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Cited by 254Gut microbiota and healthGastrointestinal motility and disordersTryptophan and brain disorders

Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review

Open access
Chinna Meyyappan, Arthi, Forth, Evan, Wallace, Caroline J. K., Milev, Roumen·2020·BMC Psychiatry
DOI 10.1186/s12888-020-02654-5PMC PMC7294648

Published version of a preprint

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Abstract

Background: The Gut-Brain-Axis is a bidirectional signaling pathway between the gastrointestinal (GI) tract and the brain. The hundreds of trillions of microorganisms populating the gastrointestinal tract are thought to modulate this connection, and have far reaching effects on the immune system, central and autonomic nervous systems, and GI functioning. These interactions Diagnostic and statistical manual of mental disorders have also been linked to various psychiatric illnesses such as depression, anxiety, substance abuse, autism spectrum disorder, and eating disorders. It is hypothesized that techniques aimed at strengthening and repopulating the gut microbiome, such as Fecal Microbiota Transplant (FMT), may be useful in the prevention and treatment of psychiatric illnesses. Methods: A systematic search of five databases was conducted using key terms related to FMT and psychiatric illnesses. All results were then evaluated based on specific eligibility criteria. Results: Twenty-one studies met the eligibility criteria and were analysed for reported changes in mood and behavioural measures indicative of psychiatric wellbeing. The studies included were either entirely clinical ( n = 8), preclinical with human donors ( n = 9), or entirely preclinical ( n = 11). All studies found a decrease in depressive and anxiety-like symptoms and behaviours resulting from the transplantation of healthy microbiota. The inverse was also found, with the transmission of depressive and anxiety-like symptoms and behaviours resulting from the transplantation of microbiota from psychiatrically ill donors to healthy recipients. Conclusion: There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT. Further research with larger sample sizes and stronger scientific design is warranted in order to fully determine the efficacy and safety of this potential treatment. Registered on PROSPERO, IRD: CRD42019126795.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review synthesizes preclinical and clinical evidence that fecal microbiota transplant (FMT) can both alleviate and transmit psychiatric symptoms via the gut-brain axis. It reports consistent short-term improvements in depression and anxiety symptoms after healthy-donor FMT, but notes transient effects and major limitations in study design.

Key findings

  • The review reports 28 included studies: 11 entirely preclinical, 9 preclinical with human donors, and 8 clinical; the abstract states 21 studies met eligibility, an internal inconsistency in the paper.
  • All included studies found a decrease in depressive and anxiety-like symptoms/behaviours after transplantation of healthy microbiota, and the inverse was found when microbiota from psychiatrically ill donors was transplanted into healthy recipients.
  • In clinical studies, all eight assessed psychiatric symptoms; all found significant short-term improvement in depression symptoms, but long-term effects were less consistent, with three studies finding return to baseline at week 12, week 20, and month 6, while Xie et al. found persistent decrease up to 17 months.
  • Of four clinical studies assessing anxiety, three found significant improvement; Mizuno et al. found improvement that was not significant, and Mazzawi et al. found improvement insignificant by week 20.

Methods

  • Systematic search of five databases (MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science) using terms related to mood, anxiety, mania, stress, phobia, microbiota transfer, and fecal transplant; November 2019 search yielded 285 studies after duplicates, and an April 2020 update yielded 7 new studies after full-text screening.
  • Eligibility required peer-reviewed English articles with preclinical or clinical samples assessed for changes in psychiatric illness symptoms after endogenous microbe transfer via any route; PRISMA guidelines were followed, and two authors independently screened titles/abstracts and full texts, with disagreements resolved by a third author.
  • Study quality was assessed with the Cochrane Risk of Bias Tool across six domains; non-double-blind randomized studies were included if methodology was comprehensive after review by three authors.

