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Cited by 159Autism Spectrum Disorder ResearchChild Nutrition and Feeding IssuesGastrointestinal motility and disorders

Gastrointestinal Issues and Autism Spectrum Disorder

Open access
Madra, Moneek, Ringel, Roey, Margolis, Kara Gross·2020·Child and Adolescent Psychiatric Clinics of North America
DOI 10.1016/j.chc.2020.02.005PMC PMC8608248
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Abstract

Gastrointestinal disorders are one of the most common medical conditions that are comorbid with autism spectrum disorders. These comorbidities can cause greater severity in autism spectrum disorder symptoms, other associated clinical manifestations, and lower quality of life if left untreated. Clinicians need to understand how these gastrointestinal issues present and apply effective therapies. Effective treatment of gastrointestinal problems in autism spectrum disorder may result in marked improvements in autism spectrum disorder behavioral outcomes. This article discusses the gastrointestinal disorders commonly associated with autism spectrum disorders, how they present, and studied risk factors.

AI snapshot

Written from the paper’s full text.

TL;DR

Gastrointestinal disorders are common and morbidity-causing in autism spectrum disorder (ASD), with constipation, diarrhea, and abdominal pain most frequently reported, and they often co-occur with sleep, psychiatric, and behavioral problems. Diagnosis is difficult because children with ASD may not localize or verbalize GI distress, and microbiota-based treatments remain promising but not established.

Key findings

  • GI symptom prevalence in children with ASD varies from 9–91%; a comprehensive meta-analysis found children with ASD were more than four-fold more likely to develop GI problems than those without ASD, with constipation, diarrhea, and abdominal pain reported most commonly. Constipation odds increase with greater social impairment and less verbal ability.
  • Children with ASD are up to five times more likely to develop feeding problems such as food selectivity, food refusal, and poor oral intake; food selectivity often favors carbohydrates and processed foods, tends to be more severe than in age-matched children, and lasts past childhood. In one study, 60% of ASD patients displayed pica at some stage.
  • Sleep abnormalities affect 80% of children with ASD, and psychiatric disorders occur in up to 70%, with anxiety most common. GI problems are associated with more irritability, social withdrawal, and hyperactivity; unexplained irritable behavior was found in 43% of ASD children with esophagitis.
  • A 17-question parent-report GI screen had sensitivity 86%, specificity 43%, and positive predictive value 67%, and detected new GI diagnoses in over 20% of patients. An open-label fecal microbiota transplant study in 18 patients showed improved GI and behavioral outcomes persisting eight weeks and at two-year follow-up; a probiotic pilot found parent-reported GI improvement but no significant quality-of-life improvement.

Methods

  • Narrative review/chapter, not original research; it synthesizes human and animal literature on GI issues in ASD.
  • Covers prevalence and types of GI disorders, clinical comorbidities, risk factors, diagnosis, and treatment, citing meta-analyses, a consensus report, screening validation, clinical trials, and mouse models.
  • No systematic search strategy, inclusion criteria, or primary data collection are described.

Limitations

  • The paper states that microbiome studies in ASD have been small with extremely variable results; gluten- and/or casein-free diet benefits have not been confirmed in double-blind placebo-controlled trials; one gluten immune-reactivity finding has not been replicated; and a recent study found dietary patterns were not associated with GI symptoms in children with ASD.
  • The paper states the FMT study was small (18 patients) and open-label, and probiotic trials were small and/or lacked a true control group, so larger double-blind placebo-controlled trials are needed.
  • Evident from the text: as a narrative review, it does not systematically appraise evidence quality, and it relies partly on animal/preclinical findings that may not directly generalize to children with ASD.

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

Integrity signals

Registry

Crossref · 10.1016/j.chc.2020.02.005

Cites

81 of 81 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 118 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    GI disorders are often overlooked in children with ASD.

    “Despite their prevalence, GI disorders are often overlooked 3.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] McElhanon, 2014, Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis, Pediatrics source

      Not checked in the free run.

  • Premisenone given

    Children with ASD are up to five times more likely to develop feeding problems than neurodevelopmentally normal children.

