduce it.

    “Most studies indicate that both health and decreased adiposity are associated with increased diversity of the gut microflora. Dietary restriction increases diversity; dietary excess tends to reduce it.154”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [154] Joyce SA, Gahan CG: The gut microbiota and the metabolic health of the host. Curr Opin Gastroenterol 2014;30:120–127 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    Human gut microbial composition differs substantially among individuals and depends on age, genetic background, physiological state, microbial interactions, environmental factors, and diet.

    “Human studies have unveiled substantial differences in the gut microbial composition among individuals139–141 that depend on age, genetic background, physiological state, microbial interactions, environmental factors, and diet.142–144”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [139] Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P: Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA 2010;107:14691–14696 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [140] Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA: Diversity of the human intestinal microbial flora. Science 2005;308:1635–1638 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [141] Turnbaugh PJ, Quince C, Faith JJ, McHardy AC, Yatsunenko T, Niazi F, Affourtit J, Egholm M, Henrissat B, Knight R, Gordon JI: Organismal, genetic, and transcriptional variation in the deeply sequenced gut microbiomes of identical twins. Proc Natl Acad Sci USA 2010;107:7503–7508 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [142] Turnbaugh PJ, Gordon JI: The core gut microbiome, energy balance, and obesity. J Physiol 2009;587:4153–4158 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [143] Rajilic-Stojanovic M, Heilig HG, Molenaar D, Kajander K, Surakka A, Smidt H, de Vos WM: Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults. Environ Microbiol 2009;11:1736–1751 [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [144] Dethlefsen L, Eckburg PB, Bik EM, Relman DA: Assembly of the human intestinal microbiota. Trends Ecol Evol 2006;21:517–523 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation
    § Conclusion

    Prebiotics, probiotics, and fermented foods such as yogurt may influence the impact of the gut microbiome on the CNS and have shown significant effects on brain function in a number of experimental trials and clinical studies.

    “Prebiotics, probiotics, and fermented foods such as yogurt may influence the impact of the gut microbiome on the CNS and have shown significant effects on brain function in a number of experimental trials and clinical studies.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Administering a probiotic does more than just introduce a new bacterial species, which may or may not establish a niche in the community.

  • May combine two claims.

    Premisecitation
    § Introduction

    Colonic bacteria have been found in biofilms formed around food particles, organizing gut microbes into distinct communities that behave differently from planktonic counterparts; bacteria in food-associated biofilms produce unique signaling molecules and may represent a new dimension in the relationship between food, microbes, and human health.

    “Colonic bacteria have been found in biofilms formed around food particles. These organize gut microbes into distinct communities that behave differently from their planktonic counterparts. Bacteria living in food-associated biofilms produce unique signaling molecules and may represent a new dimension in the relationship between food, microbes, and human health.160”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [160] Van Wey AS, Cookson AL, Roy NC, et al. : Bacterial biofilms associated with food particles in the human large bowel. Mol Nutr Food Res 2011;55:969–978 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

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

    Premisecitation
    § Introduction

    High consumption of oligosaccharides favors growth of Bifidobacteria, which is the dominant genus of breast-fed infants, who receive most of their carbohydrate as breast milk oligosaccharides.

    “High consumption of oligosaccharides favors growth of Bifidobacteria, which is the dominant genus of breast-fed infants, who receive most of their carbohydrate in the form of breast milk oligosaccharides.149”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [149] Walker WA: Initial intestinal colonization in the human infant and immune homeostasis. Ann Nutr Metab 2013;63Suppl 2:8–15 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given
    § Conclusion

    Gut bacteria influence reactivity of the HPA axis and the induction and maintenance of nREM sleep.

    “Gut bacteria influence reactivity of the HPA axis and the induction and maintenance of nREM sleep.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    Polyphenols are bioactive non-nutrient plant compounds whose bioavailability and physiologic effects depend on transformation by gut microbiota; polyphenols alter microbial growth patterns; and polyphenol composition may be more important than macronutrient composition for determining growth effects on gut microbes.