Limitations

  • Stated: there is no agreed definition of a “healthy microbiome”; clinical studies had small sample sizes and lacked large-scale double-blind randomized controlled trials; most clinical studies assessed psychiatric symptoms in individuals with IBS rather than exclusively psychiatric disorders, so improvement may be secondary to GI symptom improvement.
  • Stated: preclinical human-donor studies mostly used only male donors or mice, some donors took medications including antidepressants, and variability in antibiotics for germ-free mice and FMT administration protocols limits translation and comparability.
  • Evident: the abstract reports 21 eligible studies while the Results section reports 28 included studies; allocation concealment was not assessed because no studies concealed treatment allocation, and blinding failures were rated as high bias.

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

Integrity signals

Registry

Crossref · 10.1186/s12888-020-02654-5

Cites

75 of 75 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 65 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    FMT from CUMS mice to germ-free mice resulted in increased anxiety and depression-like behaviour in three studies.

    “When investigating the effects of FMT from CUMS mice to germ free mice, three studies found that the FMT resulted in increased anxiety and depression-like behaviour [21–23].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [21] Li N, et al. Fecal microbiota transplantation from chronic unpredictable mild stress mice donors affects anxiety-like and depression-like behavior in recipient mice via the gut microbiota-inflammation-brain axis. Stress. 2019;22(5):592–602 https://doi.org/10.1080/10253890.2019.1617267. source

      Not checked in the free run.

    • cites [22] Lv W, et al. The gut microbiome modulates the changes in liver metabolism and in inflammatory processes in the brain of chronic unpredictable mild stress rats. Oxidative Med Cell Longev. 2019;2019:1–14 https://doi.org/10.1155/2019/7902874. source

      Not checked in the free run.

    • cites [23] Siopi E, et al. Changes in gut microbiota by chronic stress impair the efficacy of fluoxetine. Cell Rep. 2020;30(11):3682–3690.e6 https://doi.org/10.1016/j.celrep.2020.02.099. source

      Not checked in the free run.

  • Findingcitation

    FMT from NLPR3 knockout mice resulted in a decrease in anxiety and depressive-like behaviours in recipient mice.

    “It was found that FMT from NLPR3 knockout mice resulted in a decrease in anxiety and depressive-like behaviours in the recipient mice [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Zhang Y, et al. Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2. Microbiome. 2019;7(1):116 https://doi.org/10.1186/s40168-019-0733-3. source

      Not checked in the free run.

  • Findingown data

    The symptoms most frequently studied were Irritable Bowel Syndrome, chronic stress, and depressive-like symptoms.

    “The symptoms most frequently studied were that of Irritable Bowel Syndrome (IBS), chronic stress, and depressive-like symptoms.”
    Quote in the paperNot a substantial claim
  • Findingcitation

    FMT from patients with depression to germ-free mice can result in depression-like behaviour in recipient mice.

    “These four studies all support that FMT from patients with depression to GF mice can result in depression-like behaviour in the recipient mice.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [34] Kelly JR, et al. Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res. 2016;82:109–18 https://doi.org/10.1016/j.jpsychires.2016.07.019. source

      Not checked in the free run.

    • cites [35] Zheng P, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol Psychiatry. 2016;21(6):786–96 https://doi.org/10.1038/mp.2016.44. source

      Not checked in the free run.

    • cites [36] Huang C, et al. Proteomic analysis of olfactory bulb suggests CACNA1E as a promoter of CREB signaling in microbiota-induced depression. J Proteome. 2019b;194:132–47 https://doi.org/10.1016/j.jprot.2018.11.023. source

      Not checked in the free run.

    • cites [37] Liu S, Guo R, Liu F, Yuan Q, Yu Y, Ren F. Gut microbiota regulates depression-like behavior in rats through the neuroendocrine-immune-mitochondrial pathway. Neuropsychiatr Dis Treat. 2020;16:859–69 https://doi.org/10.2147/NDT.S243551. source

      Not checked in the free run.

  • Findingcitation

    FMT from alcohol-treated mice to healthy control mice resulted in depressive behaviour in recipient mice.

    “This transplantation resulted in depressive behaviour in the recipient mice. This behaviour was evaluated using the forced swim and tail suspension tests [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Xiao H, et al. Gut microbiota modulates alcohol withdrawal-induced anxiety in mice. Toxicol Lett. 2018;287:23–30 https://doi.org/10.1016/j.toxlet.2018.01.021. source

      Not checked in the free run.

