CoChat
Sign Up
Cited by 595Gut microbiota and healthAutism Spectrum Disorder ResearchGastrointestinal motility and disorders

Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder

Open access
Vuong, Helen E., Hsiao, Elaine Y.·2017·Biological Psychiatry
DOI 10.1016/j.biopsych.2016.08.024PMC PMC5285286
Open this paper in CoChat — free account

Abstract

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that affects one in 45 children in the United States, with a similarly striking prevalence in countries around the world. However, mechanisms underlying its etiology and manifestations remain poorly understood. Although ASD is diagnosed based on the presence and severity of impaired social communication and repetitive behavior, immune dysregulation and gastrointestinal issues are common comorbidities. The microbiome is an integral part of human physiology; recent studies show that changes in the gut microbiota can modulate gastrointestinal physiology, immune function, and even behavior. Links between particular bacteria from the indigenous gut microbiota and phenotypes relevant to ASD raise the important question of whether microbial dysbiosis plays a role in the development or presentation of ASD symptoms. Here we review reports of microbial dysbiosis in ASD. We further discuss potential effects of the microbiota on ASD-associated symptoms, drawing on signaling mechanisms for reciprocal interactions among the microbiota, immunity, gut function, and behavior. In addition, we discuss recent findings supporting a role for the microbiome as an interface between environmental and genetic risk factors that are associated with ASD. These studies highlight the integration of pathways across multiple body systems that together can impact brain and behavior and suggest that changes in the microbiome may contribute to symptoms of neurodevelopmental disease.

Integrity signals

Registry

Crossref · 10.1016/j.biopsych.2016.08.024

Cites

152 of 152 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 69 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Transfer of gut microbiota from control mice into offspring of high fat diet-fed mothers corrects impairments in sociability and social novelty.

    “Remarkably, transfer of the gut microbiota from control mice into offspring of high fat diet-fed mothers completely corrected the impairments in sociability and social novelty seen in the mice, demonstrating a key role for the gut microbiome in regulating mouse social behavior.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Buffington, 2016, Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring, Cell source

      Not checked in the free run.

  • Premisecitation

    Postnatal colonization of germ-free mice with wildtype mouse gut microbiota at weaning corrects some social impairments.

    “Moreover, some of the social impairments are corrected by postnatal colonization of germ-free mice with a wildtype mouse gut microbiota at weaning, pointing to the ability to reverse abnormalities in social interactions (26).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Clarke, 2013, The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner, Mol Psychiatry source

      Not checked in the free run.

  • Premisecitation

    Germ-free rats exhibit reduced social investigation of an unfamiliar partner.

    “This is similarly seen in germ-free rats, which exhibit reduced social investigation of an unfamiliar partner (24).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Crumeyrolle-Arias, 2014, Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats, Psychoneuroendocrinology source

      Not checked in the free run.

  • Premisecitation

    ASD is associated with a higher prevalence of gastrointestinal disorders and disturbances compared to controls.

    “Parallel studies reveal greater prevalence of gastrointestinal disorders and disturbances in ASD populations compared to controls (19, 20).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] Adams, 2011, Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity, BMC Gastroenterol source

      Not checked in the free run.

    • cites [20] Williams, 2012, Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances, mBio source

      Not checked in the free run.

  • Premisecitation

    Alterations in gut microbiota are observed in ASD individuals compared to neurotypical controls.

    “Alterations in the gut microbiota are observed in ASD individuals compared to neurotypical controls (Table 1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Table 1

      Not checked in the free run.

  • May combine two claims. 18
  • Classified as probably not a substantial claim. 5

  • May combine two claims.

    Premisecitation

    ASD patients show increased microglia and astroglia activation in the cerebellum and cerebral cortex, and increased proinflammatory cytokines in cerebrospinal fluid and cortical regions.

