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Cited by 214Gut microbiota and healthAutism Spectrum Disorder ResearchChild Nutrition and Feeding Issues

Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions

Open access
Ristori, Maria Vittoria, Quagliariello, Andrea, Reddel, Sofia, Ianiro, Gianluca, Vicari, Stefano, Gasbarrini, Antonio, Putignani, Lorenza·2019·Nutrients
DOI 10.3390/nu11112812PMC PMC6893818
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Abstract

Autism spectrum disorder (ASD) is a complex behavioral syndrome that is characterized by speech and language disorders, intellectual impairment, learning and motor dysfunctions. Several genetic and environmental factors are suspected to affect the ASD phenotype including air pollution, exposure to pesticides, maternal infections, inflammatory conditions, dietary factors or consumption of antibiotics during pregnancy. Many children with ASD shows abnormalities in gastrointestinal (GI) physiology, including increased intestinal permeability, overall microbiota alterations, and gut infection. Moreover, they are “picky eaters” and the existence of specific sensory patterns in ASD patients could represent one of the main aspects in hampering feeding. GI disorders are associated with an altered composition of the gut microbiota. Gut microbiome is able to communicate with brain activities through microbiota-derived signaling molecules, immune mediators, gut hormones as well as vagal and spinal afferent neurons. Since the diet induces changes in the intestinal microbiota and in the production of molecules, such as the SCFA, we wanted to investigate the role that nutritional intervention can have on GI microbiota composition and thus on its influence on behavior, GI symptoms and microbiota composition and report which are the beneficial effect on ASD conditions.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review examines links among autism spectrum disorder (ASD), gastrointestinal symptoms, gut microbiota, and nutritional interventions. It concludes that food selectivity and altered microbiota/metabolite pathways may contribute to GI and behavioral symptoms, but evidence for specific diets remains limited.

Key findings

  • GI symptoms are common but variably reported in ASD, with prevalence ranging from 23% to 70%; in one study of 150 children, 70% of ASD children had GI symptoms versus 28% of typically developing children and 42% of children with other developmental disabilities, and studies of 140–170 ASD children found 24–63% had at least one GI symptom.
  • Food selectivity in ASD is driven by texture (69%), appearance (58%), taste (45%), smell (36%), temperature (22%), reluctance to try new foods (69%), and a small repertoire of accepted foods (60%); presentation factors were reported at 48.6% and utensil/tableware characteristics at 13.8%, and nearly 90% of preschool and school-age ASD children were reported not to process sensory information the same way as typically developing peers.
  • ASD children show altered gut microbiota profiles, including reduced relative abundance of *Prevotella*, *Coprococcus*, *Enterococcus*, *Lactobacillus*, *Streptococcus*, *Lactococcus*, *Staphylococcus*, *Ruminococcus*, and *Bifidobacterium*, and higher *Clostridia*, *Desulfovibrio*, *Sutterella*, and *Ruminococcus torques*; one study of 40 ASD and 40 non-ASD participants found *Candida* representation up to 2 times greater in ASD.
  • Proposed metabolite pathways include elevated acetic acid and propionic acid, lower butyric acid, increased SCFA-producing bacteria, and elevated whole-blood/platelet serotonin in approximately 30% of children with ASD; dietary evidence is mixed or limited for gluten-free/casein-free diet, ketogenic diet, and specific carbohydrate diet, and no studies were found on the Mediterranean diet in ASD patients.

Methods

  • Design: narrative literature review conducted on PubMed from 1955 to 2019 using terms including “autism,” “autism spectrum disorder,” “diet,” “nutritional status,” “microbiota,” “microbiome,” “metabolites,” “dysbiosis,” and “gastrointestinal symptoms.”
  • Inclusion criteria: observational prospective and retrospective studies, case–control studies, cohort studies, or systematic reviews; studies investigating gut microbiota profiles and metabolites in ASD children; studies with information on nutritional intervention or nutritional status in ASD patients; and studies written in English.
  • Analysis: qualitative synthesis of included literature; no meta-analysis or quantitative pooling is described.