  • May combine two claims. 35
  • Classified as probably not a substantial claim. 27
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    Of the included studies, eleven examined exclusively animal samples, nine were preclinical subjects with transplanted microbiota from human donors, and eight examined exclusively human samples.

    “Of these, eleven studies examined exclusively animal samples, nine studies were preclinical subjects with transplanted microbiota from human donors, and eight studies examined exclusively human samples.”
    • Also stated in: § Results · plain
      “The studies included were either entirely clinical (n = 8), preclinical with human donors (n = 9), or entirely preclinical (n = 11).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    SL/vulnerable rats displayed increased depressive and anxiety-like behaviours, whereas LL/resilient rats did not.

    “SL/vulnerable rats displayed increased depressive and anxiety-like behaviours, whereas LL/resilient rats did not.”
    Quote in the paperSubstantial claim

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

    Findingown data

    Four of the preclinical studies failed to report rodent sample size.

    “Four of the preclinical studies failed to report rodent sample size.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Transplants from anhedonia-susceptible rats aggravated pain and depression-like symptoms, and those from anhedonia-resilient rats improved pain and depression-like symptoms.

    “It was found that transplants from anhedonia susceptible rats aggravated pain and depression-like symptoms, and those receiving from anhedonia resilient microbiotas had improved pain and depression-like symptoms.”
    Quote in the paperSubstantial claim

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

    Findingown data

    This review contains 28 studies evaluating the effect of fecal microbiota transplants on various psychiatric and physical symptoms.

    “This review contains 28 studies evaluating the effect of fecal microbiota transplants on various psychiatric and physical symptoms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the eleven preclinical studies, the primary indications investigated were chronic stress (n = 6), alcoholism (n = 2), chronic neuropathic pain (n = 2), and depression (n = 1).

    “In the eleven preclinical studies included in this review (Table 2), the primary indications investigated were chronic stress (n = 6), alcoholism (n = 2), chronic neuropathic pain (n = 2), and depression (n = 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    FMT from SHC to CSC mice was mildly stress protective, resulting in decreased anxiety and depression-like symptoms in recipient mice.

    “It was found that these transplants were mildly stress protective, resulting in decreased anxiety and depression-like symptoms in the recipient mice [25].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Langgartner D, et al. The role of the intestinal microbiome in chronic psychosocial stress-induced pathologies in male mice. Front Behav Neurosci. 2018;12:252 https://doi.org/10.3389/fnbeh.2018.00252. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The average sample size was n = 23 for entirely preclinical studies, n = 78 for preclinical studies with human donors, and n = 19 for clinical studies.

    “The average sample size was n = 23 for entirely preclinical studies, and n = 78 for preclinical studies with human donors, and n = 19 for clinical studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    FMT from alcohol-treated mice to germ-free mice resulted in depressive-like behaviours, but treating donors with nicotinamide riboside before transplantation stopped the transmission.

    “Similar results were found after FMT from alcohol treated mice, but treating the donors with nicotinamide riboside before transplantation stopped the transmission of depressive-like behaviours [30].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Jiang Y, Liu Y, Gao M, Xue M, Wang Z, Liang H. Nicotinamide riboside alleviates alcohol-induced depression-like behaviours in C57BL/6J mice by altering the intestinal microbiota associated with microglial activation and BDNF expression. Food Funct. 2020;11(1):378–91 https://doi.org/10.1039/C9FO01780A. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Rats receiving FMT from SL/vulnerable rats displayed depressive-like behaviours in the forced swim test, while LL/resilient recipients were not significantly different from control.

    “It was found that rats receiving FMT from the SL/vulnerable group displayed depressive-like behaviours when asses with the forced swim test while the LL/resilient group was not significantly different than control [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Pearson-Leary J, et al. The gut microbiome regulates the increases in depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats. Mol Psychiatry. 2019;25:1–12 https://doi.org/10.1038/s41380-019-0380-x. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Mizuno et al. found improvement in anxiety scores but it was not significant.