    “Postmortem brains of ASD patients show increased microglia and astroglia activation in the cerebellum and cerebral cortex, along with increased levels of proinflammatory cytokines in the cerebrospinal fluid and cortical regions of the brain (16).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Vargas, 2005, Neuroglial activation and neuroinflammation in the brain of patients with autism, Ann Neurol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Deficient gut epithelium integrity and increased intestinal permeability are reported in ASD.

    “Deficient integrity of the gut epithelium and increased intestinal permeability are also reported (21).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Emanuele, 2010, Low-grade endotoxemia in patients with severe autism, Neurosci Lett source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High fat diet-induced maternal obesity alters offspring gut microbiome and causes social behavioral deficits linked to altered mesolimbic reward signaling.

    “A recent study by Buffington et al. showed that high fat diet induced-maternal obesity alters the offspring gut microbiome and causes social behavioral deficits that are linked to altered signaling in the mesolimbic reward system (29).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Buffington, 2016, Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring, Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a mouse model of maternal immune activation, mice develop core behavioral features of ASD, neuropathologies, and co-morbid GI and immunological symptoms.

    “In a mouse model of maternal immune activation, a principal environmental risk factor for autism, mice develop core behavioral features of ASD (impaired social communication and stereotyped behaviors), as well as several neuropathologies and co-morbid gastrointestinal and immunological symptoms relevant to the human disorder (30–32).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [30] Coiro, 2015, Impaired synaptic development in a maternal immune activation mouse model of neurodevelopmental disorders, Brain Behav Immun source

      Not checked in the free run.

    • cites [31] Shi, 2003, Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring, J Neurosci source

      Not checked in the free run.

    • cites [32] Hsiao, 2013, Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders, Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Germ-free mice exhibit decreased sociability and reduced social preference for unfamiliar versus familiar mice.

    “Two independent studies demonstrate that germ-free mice exhibit decreased sociability or propensity to interact with a novel mouse versus non-social object, and reduced social preference to interact with an unfamiliar versus familiar mouse (22, 23).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [22] Desbonnet, 2014, Microbiota is essential for social development in the mouse, Mol Psychiatry source

      Not checked in the free run.

    • cites [23] Arentsen, 2015, Host microbiota modulates development of social preference in mice, Microb Ecol Health Dis

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Early life treatment with Bacteroides fragilis ameliorates deficits in ultrasonic vocalizations and reduces stereotypic burying behavior in maternal immune activation mice.

    “Altering the postnatal gut microbiota by early life treatment with the human gut bacterium Bacteroides fragilis sufficiently ameliorated deficits in the frequency and quality of adult ultrasonic vocalizations and reduced stereotypic burying behavior exhibited by the ASD-like mice.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [30] Coiro, 2015, Impaired synaptic development in a maternal immune activation mouse model of neurodevelopmental disorders, Brain Behav Immun source

      Not checked in the free run.

    • cites [31] Shi, 2003, Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring, J Neurosci source

      Not checked in the free run.

    • cites [32] Hsiao, 2013, Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders, Cell source

      Not checked in the free run.

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

    Premisenone given

    Many studies report dysbiosis of the gut microbiota in ASD individuals.

    “Many studies report dysbiosis of the gut microbiota in ASD individuals.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    ASD-associated genes encode immune system components, and mutations in those genes are linked with ASD phenotype.

    “Moreover, there are ASD-associated genes that encode for features of the immune system, and mutations in those genes are linked with ASD phenotype, including loss of structural and functional connectivity in brain regions important for socio-communicative function (17, 18).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17] Estes, 2015, Immune mediators in the brain and peripheral tissues in autism spectrum disorder, Nat Rev Neurosci source

      Not checked in the free run.

    • cites [18] Hsiao, 2013, Immune dysregulation in autism spectrum disorder, Int Rev Neurobiol source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    The developing embryo is largely devoid of microbial colonization, and mammals inherit their initial microbiome through the birthing process.

    “The developing embryo is largely devoid of microbial colonization, and a preponderance of evidence suggests that mammals inherit their initial microbiome through the birthing process.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Gut microbes influence intestinal barrier integrity, epithelial cell regeneration, mucus production and GI motility.