Limitations

  • The paper states that evidence for gluten-free/casein-free diet is limited and inadequate in quantity, quality, and methodological rigor; ketogenic diet evidence is based on a limited number of reports and is insufficient to establish practicability; specific carbohydrate diet evidence comes from few studies, including one case report; and no studies were found on the Mediterranean diet in ASD patients.
  • The paper states that GI symptom prevalence varies widely due to differences in criteria, symptoms considered, data sources, reporting periods, and population characteristics, and that dietary data may be inaccurate because parental concern may influence reporting; it also states that the physiological processes linking food selectivity and GI problems remain difficult to decipher.
  • Evident from the text: as a narrative review, it does not report a systematic quality appraisal, risk-of-bias assessment, or meta-analysis, and many cited intervention findings are small, animal-based, or case-level.

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

Integrity signals

Registry

Crossref · 10.3390/nu11112812

Cites

202 of 202 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 197 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    GI disorders such as intestinal pain, constipation, and diarrhea are often associated with an altered composition of the gut microbiota.

    “GI disorders such as intestinal pain, constipation and diarrhea are often associated with an altered composition of the gut microbiota [28,132,140,141,142].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [28] McElhanon, 2014, Gastrointestinal Symptoms in Autism Spectrum Disorder: A Meta-analysis, Pediatrics source

      Not checked in the free run.

    • cites [132] Adams, 2006, Analyses of toxic metals and essential minerals in the hair of Arizona children with autism and associated conditions, and their mothers, Biol. Trace Elem. Res. source

      Not checked in the free run.

    • cites [140] Adams, 2007, Mercury, lead, and zinc in baby teeth of children with autism versus controls, J. Toxicol. Environ. Health Part A source

      Not checked in the free run.

    • cites [141] Konstantareas, 1987, Ear infections in autistic and normal children, J. Autism Dev. Disord. source

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    • cites [142] Niehus, 2006, Early medical history of children with autism spectrum disorders, J. Dev. Behav. Pediatr. source

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  • Premisecitation

    There is a positive correlation between sensory overresponsivity in ASDs and the severity level of food selectivity, expressed by number of foods accepted by the child.

    “Miller identified three different cluster of modulating sensory sensitivity in ASDs and found a positive correlation between sensory overresponsivity (SOR) in ASDs and the severity level of food selectivity, expressed by number of foods accepted by the child [66].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Miller, 2007, Concept evolution in sensory integration: A proposed nosology for diagnosis, Am. J. Occup. Ther. source

      Not checked in the free run.

  • Premisecitation

    The gut microbiome communicates with brain activities through microbiota-derived signaling molecules, immune mediators, gut hormones, and vagal and spinal afferent neurons.

    “Recent evidences in human gut microbiota studies highlighted the existence of a close connection between gut and brain functions, the so called “gut-brain axis”, including neural, hormonal, immune, and metabolic pathways [45].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Berding, 2016, Microbiome and nutrition in autism spectrum disorder: Current knowledge and research needs, Nutr. Rev. source

      Not checked in the free run.

  • Interpretationreasoning

    To date, evidence to support or refute GF/CF diet in ASD is limited and inadequate in quantity, quality, and multiple methodological limitations of studies in the literature.

    “To date evidence to support or refute GF/CF in ASD is limited and inadequate in terms of quantity, quality and multiple methodological limitations of studies in the literature.”
    Quote in the paperSubstantial claim
  • Premisecitation

    A substantial number of subjects with ASDs had inadequate intakes of micronutrients, including deficiencies of calcium, iron, zinc, potassium, copper, vitamin A, vitamin D, vitamin E, riboflavin, vitamin C, vitamin B-12, folic acid, and choline.

    “Substantial number of subjects with ASDs had inadequate intakes of micronutrients.”
    • Also stated in: § 3.2. Nutrient Intake and ASDs. · plain
      “In particularly they showed deficiencies of few minerals such as calcium [67,69,71,73,75,77,79], iron [73,77], zinc [75,77,80], potassium [81], copper [81] and vitamins as vitamin A [71,75,77], vitamin D [67,69,73,78], vitamin E [71,73], riboflavin [77], vitamin C [75,78], vitamin B-12 [69,77,82], folic acid [75,82], and choline [80,83].”
    Quote in the paperNot a substantial claim0 of 8 sources checked
    • cites [67] Bandini, 2010, Food selectivity in children with autism spectrum disorders and typically developing children, J. Pediatr. source

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    • cites [69] Zimmer, 2012, Food variety as a predictor of nutritional status among children with autism, J. Autism Dev. Disord. source

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    • cites [71] Lockner, 2008, Dietary intake and parents’ perception of mealtime behaviors in preschool-age children with autism spectrum disorder and in typically developing children, J. Am. Diet. Assoc. source