    “Although Mizuno et al. found improvement in the anxiety scores as well, it was not significant [44].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Mizuno S, et al. Bifidobacterium-rich fecal donor may be a positive predictor for successful fecal microbiota transplantation in patients with irritable bowel syndrome. Digestion. 2017;96(1):29–38 https://doi.org/10.1159/000471919. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Long-term effects on depression were less consistent, with three studies finding a return to baseline at week 12, week 20, and month 6 respectively.

    “The long-term effects were less consistent, with three studies finding a return to baseline at week 12, week 20, and month 6 respectively [44–46].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [44] Mizuno S, et al. Bifidobacterium-rich fecal donor may be a positive predictor for successful fecal microbiota transplantation in patients with irritable bowel syndrome. Digestion. 2017;96(1):29–38 https://doi.org/10.1159/000471919. source

      Not checked in the free run.

    • cites [45] Huang HL, et al. Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota. J Dig Dis. 2019c;20(8):401–8 https://doi.org/10.1111/1751-2980.12756. source

      Not checked in the free run.

    • cites [46] Mazzawi T, et al. The kinetics of gut microbial community composition in patients with irritable bowel syndrome following fecal microbiota transplantation. PLoS ONE. 2018;13(11):e0194904 https://doi.org/10.1371/journal.pone.0194904. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Fatigue improved up to 6 months after FMT and waned from 6 to 12 months.

    “Johnsen et al. also found a similar effect on fatigue, with improvement up to 6 months after FMT and a waning effect from 6 to 12 months [49].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Johnsen PH, Hilpüsch F, Valle PC, Goll R. The effect of fecal microbiota transplantation on IBS related quality of life and fatigue in moderate to severe non-constipated irritable bowel: secondary endpoints of a double blind, randomized, placebo-controlled trial. EBioMedicine. 2020;51:102562 https://doi.org/10.1016/j.ebiom.2019.11.023. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Transplants from anxious IBS donors resulted in more anxiety-like behaviour in recipient mice, but this was not the same for transplants from IBS donors without anxiety.

    “In their study, it was found that transplants from anxious IBS donors resulted in more anxiety-like behaviour in recipient mice. This was not the same for transplants from IBS donors without anxiety [43].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] De Palma G, et al. Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice. Sci Transl Med. 2017;9(379):eaaf6397 https://doi.org/10.1126/scitranslmed.aaf6397. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    A significant decrease in EPQ-N-12 neuroticism scores was seen at week 3, but this returned to baseline by week 20.

    “A significant decrease in EPQ-N-12 scores was seen at week 3, but this returned to baseline by week 20 [46].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Mazzawi T, et al. The kinetics of gut microbial community composition in patients with irritable bowel syndrome following fecal microbiota transplantation. PLoS ONE. 2018;13(11):e0194904 https://doi.org/10.1371/journal.pone.0194904. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    All eight clinical studies assessed psychiatric symptoms; six assessed depressive symptoms, four assessed anxiety symptoms, one assessed neuroticism, two assessed quality of life in relation to IBS, and one assessed fatigue.

    “All eight clinical studies assessed for psychiatric symptoms – six studies assessed depressive symptoms, four assessed anxiety symptoms, one assessed neuroticism, two assessed quality of life in relation to IBS, and one assessed fatigue.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    IBS-QOL scores showed significant improvement during the first 3 to 6 months and returned to baseline after 6 to 12 months.

    “Scores on this questionnaire followed a similar pattern as the assessments above, with a significant improvement being observed during the first 3 to 6 months and returning to baseline after 6 to12 months [45, 49].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [45] Huang HL, et al. Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota. J Dig Dis. 2019c;20(8):401–8 https://doi.org/10.1111/1751-2980.12756. source

      Not checked in the free run.

    • cites [49] Johnsen PH, Hilpüsch F, Valle PC, Goll R. The effect of fecal microbiota transplantation on IBS related quality of life and fatigue in moderate to severe non-constipated irritable bowel: secondary endpoints of a double blind, randomized, placebo-controlled trial. EBioMedicine. 2020;51:102562 https://doi.org/10.1016/j.ebiom.2019.11.023. source

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    Transference of psychiatric symptoms to GF mice was observed from mouse models of depression, anxiety, chronic stress, and alcoholism, and from humans with depression.