    “Gut microbes influence various aspects of gut physiology, including intestinal barrier integrity, epithelial cell regeneration, mucus production and gastrointestinal motility (59).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Burger-van Paassen, 2009, The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: Implications for epithelial protection, Biochem J source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    The microbiota is well positioned at the intersection between genes and environment, as its composition and function depend on genetic background and are shaped by environmental factors.

    “The microbiota is well positioned at the intersection between genes and environment, as its composition and function are dependent on genetic background and critically shaped by environmental factors, including age, infection, diet and xenobiotics.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    GI problems are common in individuals with autism and could potentiate behavioral issues.

    “Although the precise incidence varies from study to study, there is a general consensus that GI problems are common in individuals with autism (57) and that they could potentiate behavioral issues (57).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] McElhanon, 2014, Gastrointestinal symptoms in autism spectrum disorder: A meta-analysis, Pediatrics source

      Not checked in the free run.

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

    Premisecitation

    Several genetic factors increase ASD risk, including SNPs, CNVs and de novo mutations in genes involved in synaptic transmission and neuronal activity.

    “Several genetic factors increase ASD risk, including short nucleotide polymorphisms (SNPs), copy number variants (CNVs) and de novo mutations in genes involved in synaptic transmission and neuronal activity (82–84).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [82] Micheau, 2014, Impaired hippocampus-dependent spatial flexibility and sociability represent autism-like phenotypes in GluK2 mice, Hippocampus source

      Not checked in the free run.

    • cites [83] Aller, 2015, Increased dosage of high-affinity kainate receptor gene grik4 alters synaptic transmission and reproduces autism spectrum disorders features, J Neurosci source

      Not checked in the free run.

    • cites [84] Rendall, 2016, Learning delays in a mouse model of autism spectrum disorder, Behav Brain Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The microbiota conveys lasting effects of infection to the host and can regulate epigenetic modification of the host genome.

    “The microbiota also conveys lasting effects of infection to the host (89) and can regulate epigenetic modification of the host genome (90, 91).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [89] Buffie, 2012, Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis, Infect Immun source

      Not checked in the free run.

    • cites [90] Kumar, 2014, Gut microbiota as an epigenetic regulator: Pilot study based on whole-genome methylation analysis, mBio

      Not checked in the free run.

    • cites [91] Cortese, 2016, Epigenome-microbiome crosstalk: A potential new paradigm influencing neonatal susceptibility to disease, Epigenetics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Some studies report C-section is associated with elevated risk for ASD in offspring, though one reported no link.

    “Consistent with this, some studies report that C-section is associated with elevated risk for ASD in the offspring (108, 109), though one reported no link between C-section and ASD symptoms (110).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [108] Curran, 2015, Association between obstetric mode of delivery and autism spectrum disorder: A population-based sibling design study, JAMA Psychiatry source

      Not checked in the free run.

    • cites [109] Curran, 2015, Research review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: A systematic review and meta-analysis, J Child Psychol Psychiatry source

      Not checked in the free run.

    • cites [110] Curran, 2016, Obstetrical mode of delivery and childhood behavior and psychological development in a British cohort, J Autism Dev Disord source

      Not checked in the free run.

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

    Premisenone given

    Idiopathic ASD is thought to result from a combination of several genetic and environmental factors that each contributes a fraction of disease risk.

    “Idiopathic ASD is thought to be a result of a combination of several genetic and environmental factors that each contributes a fraction of disease risk.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Vancomycin treatment in ASD children reported some improvements in ASD behaviors, which waned when antibiotic treatment was discontinued.

    “Interestingly, a small clinical study of vancomycin treatment in ASD children reported some improvements in ASD behaviors, which waned when antibiotic treatment was discontinued (50), suggesting that the microbiome may contribute actively to the severity of behavioral abnormalities in ASD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Sandler, 2000, Short-term benefit from oral vancomycin treatment of regressive-onset autism, J Child Neurol source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    This microbial dysbiosis is correlated with lasting behavioral abnormalities, neuropathologies, immune dysfunction and deficient gastrointestinal integrity.