    “Since that time, it has been found that children with ASD are up to five times more likely to develop feeding problems, such as food selectivity, food refusal, and poor oral intake, than neurodevelopmentally normal children.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    The prevalence of GI symptoms in children with ASD varies from 9% to 91%.

    “In fact, the prevalence of GI symptoms in children with ASD varies from 9-91% 14.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Buie, 2010, Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report, Pediatrics source

      Not checked in the free run.

  • Premisecitation

    Food selectivity in children with ASD is often manifested as a preference for carbohydrates and processed foods.

    “Food selectivity in this population is often manifested as a preference for carbohydrates and processed foods 89.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [8] Ahearn, 2001, An assessment of food acceptance in children with autism or pervasive developmental disorder-not otherwise specified, J Autism Dev Disord source

      Not checked in the free run.

    • cites [9] Bandini, 2017, Changes in food selectivity in children with autism spectrum disorder, J Autism Dev Disord source

      Not checked in the free run.

  • Premisecitation

    Children with ASD are more than four-fold more likely to develop GI problems than those without ASD.

    “The most comprehensive meta-analysis to date revealed that children with ASD were more than four-fold more likely to develop GI problems than those without ASD”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] McElhanon, 2014, Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis, Pediatrics source

      Not checked in the free run.

  • May combine two claims. 34
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Premisecitation

    Constipation is the primary GI comorbidity with ASD, and the odds of constipation increase with greater social impairment and less verbal ability.

    “Other studies have reported constipation as the primary GI comorbidity with ASD, where the odds of constipation increase with greater social impairment and less verbal ability 15.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Gorrindo, 2012, Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors, Autism Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Food selectivity in ASD tends to be more severe than in age-matched children and lasts past childhood.

    “This behavior tends to be more severe than in age-matched children and lasts past childhood 1011.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Cermak, 2010, Food selectivity and sensory sensitivity in children with autism spectrum disorders, J Am Diet Assoc source

      Not checked in the free run.

    • cites [11] Twachtman-Reilly, 2008, Addressing feeding disorders in children on the autism spectrum in school-based settings: physiological and behavioral issues, Lang Speech Hear Serv Sch source

      Not checked in the free run.

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

    Premisecitation

    Sleep abnormalities affect 80% of children with ASD and range from reduced sleep duration to parasomnias.

    “Sleep abnormalities affect 80% of children with ASD and range from reduced sleep duration to parasomnias 2627.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [26] Rossignol, 2011, Melatonin in autism spectrum disorders: a systematic review and meta-analysis, Dev Med Child Neurol source

      Not checked in the free run.

    • cites [27] Mannion, 2012, An investigation of comorbid psychological disorders, sleep problems, gastrointestinal symptoms and epilepsy in children and adolescents with autism spectrum disorder, Res Autism Spectr Disord source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Psychiatric comorbidities in ASD do not differ between males and females and often persist from childhood into adolescence.

    “These comorbidities do not differ between males and females and often persist from childhood into adolescence 34,35.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34] Hofvander, 2009, Psychiatric and psychosocial problems in adults with normal-intelligence autism spectrum disorders, BMC Psychiatry source

      Not checked in the free run.

    • cites [35] Simonoff, 2013, The persistence and stability of psychiatric problems in adolescents with autism spectrum disorders, J Child Psychol Psychiatry source

      Not checked in the free run.

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

    Premisecitation

    A multi-expert consensus report outlined best practices for evaluating and treating GI disorders in children with ASD, focusing on abdominal pain, constipation, chronic diarrhea and GERD as the most common causes.

    “In 2010, a multi-expert panel published a consensus report on GI disorders in ASD that outlined the best practices for evaluating and treating GI disorders in children with ASD. These guidelines focused on abdominal pain, constipation, chronic diarrhea and gastroesophageal reflux disease (GERD), which were again noted as the most common causes of GI problems in ASD 14.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Buie, 2010, Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report, Pediatrics source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Predominant GI conditions in ASD, including constipation and abdominal pain, cause abdominal discomfort which could be an impediment to good sleep hygiene.

    “The predominant GI conditions seen in ASD, including constipation and abdominal pain, cause abdominal discomfort which could be an impediment to good sleep hygiene 14.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Buie, 2010, Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report, Pediatrics source

      Not checked in the free run.