    “This was supported in multiple studies, with observed transference of symptoms from mouse models of depression, anxiety, chronic stress and alcoholism, and from humans with depression, to GF mice.”
    Quote in the paperSubstantial claim

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

    Findingnone given

    Some recipients received multiple FMTs, while others received only one, and the justification for choosing donors varied.

    “For instance, some recipients received multiple FMTs, while others received only one and the justification for choosing donors varied.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In disease- or stress-states, these pathways may become compromised, resulting in intestinal dysbiosis, changes in mood, behavior, and cognition, and altered inflammatory levels.

    “In disease- or stress-states these pathways may become compromised resulting in intestinal dysbiosis, changes in mood, behavior, and cognition, and altered inflammatory levels [1].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13(10):701–12 https://doi.org/10.1038/nrn3346. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The interaction of the gut with environmental risk factors of psychiatric illnesses suggests that interventions targeting the gut microbiome could prevent and treat psychiatric symptoms.

    “The interaction of the gut with the environmental risk factors of psychiatric illnesses, such as diet and early life stress, suggests that interventions targeting the gut microbiome could prevent and treat psychiatric symptoms [8].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Dash S, Clarke G, Berk M, Jacka FN. The gut microbiome and diet in psychiatry: focus on depression. Curr Opin Psychiatry. 2015;28(1):1 https://doi.org/10.1097/YCO.0000000000000117. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Gut bacteria play a vital role in regulating important aspects of brain development and function, along with other host physiology.

    “Studies have since shown that gut bacteria play a vital role in regulating important aspects of brain development and function, along with other host physiology [5, 7].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [5] O’Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006;7(7):688–93 https://doi.org/10.1038/sj.embor.7400731. source

      Not checked in the free run.

    • cites [7] Stilling RM, Dinan TG, Cryan JF. Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis. Genes Brain Behav. 2014;13(1):69–86 https://doi.org/10.1111/gbb.12109. source

      Not checked in the free run.

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

    Study design and conductown data

    Allocation concealment was not assessed because no studies concealed treatment allocation from subjects or participants.

    “Allocation concealment was not assessed since no studies concealed treatment allocation from subjects or participants.”
    Quote in the paperNot a substantial claim

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

    Study design and conductcitation

    This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

    “This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Fig. 1, [20]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097 https://doi.org/10.1371/journal.pmed.1000097. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The increased immobility and decreased centre time suggest transfer of depression symptoms from FSL rats to others, and the FRL result provides evidence against transference of resiliency from FRL rats.

    “The former suggests the transfer of depression symptoms from FSL rats to others, and the latter provides evidence against the transference of resiliency from FRL rats.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Some investigations have shown neurochemical changes as a result of gut microbiome dysfunction, such as altered BDNF levels, reduced serotonin receptor expression, reduced synaptic plasticity gene expression, and increased striatal monoamine turnover.

    “Some investigations have shown neurochemical changes as a result of gut microbiome dysfunction, such as altered levels of brain-derived neurotropic factor (BDNF), reduced serotonin receptor expression, reduced synaptic plasticity gene expression, and increased striatal monoamine turnover [10–12].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [10] Sudo N, et al. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. J Physiol. 2004;558(Pt 1):263–75 https://doi.org/10.1113/jphysiol.2004.063388. source

      Not checked in the free run.

    • cites [11] Heijtz RD, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A. 2011;108(7):3047–52 https://doi.org/10.1073/pnas.1010529108. source

      Not checked in the free run.

    • cites [12] Neufeld KM, Kang N, Bienenstock J, Foster JA. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil. 2011;23(3):255–e119 https://doi.org/10.1111/j.1365-2982.2010.01620.x. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Studies that did not follow the double-blind, randomized controlled model were included if they had a comprehensive methodology after thorough analysis by three authors.

    “As there is limited research on this topic, studies that did not follow the double-blind, randomized controlled model, were included if they had a comprehensive methodology after thorough analysis by three of the authors (A.C.M., C.W., and R.M.).”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    All included studies were analyzed according to the Cochrane Risk of Bias Tool domains by two authors.