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    • cites [73] Herndon, 2009, Does nutritional intake differ between children with autism spectrum disorders and children with typical development?, J. Autism Dev. Disord. source

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    • cites [75] Xia, 2010, A preliminary study on nutritional status and intake in Chinese children with autism, Eur. J. Pediatr. source

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    • cites [77] Cornish, 2002, Gluten and casein free diets in autism: A study of the effects on food choice and nutrition, J. Hum. Nutr. Diet. source

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    • cites [79] Bicer, 2013, Body mass index, dietary intake and feeding problems of Turkish children with autism spectrum disorder (ASD), Res. Dev. Disabil. source

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    • cites [80] Hyman, 2012, Nutrient intake from food in children with autism, Pediatrics source

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  • Classified as probably not a substantial claim. 8
  • May combine two claims. 52

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

    Findingnone given

    No studies have reported the effect of Mediterranean diet on ASD patients.

    “Actually, at our knowledge, no studies have reported the effect of MD on ASD patients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Many studies show ASD children have a considerably smaller variety of foods but no overall differences in total calories, carbohydrates, or fat intakes compared with typically developing children, suggesting satiety mechanisms are not impaired.

    “However, in many studies children with ASDs show a considerably smaller variety of foods, but authors report no overall differences in their total calories, carbohydrates, or fat intakes [62,71,72,73,74], suggesting that their satiety mechanisms are not impaired.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [62] Schmitt, 2008, A Comparison of Nutrient Intake and Eating Behaviors of Boys with and Without Autism, Top. Clin. Nutr. source

      Not checked in the free run.

    • cites [71] Lockner, 2008, Dietary intake and parents’ perception of mealtime behaviors in preschool-age children with autism spectrum disorder and in typically developing children, J. Am. Diet. Assoc. source

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    • cites [72] Emond, 2010, Feeding symptoms, dietary patterns, and growth in young children with autism spectrum disorders, Pediatrics source

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    • cites [73] Herndon, 2009, Does nutritional intake differ between children with autism spectrum disorders and children with typical development?, J. Autism Dev. Disord. source

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    • cites [74] Levy, 2007, Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders, Biol. Psychiatry source

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    Premisecitation

    Food selectivity in ASD leads to inadequate caloric intake and nutritional deficits.

    “From a nutritional point of view this leads to an inadequate caloric intake and hence to nutritional deficits [49,50].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [49] Markham, 2010, Feeding and eating disorders in childhood, Int. J. Eat. Disord. source

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    • cites [50] Kreipe, 2012, Beyond picky eating: Avoidant/restrictive food intake disorder, Curr. Psychiatry Rep. source

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    Premisecitation

    Increased consumption of snack foods and calorie-dense foods can lead to excessive weight gain, with higher rates of obesity in ASD children than in unaffected children.

    “Increased consumption of snack foods and calorie-dense foods can lead to excessive weight gain, with related higher rates of obesity in ASD children than in unaffected children [58].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] Berry, 2015, Nutrition Management of Gastrointestinal Symptoms in Children with Autism Spectrum Disorder: Guideline from an Expert Panel, J. Acad. Nutr. Diet. source

      Not checked in the free run.

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    Premisecitation

    Food selectivity is determined by texture (69%), appearance (58%), taste (45%), smell (36%), temperature (22%), reluctance to try new foods (69%), and a small repertoire of accepted foods (60%).

    “studies have indicated that food selectivity is being determined by the following factors: texture (69%), appearance (58%), taste (45%), smell (36%), and temperature (22%), as well as reluctance to try new foods (69%) and a small repertoire of accepted foods (60%) (Figure 1) [52,53,54,55].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [52] Williams, 2000, Eating habits of children with autism, Pediatr. Nurs.

      Not checked in the free run.

    • cites [53] Schreck, 2006, Food preferences and factors influencing food selectivity for children with autism spectrum disorders, Res. Dev. Disabil. source

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    • cites [54] Klein, 1999, Characteristics of patients with autistic disorder (AD) presenting for dental treatment: A survey and chart review, Spec. Care Dentist. source

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    • cites [55] Zazpe, 2014, Food selectivity in autism spectrum disorders: A systematic review, J. Child Neurol. source

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

    Premisecitation

    Nearly 90% of preschool and school-age ASD children do not process sensory information related to touch, smell, sight, and hearing in the same way as typically developing peers.