    “This microbial dysbiosis is correlated with lasting behavioral abnormalities, neuropathologies, immune dysfunction and deficient gastrointestinal integrity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    No defined microbial signature has been identified for ASD, though many studies report microbiome differences within independent cohorts of ASD and controls.

    “That is, no defined microbial signature has been identified for ASD, though many studies report microbiome differences within independent cohorts of ASD and controls (Table 1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Table 1

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    B. fragilis and Clostridial consortium correct symptoms of intestinal disease and multiple sclerosis in animal models.

    “By this mechanism, B. fragilis and Clostridial consortium sufficiently correct symptoms of intestinal disease and multiple sclerosis in animal models (74, 75) and continue to be tested for clinical translation into patient populations.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [74] Round, 2011, The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota, Science source

      Not checked in the free run.

    • cites [75] Ochoa-Reparaz, 2010, Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression, J Immunol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Animal models demonstrate microbiome changes in response to maternal stress are passed onto offspring at birth, setting in motion microbial dysbiosis that persists into adulthood.

    “Animal models demonstrate that microbiome changes in response to maternal stress are passed onto offspring at birth, setting in motion microbial dysbiosis that persists into adulthood (105–107).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [105] Golubeva, 2015, Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood, Psychoneuroendocrinology source

      Not checked in the free run.

    • cites [106] Jasarevic, 2015, Alterations in the vaginal microbiome by maternal stress are associated with metabolic reprogramming of the offspring gut and brain, Endocrinology source

      Not checked in the free run.

    • cites [107] De Palma, 2015, Microbiota and host determinants of behavioural phenotype in maternally separated mice, Nat Commun source

      Not checked in the free run.

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

    Premisenone given

    The gut microbiota exhibits important bidirectional interactions with the immune system.

    “The gut microbiota exhibits important bidirectional interactions with the immune system.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Emerging studies suggest the microbiota is an important regulator of gastrointestinal physiology, immune function and behavior.

    “Emerging studies suggest the microbiota is an important regulator of gastrointestinal physiology, immune function and behavior (Figure 1).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Figure 1

      Not checked in the free run.

23 of 23

  • The paper relies on this without support.

    The gut microbiota is an integral part of human physiology.

    “The microbiome is an integral part of human physiology; recent studies show that changes in the gut microbiota can modulate gastrointestinal physiology, immune function and even behavior.”

  • The paper relies on this without support.

    The gut microbiota plays an important role in regulating normal host physiology, metabolism, nutrition, and brain function.

    “The microbiota plays an important role in regulating normal host physiology, metabolism, nutrition, and brain function.”
2 of 2

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?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Vuong, H. E., & Hsiao, E. Y.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Hsiao, Elaine Y.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2017-03
Volume
81
Issue
5
Pages
411-423
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2016.08.024
PMC
PMC5285286
OpenAlex
W2515537885
Cited by
595
References
152
Citations by year
2026: 45 · 2025: 45 · 2024: 53 · 2023: 59 · 2022: 82 · 2021: 89 · 2020: 92 · 2019: 55 · 2018: 49 · 2017: 25 · 2016: 1
FWCI
3.91
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Alfred P. Sloan Foundation
  • National Institutes of Health (DP5OD017924)
  • National Institute of Mental Health (F31MH090749)
  • National Institute of General Medical Sciences (K12GM106996)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
autism spectrum disorder, gut microbiota, dysbiosis, immune dysregulation, gastrointestinal symptoms, neurodevelopmental disorders, microbiota-immune interactions, environmental risk factors, genetic risk factors, neurobehavioral symptoms
MeSH terms
Autism Spectrum Disorder, Gastrointestinal Microbiome, Adolescent, Adult, Animals, Behavior, Animal, Brain, Child, Child, Preschool, Disease Models, Animal, Humans, Risk Factors, Gastrointestinal Tract, Mice, Endophenotypes

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 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

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

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review