    “All included studies were analyzed according to these domains by A.C.M and C.W.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Overall, the included studies presented with low levels of potential bias except where blinding of either the participant or study team was not performed, where bias was assessed as high.

    “Overall, the included studies presented with low levels of potential bias save for cases where blinding of either the participant or study team was not performed. For these cases, bias was assessed as high.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Two authors independently assessed titles and abstracts and completed full-text review, with disagreements resolved by a third author.

    “Two authors (A.C.M and C.W) independently assessed the titles and abstracts of records retrieved from the systematic search according to the identified inclusion and exclusion criteria and completed the full-text review. Any disagreements were resolved by a third author (R.M).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The gut microbiome may both contribute to the development of psychiatric disorders and be a viable target for treatment for these disorders.

    “This provides support for the concept that the gut microbiome may both contribute to the development of psychiatric disorders and be a viable target for treatment for these disorders.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT.

    “There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    FMT can confer certain traits of the donor's psychiatric illnesses to the recipient mouse, and transplants from healthy donors may be able to alleviate some psychiatric symptoms.

    “These studies all show that FMT can confer certain traits of the donor’s psychiatric illnesses to the recipient mouse, and that transplants from healthy donors may be able to alleviate some psychiatric symptom.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Anorexia is closely tied to mood and anxiety disorders; the likelihood of someone with anorexia having a comorbid mood disorder is 2.4 times and an anxiety disorder is 1.9 times higher than the general public.

    “Anorexia is also closely tied to mood and anxiety disorders, with the likelihood of someone with anorexia having a comorbid mood or anxiety disorder being 2.4 and 1.9 times higher respectively than the general public [41].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Hudson JI, Hiripi E, Pope HG, Kessler RC. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry. 2007;61(3):348–58 https://doi.org/10.1016/j.biopsych.2006.03.040. source

      Not checked in the free run.

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

    Premisecitation

    Alcoholism is highly comorbid with mood and anxiety disorders; someone with alcoholism is 3.6 times more likely to have a mood disorder and 2.6 times more likely to have an anxiety disorder.

    “Alcoholism is highly comorbid with mood and anxiety disorders, with someone with alcoholism being 3.6 and 2.6 times more likely to have a mood or anxiety disorder respectively [38].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Petrakis IL, Gonzalez G, Rosenheck R, Krystal JH. Comorbidity of alcoholism and psychiatric disorders. Alcohol Res Health. 2002;26(2):81–9.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    Given FMT effects can last up to 6 months, it may be easier to adhere to than a daily medication or a weekly psychotherapy appointment.

    “However, given FMT effects can last up to 6 months, it may be easier to adhere to than a daily medication or a weekly psychotherapy appointment.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The safety of FMT has not been sufficiently understood.

    “Additionally, the safety of FMT has also not been sufficiently understood and its associated stigma is still unknown.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    An estimated 90% of the body's serotonin is produced by enterochromaffin (EC) cells in the digestive tract.

    “An estimated 90% of the body’s serotonin is produced by enterochromaffin (EC) cells in the digestive tract [51].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diab Obes. 2013;20(1):14–21 https://doi.org/10.1097/MED.0b013e32835bc703. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    These mechanisms may provide insight into the use of FMT as a potential treatment for psychiatric symptoms, such as mood and anxiety.

    “These mechanisms may provide insight into the use of FMT as a potential treatment for psychiatric symptoms, such as mood and anxiety.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The repopulation of the gut microbiome with healthy bacteria through FMT may have positive neurological, immune, and metabolic effects which in turn may influence the trajectory of the psychiatric indication.

    “The repopulation of the gut microbiome with healthy bacteria through FMT may have positive neurological, immune, and metabolic effects which in turn may influence the trajectory of the psychiatric indication.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    The associated stigma of FMT is still unknown.

    “Additionally, the safety of FMT has also not been sufficiently understood and its associated stigma is still unknown.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    FMT is relatively expensive and a labor-intensive alternative to other psychiatric treatments.