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

    Premisecitation

    Psychiatric disorders occur in up to 70% of patients with ASD.

    “Psychiatric disorders occur in up to 70% of patients with ASD.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Simonoff, 2008, Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample, J Am Acad Child Adolesc Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    L. reuteri restored social impairments in multiple ASD mouse models, and this process is mediated directly through the nervous system and not via changes in the gut microbiome.

    “Recently, L. reuteri restored social impairments in multiple ASD mouse models and novel insights into this mechanism have revealed that this process is mediated directly through the nervous system and not via changes in the gut microbiome 60.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Sgritta, 2019, Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder, Neuron source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    One report shows that children with ASD have increased immune reactivity to gluten and this immune response is enhanced when GI symptoms are present, but this study has not been replicated.

    “There is also one report showing that children with ASD have increased immune reactivity to gluten and this immune response is enhanced when GI symptoms are present, but this study, like the aforementioned one, has not been replicated 53.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Lau, 2013, Markers of celiac disease and gluten sensitivity in children with autism, PLoS One source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In one study, administration of a high fat diet during gestation in mice resulted in pups with gut microbiota dysbiosis, reduced sociability, fewer oxytocin neurons in the hypothalamus and reduced synaptic plasticity in the ventral tegmental area.

    “In one of these studies, administration of a HFD during gestation in mice resulted, in the pups, in a gut microbiota dysbiosis, reduced sociability, fewer oxytocin neurons in the hypothalamus and reduced synaptic plasticity in the ventral tegmental area (VTA) of offspring.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] 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

    Studies of intestinal microbiota in children with ASD have been small and results extremely variable.

    “the studies have been small and the results have been extremely variable 51.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Vuong, 2017, Emerging roles for the gut microbiome in autism spectrum disorder, Biol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Animal research has shown that a maternal high fat diet is associated with gut microbiota dysbiosis, resulting in changes in central neurobiology and abnormal social behaviors, linking maternal diet and dysbiosis to neurodevelopmental disorders.

    “In line with these clinical studies, animal research has shown that a maternal high fat diet (HFD) is associated with gut microbiota dysbiosis, that results in changes in central neurobiology and abnormal social behaviors, linking the maternal diet and dysbiosis to neurodevelopmental disorders 59.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] Buffington, 2016, Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring, Cell source

      Not checked in the free run.

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

    Premisecitation

    A recent study showed that dietary patterns were not associated with the GI symptoms seen in children with ASD.

    “a recent study showed that dietary patterns were not associated with the GI symptoms seen in children with ASD 54.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Ferguson, 2019, Lack of associations between dietary intake and gastrointestinal symptoms in autism spectrum disorder, Front Psychiatry source

      Not checked in the free run.

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

    Premisenone given

    Diet is an environmental factor that may affect ASD symptomatology.

    “Diet is an environmental factor that may affect ASD symptomatology.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    Impaired carbohydrate metabolism may be a reason why some children with ASD respond poorly to gluten ingestion.

    “This could thus be a reason why some kids with ASD respond poorly to gluten ingestion.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Mice and/or non-human primates exposed to maternal immune activation through maternal infection with poly(I:C) or maternal influenza infection have offspring that develop abnormal social behaviors, deficits in immune profiles and anxiety-like phenotypes.

    “Similarly, mice and/or non-human primates that are exposed to maternal immune activation (MIA) through maternal infection with the viral mimetic, polyinosinic: polycitidylic acid (poly (I:C)), or maternal influenza infection, have offspring that develop abnormal social behaviors 646566, deficits in their immune profiles and anxiety-like phenotypes 67.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [64] Shi, 2009, Activation of the maternal immune system alters cerebellar development in the offspring, Brain Behav Immun source

      Not checked in the free run.

    • cites [65] Bauman, 2014, Activation of the maternal immune system during pregnancy alters behavioral development of rhesus monkey offspring, Biol Psychiatry source

      Not checked in the free run.

    • cites [66] Shi, 2003, Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring, J Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Basic experiments have demonstrated a possible role for the gut microbiome in the generation of ASD-like phenotypes and possible novel treatment modalities.