    “Nadon et al. found that nearly 90% of preschool and school age ASD children do not process sensory information, in particular related to touch, smell, sight, and hearing, in the same way as their typically developing peers [60].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Nadon, 2011, Mealtime problems in children with autism spectrum disorder and their typically developing siblings: A comparison study, Autism source

      Not checked in the free run.

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    Premisecitation

    Children with ASD are very selective eaters and most show aversions to specific food colors, textures, smells, or other food characteristics.

    “Indeed, children with ASD are very selective eaters (“picky eaters”) and most of them show aversions to specific food colors, texture, smells or other foods’ characteristics [26,27].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [26] Horvath, 2002, Autistic disorder and gastrointestinal disease, Curr. Opin. Pediatr. source

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    • cites [27] Cermak, 2010, Food Selectivity and Sensory Sensitivity in Children with Autism Spectrum Disorders, J. Am. Diet. Assoc. source

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    Premisecitation

    Protein intake in ASD children is adequate or quite similar to that of typically developing children.

    “Protein intake was adequate or quite similar to that of typically developing children [69,72,73,74,75,76,77].”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [69] Zimmer, 2012, Food variety as a predictor of nutritional status among children with autism, J. Autism Dev. Disord. source

      Not checked in the free run.

    • cites [72] Emond, 2010, Feeding symptoms, dietary patterns, and growth in young children with autism spectrum disorders, Pediatrics source

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    • cites [73] Herndon, 2009, Does nutritional intake differ between children with autism spectrum disorders and children with typical development?, J. Autism Dev. Disord. source

      Not checked in the free run.

    • cites [74] Levy, 2007, Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders, Biol. Psychiatry source

      Not checked in the free run.

    • cites [75] Xia, 2010, A preliminary study on nutritional status and intake in Chinese children with autism, Eur. J. Pediatr. source

      Not checked in the free run.

    • cites [76] Johnson, 2008, Eating habits and dietary status in young children with autism, J. Dev. Phys. Disabil. source

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    • cites [77] Cornish, 2002, Gluten and casein free diets in autism: A study of the effects on food choice and nutrition, J. Hum. Nutr. Diet. source

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  • May combine two claims.

    Premisecitation

    A strong preference for starches, snacks, and processed foods, along with rejection of fruits, vegetables, or protein, is common in ASD.

    “A strong preference for starches, snacks and processed foods, along with a rejection of fruits, vegetables or protein, is particularly common [56,57].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [56] Sharp, 2013, Feeding problems and nutrient intake in children with autism spectrum disorders: A meta-analysis and comprehensive review of the literature, J. Autism. Dev. Disord. source

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    • cites [57] Curtin, C., Anderson, S.E., Must, A., and Bandini, L. (2010). The prevalence of obesity in children with autism: A secondary data analysis using nationally representative data from the National Survey of Children’s Health. BMC Pediatr., 10. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Many children with ASD show abnormalities in GI physiology, including increased intestinal permeability, overall microbiota alterations, and gut infection with cresol-producing Clostridium difficile.

    “Many ASD children have also been shown to carry abnormalities in GI physiology, including: increased intestinal permeability [34,35], overall microbiota alterations [36,37,38,39,40], and gut infection with cresol-producing Clostridium difficile [39,41,42,43,44].”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [34] Celli, 1996, Abnormal intestinal permeability in children with autism, Acta Paediatr. source

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    • cites [35] Familiari, 2010, Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives, J. Pediatr. Gastroenterol. Nutr. source

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    • cites [36] De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D.I., Cristofori, F., Guerzoni, M.E., Gobbetti, M., and Francavilla, R. (2013). Fecal Microbiota and Metabolome of Children with Autism and Pervasive Developmental Disorder Not Otherwise Specified. PLoS ONE, 8. source

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    • cites [37] Finegold, 2010, Pyrosequencing study of fecal microflora of autistic and control children, Anaerobe source

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    • cites [38] Mulle, 2013, The Gut Microbiome: A New Frontier in Autism Research, Curr. Psychiatry Rep. source

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    • cites [39] Parracho, 2005, Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children, J. Med. Microbiol. source

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    • cites [40] Wang, 2011, Normal gut microbiota modulates brain development and behavior, Proc. Natl. Acad. Sci. USA source

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    • cites [41] Elsden, 1976, The end products of the metabolism of aromatic amino acids by Clostridia, Arch. Microbiol. source

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    • cites [42] Finegold, 2002, Gastrointestinal microflora studies in late-onset autism, Clin. Infect. Dis. source

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    • cites [43] Selmer, 2001, p-Hydroxyphenylacetate decarboxylase from Clostridium difficile. A novel glycyl radical enzyme catalysing the formation of p-cresol, Eur. J. Biochem. source

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  • May combine two claims.