    “Although costs are comparable to antidepressants, it is still relatively expensive and a labor-intensive alternative to other psychiatric treatments.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The studies included in this review were of good quality.

    “Although the studies included in this review were of good quality and contributed to a greater understanding of FMT in the context of mental health and illness, there are considerable limitations.”
    Quote in the paperNot a substantial claim

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

    Interpretationcitation

    Assuming one transplant is sufficient for therapeutic benefits lasting up to 6 months, the cost of FMT treatment may be comparable to that of brand-name antidepressants.

    “Assuming one transplant is sufficient for therapeutic benefits lasting up to 6 months, the cost of treatment may be comparable to that of brand-name antidepressants, however not much is known about the costs of FMT (Eisenberg Centre at Oregon Health & Sciences University, 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Eisenberg Centre at Oregon Health & Sciences University, 2007

      Not checked in the free run.

    • The authors state this as an assumption: One transplant is sufficient for therapeutic benefits lasting up to 6 months.

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

    Premisecitation

    SCFAs produced by the gut microbiome have anti-inflammatory properties and can work to regulate the immune response.

    “The SCFAs produced by the gut microbiome have anti-inflammatory properties and can work to regulate the immune response [54].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] van de Wouw M, et al. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations. J Physiol. 2018;596(20):4923–44 https://doi.org/10.1113/JP276431. source

      Not checked in the free run.

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

    Premisecitation

    SSRIs are the most prescribed treatment for depression.

    “Serotonin transmission has long been known to be altered in depression, with selective serotonin reuptake inhibitors (SSRIs) being the most prescribed treatment for depression [50].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Treviño LA, Ruble MW, Treviño K, Weinstein LM, Gresky DP. Antidepressant medication prescribing practices for treatment of major depressive disorder. Psychiatr Serv. 2017;68(2):199–202 https://doi.org/10.1176/appi.ps.201600087. source

      Not checked in the free run.

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

    Premisecitation

    Serotonin transmission is altered in depression.

    “Serotonin transmission has long been known to be altered in depression, with selective serotonin reuptake inhibitors (SSRIs) being the most prescribed treatment for depression [50].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Treviño LA, Ruble MW, Treviño K, Weinstein LM, Gresky DP. Antidepressant medication prescribing practices for treatment of major depressive disorder. Psychiatr Serv. 2017;68(2):199–202 https://doi.org/10.1176/appi.ps.201600087. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Interpretationreasoning

    The transient benefit of FMT (around 3-6 months) is a limitation for FMT in clinical practice.

    “which, if used as a treatment for psychiatric disorders, is a limitation for FMT in clinical practice.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Without a consensus on a standard procedure for conducting this research, it is difficult to compare results between studies.

    “Without a consensus on a standard procedure for conducting this research, it is difficult to compare results between studies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Finding treatment that works for all patients with psychiatric disorders is not achievable.

    “Given the huge heterogeneity of psychiatric disorders, finding treatment that works for all patients is not achievable, especially given the range of factors that influence the disorder and treatment response.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Progress in research in treatment of psychiatric disorders has been challenging due to high individual variability, comorbidity, genetic and environmental influences.

    “With high individual variability in symptomatology and prognosis, high levels of comorbidity with other disorders, genetic and environmental influences, progress in research in treatment of psychiatric disorders has been challenging.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Some studies included donors that were taking various medications, including antidepressants.

    “Some of these studies also included donors that were taking various medications, including antidepressants, which may have affected the results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Given the adaptable nature of the gut microbiome, it may be a good representation of the individual's history and could explain differences in risk of illness, disease course, and response to treatment.

    “Additionally, given the adaptable nature of the gut microbiome, it may be a good representation of the individual’s history and could explain differences in risk of illness, disease course, and response to treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The administration of antibiotics to create GF recipient mice and the variability in FMT administration protocol make the findings difficult to translate.

    “Additionally, the administration of antibiotics to create GF recipient mice and the variability in FMT administration protocol make the findings difficult to translate.”
    Quote in the paperNot a substantial claim
54 of 54

  • The paper relies on this without support.