    “These basic experiments have demonstrated a possible role for the gut microbiome in the generation of ASD-like phenotypes and, excitingly, possible novel treatment modalities.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    A lack of Lactobacillus reuteri was implicated as one cause of the dysbiosis seen in this diet-induced phenotype and treatment with Lactobacillus reuteri resulted in improvements in the CNS and social deficits.

    “A lack of Lactobacillus reuteri was implicated as one cause of the dysbiosis seen in this diet-induced phenotype and treatment with Lactobacillus reuteri resulted in improvements in the CNS and social deficits 59.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] 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

    Anecdotal reports suggest an improvement in GI and/or behavioral symptoms in individuals on gluten- and/or casein-free diets, but these findings have not been confirmed in double-blind placebo-controlled trials.

    “Though anecdotal reports suggest an improvement in GI and/or behavioral symptoms in individuals on gluten- and/or casein-free diets, these findings have not been confirmed in double-blind placebo-controlled trials 45.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Hyman, 2016, The gluten-free/casein-free diet: a double-blind challenge trial in children with autism, J Autism Dev Disord source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Maternal immune activation has been shown to cause increased gut permeability and gut dysbiosis.

    “Interestingly, MIA has also been shown to cause increased gut permeability and gut dysbiosis 6869.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [68] Hsiao, 2013, Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders, Cell source

      Not checked in the free run.

    • cites [69] Malkova, 2012, Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism, Brain Behav Immun source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Changing the microbiome may correct brain and behavioral defects induced by dysbiosis, suggesting that intestinal microbiota may be an underlying cause of CNS dysfunction in ASD and that its manipulation could be a novel therapeutic option.

    “Interestingly, studies have also shown that changing the microbiome may correct the brain and behavioral defects induced by a dysbiosis, suggesting that the intestinal microbiota may be an underlying cause of the CNS dysfunction in ASD and also that its manipulation could be a novel therapeutic option 5960.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [59] Buffington, 2016, Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring, Cell source

      Not checked in the free run.

    • cites [60] Sgritta, 2019, Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder, Neuron source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    The FMT study had a small patient sample (18 patients) and was open-label, leaving outcomes open to the effects of placebo.

    “Though the results of this study are exciting, the patient sample was small (18 patients) and the trial was open-label, leaving outcomes open to the effects of placebo.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] Kang, 2017, Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study, Microbiome source

      Not checked in the free run.

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

    Premisecitation

    The 17-question screen relies on caretaker observation and was administered prospectively to caretakers and then to pediatric gastroenterologists who had evaluated the patients.

    “This 17-question screen, which relies on caretaker observation, was administered prospectively to caretakers and then to pediatric gastroenterologists who had evaluated the patients.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Margolis, 2019, Development of a brief parent-report screen for common gastrointestinal disorders in autism spectrum disorder, J Autism Dev Disord source

      Not checked in the free run.

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

    Premisenone given

    The gold standard screening tool used to diagnose some of the most common pediatric GI conditions is the Rome criteria.

    “The gold standard screening tool used to diagnose some of the most common pediatric GI conditions is the Rome criteria.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The Rome criteria are the gold standard screening tool for diagnosing some of the most common pediatric GI conditions.

  • May combine two claims.

    Premisecitation

    Anecdotal reports suggest that effective treatment of GI disorders is important not only for attenuation of GI problems but potential improvements in associated behavioral correlates.

    “These anecdotal reports, however, suggest that effective treatment of GI disorders is important not only for the attenuation of the GI problems, but potential improvements in associated behavioral correlates as well 747677.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [74] Arnold, 2019, Probiotics for gastrointestinal symptoms and quality of life in autism: a placebo-controlled pilot trial, J Child Adolesc Psychopharmacol source

      Not checked in the free run.

    • cites [76] Kang, 2017, Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study, Microbiome source

      Not checked in the free run.

    • cites [77] Kang, 2019, Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota, Sci Rep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Treatment of MIA-exposed mice with Bacteroides fragilis normalizes intestinal permeability, prevents migration of neurotransmitters through the gut wall and improves multiple hallmarks of ASD-like behaviors.