    Interpretationreasoning

    Food selectivity and altered elaboration of sensory stimuli could imply a higher risk of nutritional deficiencies that could, in turn, affect gastrointestinal symptoms and microbiota.

    “Overall, the available evidence suggests that this food selectivity and an altered elaboration of sensory stimuli could imply a higher risk of nutritional deficiencies that could, in turn, affect gastrointestinal symptom and microbiota.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ASD children eat fewer vegetables and more energy-dense foods, so fiber intake is inadequate in a considerable number of children with ASD.

    “Children with ASDs eat fewer vegetables and eat more energy-dense foods [76,78], so fiber intake was inadequate in a considerable number of children with ASDs [71,73,79,80].”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [76] Johnson, 2008, Eating habits and dietary status in young children with autism, J. Dev. Phys. Disabil. source

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    • cites [78] Evans, 2012, Dietary Patterns and Body Mass Index in Children with Autism and Typically Developing Children, Res. Autism Spectr. Disord. source

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    • cites [71] Lockner, 2008, Dietary intake and parents’ perception of mealtime behaviors in preschool-age children with autism spectrum disorder and in typically developing children, J. Am. Diet. Assoc. source

      Not checked in the free run.

    • cites [73] Herndon, 2009, Does nutritional intake differ between children with autism spectrum disorders and children with typical development?, J. Autism Dev. Disord. source

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    • cites [79] Bicer, 2013, Body mass index, dietary intake and feeding problems of Turkish children with autism spectrum disorder (ASD), Res. Dev. Disabil. source

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    • cites [80] Hyman, 2012, Nutrient intake from food in children with autism, Pediatrics source

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

    Premisecitation

    The ketogenic diet is an effective treatment for epileptic patients who fail to respond to anticonvulsant medications.

    “The KD is a high fat and low-carbohydrate diet and it is an effective treatment for epileptic patients that fails in responding to anticonvulsant medications [84].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Castro, 2015, Effect of a ketogenic diet on autism spectrum disorder: A systematic review, Res. Autism Spectr. Disord. source

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    Premisecitation

    Administration of ketogenic diet to individuals with ASD showed positive effects especially for mild and moderate cases and some reports of improvements in seizure symptoms and behavioral deficits.

    “The administration of KD to individuals with ASD underlined positive effects especially for mild and moderate cases and some reports of improvements in seizure symptoms and behavioral deficits [84,107].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [84] Castro, 2015, Effect of a ketogenic diet on autism spectrum disorder: A systematic review, Res. Autism Spectr. Disord. source

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    • cites [107] Evangeliou, 2003, Application of a ketogenic diet in children with autistic behavior: Pilot study, J. Child Neurol. source

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  • May combine two claims.

    Premisecitation

    Some studies reported decreased bone development, lower mineral density, and greater risk of fractures in children with ASD compared to controls, linked to lack of calcium and vitamin D in the diet, despite good anthropometric growth.

    “Some studies reported decreased bone development lower mineral density and a greater risk of fractures in children with ASD compared to controls (TDs), linked to a lack of calcium and vitamin D in the diet, despite good anthropometric growth [85,86,87,88].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [85] Hediger, 2008, Reduced bone cortical thickness in boys with autism or autism spectrum disorder, J. Autism Dev. Disord. source

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    • cites [86] Neumeyer, 2015, Brief report: Bone fractures in children and adults with autism spectrum disorders, J. Autism Dev. Disord. source

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    • cites [87] Clark, 1993, Symptomatic vitamin A and D deficiencies in an eight-year-old with autism, J. Parenter. Enter. Nutr. source

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    • cites [88] Stewart, 2008, Symptomatic nutritional rickets in a teenager with autistic spectrum disorder, Child Care Health Dev. source

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  • May combine two claims.

    Premisecitation

    In healthy subjects, gluten-free diet is associated with reduction of beneficial gut bacteria populations, increase in opportunistic pathogens, and immune-suppressive effects.