    Many people with Major Depressive Disorder or anxiety disorders deny pharmacological treatment due to side effects or stigma-related reasons, or are treatment-resistant and unable to find an effective way to improve their symptoms.

    “While there are pharmacological treatments available for both disorders, many people deny treatment due to side effects or stigma-related reasons or are treatment-resistant and unable to find an effective way to improve their symptoms.”

  • The paper relies on this without support.

    There are few studies on FMT in humans as a treatment method in the context of psychiatric disorders.

    “However, as this is a relatively novel area of research, there are few studies on FMT in humans as a treatment method in the context of psychiatric disorders.”

  • The paper relies on this without support.

    The gut-brain axis is a bidirectional signaling pathway between the gastrointestinal tract and the brain.

    “The Gut-Brain-Axis is a bidirectional signaling pathway between the gastrointestinal (GI) tract and the brain.”
    “The GBA consists of bidirectional biochemical and neural signalling between the gastrointestinal (GI) tract and the brain.”

  • The authors state this as an assumption.

    One transplant is sufficient for therapeutic benefits lasting up to 6 months.

    “Assuming one transplant is sufficient for therapeutic benefits lasting up to 6 months”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • There is strong evidence for the possibility of targeting the gut-brain axis with fecal microbiota transplantation to mitigate depression- and anxiety-like symptoms.

    “Based on mentioned above clinical trials, but also the latest systematic review by Chinna Meyyappan et al. [85], there is strong evidence for the possibility of targeting the gut-brain axis with FMT to mitigate depression-and anxiety-like symptoms.”

    From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [85]

  • Reported studies on the therapeutic benefits of fecal microbial transfer in patient populations for other psychiatric conditions have been reviewed with mixed results.

    “Reported studies about therapeutic benefits of fecal microbial transfer in patient populations for other psychiatric conditions have recently been reviewed with mixed results (Chinna Meyyappan et al., 2020).”

    From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as Chinna Meyyappan et al., 2020

  • The evaluation of the potential therapeutic benefit of fecal microbial transplants in brain disorders, mimicking such effects previously reported in animal models has shown inconsistent and time limited success, with the exception of the study in ASD discussed earlier.

    “The evaluation of the potential therapeutic benefit of fecal microbial transplants in brain disorders, mimicking such effects previously reported in animal models has shown inconsistent and time limited success [123], with the exception of the study in ASD discussed earlier.”

    From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [123]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Abstract study total does not match its categories

    Major

    The three categories contain 8, 9, and 11 studies, totaling 28 rather than the reported 21. The Results section also states that the review contains 28 studies.

    Reported 21 · recomputed 28

  • Mizuno study is counted as both significant and nonsignificant for anxiety

    Minor

    Reference [44] is included among studies said to show significant anxiety improvement, then identified as Mizuno et al., whose improvement is said not to be significant.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Petrakis IL, Gonzalez G, Rosenheck R, Krystal JH. Comorbidity of alcoholism and psychiatric disorders. Alcohol Res Health. 2002;26(2):81–9.

Cited by

Sorted by citations

Related

Authors
Chinna Meyyappan, A., Forth, E., Wallace, C. J. K., & Milev, R.
Affiliations
Queen's University (CA)
ORCID
Venue
BMC Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2020-06-15
Volume
20
Issue
1
Pages
299-299
ISSN
1471-244X (ISSN-L)
DOI
10.1186/s12888-020-02654-5
PMC
PMC7294648
OpenAlex
W3035496405
Semantic Scholar
a86c26c27f357bd731df3414f7607e645cfa15c8
Cited by
254
References
75
Citations by year
2026: 31 · 2025: 53 · 2024: 41 · 2023: 37 · 2022: 44 · 2021: 43 · 2020: 5
FWCI
3.09
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Psychiatry (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Canadian Institutes of Health Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
fecal microbiota transplantation, gut-brain axis, mental illness, depression, anxiety, gut microbiota, autism spectrum disorder, eating disorders, substance abuse
MeSH terms
Autism Spectrum Disorder, Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Anxiety, Humans, Microbiota

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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