    “Treatment of MIA-exposed mice with Bacteriodes fragilis has been shown to normalize intestinal permeability, prevents migration of neurotransmitters through the gut wall and improves multiple hallmarks of ASD-like behaviors 6870.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [68] Hsiao, 2013, Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders, Cell source

      Not checked in the free run.

    • cites [70] Mazmanian, 2008, A microbial symbiosis factor prevents intestinal inflammatory disease, Nature source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Though not effective as a treatment, the vancomycin study was an important step in linking the microbiome with ASD.

    “Though not effective as a treatment, this was an important step in linking the microbiome with ASD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Early studies on probiotic treatment in children with ASD and GI problems show promise, but larger trials are necessary to better implicate the role of probiotics in ASD treatment.

    “These early studies on probiotic treatment in children with ASD and GI problems thus show promise, but larger trials are necessary to better implicate the role of probiotics in ASD treatment 14.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Buie, 2010, Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report, Pediatrics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Progeny of MIA mice develop phenotypes consistent with ASD, whereas mice with selective deletion of IL-6 in placental trophoblasts had offspring that did not display these neurobiological or behavioral abnormalities.

    “Whereas progeny of MIA mice develop phenotypes consistent with ASD, those mice with selective deletion of IL-6 in placental trophoblasts had offspring that did not display these neurobiological or behavioral abnormalities 71.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [71] Wu, 2017, The placental interleukin-6 signaling controls fetal brain development and behavior, Brain Behav Immun source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Two major reasons for difficulty diagnosing GI problems in ASD are that children with ASD often have limited verbal ability and, even if verbal ability is intact, sensory perception is often abnormal, making it difficult to localize and/or describe sources of discomfort.

    “Two of the major reasons that this occurs is because children with ASD often have limited verbal ability and, even if their verbal ability is intact, sensory perception is often abnormal, making it difficult for these individuals to localize and/or describe sources of their discomfort 72.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [72] Whitney, 2019, National prevalence of pain among children and adolescents with autism spectrum disorders, JAMA Pediatr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Anecdotal reports of behavioral improvements following effective treatment for GI problems exist, but prospective studies are still required.

    “Although there are anecdotal reports of behavioral improvements following effective treatment for GI problems, prospective studies are still required 7475.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [74] Arnold, 2019, Probiotics for gastrointestinal symptoms and quality of life in autism: a placebo-controlled pilot trial, J Child Adolesc Psychopharmacol source

      Not checked in the free run.

    • cites [75] Sanctuary, 2019, Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms, PLoS One source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A concise version of this screening tool was created and validated.

    “Recently, a concise version of this screening tool was created and validated.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Margolis, 2019, Development of a brief parent-report screen for common gastrointestinal disorders in autism spectrum disorder, J Autism Dev Disord source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There are a number of studies that demonstrate a difference in Clostridia levels in children with ASD, which is a target for vancomycin.

    “There are a number of studies, however, that demonstrate a difference in Clostridia levels in children with ASD that, interestingly, is a target for vancomycin 79–82.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [79] Bolte, 1998, Autism and Clostridium tetani, Med Hypotheses source

      Not checked in the free run.

    • cites [80] Rodakis, 2015, An n=1 case report of a child with autism improving on antibiotics and a father's quest to understand what it may mean, Microb Ecol Health Dis

      Not checked in the free run.

    • cites [81] Finegold, 2017, Detection of Clostridium perfringens toxin genes in the gut microbiota of autistic children, Anaerobe source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In that trial, parents reported a significant improvement in GI symptoms, but the overall resulting quality of life measures were not significant.

    “Although parents reported a significant improvement in GI symptoms, the overall resulting quality of life measures were not significant 74.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Arnold, 2019, Probiotics for gastrointestinal symptoms and quality of life in autism: a placebo-controlled pilot trial, J Child Adolesc Psychopharmacol source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    In that study, some patients showed improvements in GI problems and aberrant behaviors, but the small sample size and lack of a true control group makes this data harder to generalize.

    “Although some of these patients showed improvements in GI problems and aberrant behaviors, the small sample size and lack of a true control group makes this data harder to generalize 75.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [75] Sanctuary, 2019, Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms, PLoS One source

      Not checked in the free run.