    “Polyphenols are bioactive non-nutrient plant compounds whose bioavailability and physiologic effects greatly depend on their transformation by components of the gut microbiota. Polyphenols, in turn, alter microbial growth patterns. The polyphenol composition of an individual's diet may be more important than macronutrient composition for determining growth effects on gut microbes.159”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [159] Laparra JM, Sanz Y: Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol Res 2010;61:219–225 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Introduction

    Administering a probiotic may change gut community structure in unexpected ways, and these changes may or may not alter community function.

    “It may change community structure in unexpected ways, and these changes may or may not alter community function.138”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [138] Sanders ME: Impact of probiotics on colonizing microbiota of the gut. J Clin Gastroenterol 2011;45Suppl:S115–S119 [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • Rests on an assumption: Administering a probiotic does more than just introduce a new bacterial species, which may or may not establish a niche in the community.
62 of 62

  • The paper relies on this without support.

    The effect of diet change on the microbiome is not unidirectional.

    “The effect of diet change on the microbiome is not likely to be unidirectional.”

  • The paper relies on this without support.

    Gut microbes exist in interconnected and highly structured living communities.

    “gut microbes exist in a series of interconnected and highly structured living communities.”

  • The paper relies on this without support.

    There is almost no published research describing actual diet-microbiome-CNS effects in humans.

    “There is almost no published research that describes actual diet— >microbiome— >CNS effects in humans, just allusions to such an effect.”

  • The paper relies on this without support.

    Administering a probiotic does more than just introduce a new bacterial species, which may or may not establish a niche in the community.

    “Administering a probiotic does more than just introduce a new bacterial species, which may or may not be able to establish a niche in the community.”
4 of 4

Claims other papers make about this one

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  • Chemical signaling from the gut microbiota to the central nervous system affects memory, motivation, mood and stress reactivity.

    “Recently uncovered chemical signaling from the gut microbiota to the central nervous system, affecting memory, motivation, mood and stress reactivity, raises questions about the long-term cognitive effects of disturbed microbiota composition at a sensitive time in brain development25, 26.”

    From The relation between cesarean birth and child cognitive development (2017) · cites this paper as [26]

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Authors
Galland, L.
Affiliations
Foundation for Integrated Medicine
Corresponding author
Galland, Leo
Venue
Journal of Medicinal Food
Publisher
SAGE Publications
Published
2014-12
Volume
17
Issue
12
Pages
1261-1272
ISSN
  • 1096-620X (ISSN-L)
  • 1557-7600
DOI
10.1089/jmf.2014.7000
PMC
PMC4259177
OpenAlex
W1551543102
Semantic Scholar
671fe304ecf646655c4902ded3bf3bee6d4e1723
Cited by
648
References
161
Citations by year
2026: 17 · 2025: 49 · 2024: 61 · 2023: 92 · 2022: 87 · 2021: 81 · 2020: 83 · 2019: 49 · 2018: 48 · 2017: 38 · 2016: 31 · 2015: 12
FWCI
2.54
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Medicinal Food (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords
gut microbiota, gut-brain axis, lipopolysaccharide, innate immune activation, bacterial dysbiosis, small intestinal bacterial overgrowth, intestinal permeability, neuroinflammation, D-lactate, ammonia, short-chain fatty acids, neurotoxicity, bacterial metabolites, gastrointestinal hormones, neurotransmitters, enteric nervous system, vagus nerve, hypothalamic-pituitary-adrenal axis, sleep, stress reactivity, memory, mood, cognition, alcoholism, chronic fatigue syndrome, fibromyalgia, restless legs syndrome, multiple sclerosis, celiac disease, probiotics, prebiotics, diet
MeSH terms
Brain, Diet, Humans, Hypothalamo-Hypophyseal System, Immunity, Innate, Neurosecretory Systems, Pituitary-Adrenal System, Gastrointestinal Tract, Adaptive Immunity, Microbiota

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