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

    Interpretationreasoning

    This alludes to a potential mechanism through which maternal immune activation can interfere with gestation.

    “This alludes to a potential mechanism through which MIA can interfere with gestation, opening the door to future research in this area.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    In contrast to the Rome criteria, GI problems were identified in this questionnaire by utilizing observable signs for caretakers, as opposed to verbal complaints, and thus included physical behaviors associated with GI distress.

    “In contrast to the Rome criteria, GI problems were identified in this questionnaire by utilizing observable signs for caretakers, as opposed to verbal complaints, and thus included physical behaviors associated with GI distress (i.e. applying abdominal pressure).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Multiple studies have shown that children with ASD have different intestinal microbiota than neurotypical children, but the studies have been small with variable results.

    “Although multiple studies have shown that children with ASD have different intestinal microbiota than neurotypical children, the studies have been small with variable results 51.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Vuong, 2017, Emerging roles for the gut microbiome in autism spectrum disorder, Biol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    GI problems are common in the ASD population and are morbidity causing.

    “It has become increasingly clear that GI problems are common in the ASD population and also morbidity causing.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationcitation

    Gut microbiota modulation may be a distinct novel therapeutic option for children with ASD in the future, as a treatment for not only GI problems but behavioral issues as well.

    “Although not a currently recommended treatment, gut microbiota modulation (i.e. FMT, probiotics, etc.) may be a distinct novel therapeutic option for this population in the future, as a treatment for not only GI problems but behavioral issues as well.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisereasoning

    Treatment for GI conditions in ASD is similar in many ways to treatment for neurotypical individuals, but additional considerations must be made.

    “Although the treatment for GI conditions in ASD is similar in many ways to those of neurotypical individuals, additional considerations must be made.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Treatment for GI conditions in children with ASD is similar in many ways to treatment for neurotypical individuals.
41 of 41

  • The paper relies on this without support.

    The Rome criteria are the gold standard screening tool for diagnosing some of the most common pediatric GI conditions.

    “The gold standard screening tool used to diagnose some of the most common pediatric GI conditions is the Rome criteria.”

  • The paper relies on this without support.

    The Autism Treatment Network GI symptom inventory questionnaire diagnoses the most common GI conditions found in ASD.

    “In order to facilitate more accurate diagnoses in the ASD population, the Autism Treatment Network created a GI symptom inventory questionnaire to diagnose the most common GI conditions found in ASD.”

  • The paper relies on this without support.

    Treatment for GI conditions in children with ASD is similar in many ways to treatment for neurotypical individuals.

    “Although the treatment for GI conditions in ASD is similar in many ways to those of neurotypical individuals, additional considerations must be made.”
3 of 3

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Cites

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Research works printed but not linked: 1

  1. Kanner, 1968, Austic disturbances of affective contact, Acta Paedopsychiatr, 35, 100

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Authors
Madra, M., Ringel, R., & Margolis, K. G.
Affiliations
Morgan Stanley Children's Hospital (US)
Corresponding author
Margolis, Kara Gross
ORCID
Venue
Child and Adolescent Psychiatric Clinics of North America
Publisher
Elsevier BV
Published
2020-07
Volume
29
Issue
3
Pages
501-513
ISSN
1056-4993 (ISSN-L)
DOI
10.1016/j.chc.2020.02.005
PMC
PMC8608248
OpenAlex
W3014608586
Semantic Scholar
a28ed6fc2d63ef3637ef3c27be42bac78a233608
Cited by
159
References
81
Citations by year
2026: 29 · 2025: 40 · 2024: 37 · 2023: 28 · 2022: 16 · 2021: 8 · 2020: 1
FWCI
1.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Child and Adolescent Psychiatric Clinics of North America (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Defense
  • National Institutes of Health
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
autism spectrum disorder, gastrointestinal diseases, comorbidities, symptom severity, quality of life, behavioral effects, risk factors, treatment
MeSH terms
Autism Spectrum Disorder, Feeding and Eating Disorders, Diarrhea, Gastrointestinal Diseases, Humans, Quality of Life, Comorbidity

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 2026-10-10.

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

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 ›

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