    “Evidences on healthy subjects showed that gluten-free diet has been associated with the reduction of beneficial gut bacteria populations, the increase in opportunistic pathogens and with immune-suppressive effects [100,101,102].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [100] Nistal, 2012, Differences of small intestinal bacteria populations in adults and children with/without celiac disease: Effect of age, gluten diet, and disease, Inflamm. Bowel Dis. source

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    • cites [101] Di Cagno, R., De Angelis, M., De Pasquale, I., Ndagijimana, M., Vernocchi, P., Ricciuti, P., Gagliardi, F., Laghi, L., Crecchio, C., and Guerzoni, M.E. (2011). Duodenal and faecal microbiota of celiac children: Molecular, phenotype and metabolome characterization. BMC Microbiol., 11. source

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    • cites [102] Nadal, 2009, Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects, Br. J. Nutr. source

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    Premisecitation

    In ASD cohorts, some evidence supports use of GF/CF diet in amelioration of ASD symptoms, showing decreases in urine peptides, improved behavior, and decreased GI symptoms.

    “some evidence supports the use of this diet in the amelioration of ASD symptoms showing that the GF/CF diet decreases urine peptides, improves behavior [105] and decreases GI symptoms [106]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [105] Reichelt, 2009, The possibility and probability of a gut-to-brain connection in autism, Ann. Clin. Psychiatry

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    • cites [106] Ghalichi, 2016, Effect of gluten free diet on gastrointestinal and behavioral indices for children with autism spectrum disorders: A randomized clinical trial, World J. Pediatr. source

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  • May combine two claims.

    Interpretationreasoning

    Food selectivity and inadequate nutrient intake could increase the risk of malnutrition in ASDs, ultimately leading to either obesity or undernutrition.

    “Therefore food selectivity and an inadequate nutrient intake could increase the risk of malnutrition in ASDs that ultimately leads to either obesity or undernutrition.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Excessive sodium consumption was reported in ASD, probably due to consumption of packaged foods.

    “Excessive consumption of sodium was reported [79,84], probably due to the consumption of packaged foods.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [79] Bicer, 2013, Body mass index, dietary intake and feeding problems of Turkish children with autism spectrum disorder (ASD), Res. Dev. Disabil. source

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    • cites [84] Castro, 2015, Effect of a ketogenic diet on autism spectrum disorder: A systematic review, Res. Autism Spectr. Disord. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Some studies highlight higher abundance of Clostridia and Desulfovibrio bacteria and a lower ratio of Bacteroidetes to Firmicutes in ASD.

    “In the scientific literature, some studies highlight a higher abundance of Clostridia and Desulfovibrio bacteria and a lower ratio of Bacteroidetes to Firmicutes in ASD [37,39,143,145].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [37] Finegold, 2010, Pyrosequencing study of fecal microflora of autistic and control children, Anaerobe source

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    • cites [39] Parracho, 2005, Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children, J. Med. Microbiol. source

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    • cites [143] Kang, D.W., Park, J.G., Ilhan, Z.E., Wallstrom, G., Labaer, J., Adams, J.B., and Krajmalnik-Brown, R. (2013). Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS ONE, 8. source

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    • cites [145] Tomova, 2015, Gastrointestinal microbiota in children with autism in Slovakia, Physiol. Behav. source

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  • May combine two claims.

    Premisecitation

    In ADHD, high consumption of sugar and candy, cola beverages, and noncola soft drinks and low consumption of fatty fish were associated with higher prevalence of ADHD diagnosis.

    “In addition, a high consumption of sugar and candy, cola beverages, and noncola soft drinks and a low consumption of fatty fish were also associated with a higher prevalence of ADHD diagnosis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [123] Alda, 2017, The Mediterranean Diet and ADHD in Children and Adolescents, Pediatrics source

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  • May combine two claims.

    Premisecitation

    In a study of 150 children (50 ASD, 50 controls, 50 with other developmental disabilities), 70% of children with ASD presented GI symptoms, compared to 28% of typically developing children and 42% of DD children.

    “Another study on 150 children (50 ASD, 50 controls, and 50 children with other developmental disabilities (DD)) found that 70% of children with ASD presented GI symptoms, compared to 28% of typically developing children and 42% of DD children [126].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [126] McVicar, 2006, Frequency of gastrointestinal symptoms in children with autistic spectrum disorders and association with family history of autoimmune disease, J. Dev. Behav. Pediatr. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Food selectivity can exacerbate or determine GI symptoms such as constipation due to a diet rich in carbohydrates and poor in fiber that does not promote intestinal transit.

    “Moreover, food selectivity can exacerbate or determine GI symptoms (e.g., constipation) due to a diet rich in carbohydrates and poor in fiber that do not promote intestinal transit and can lead to constipation [127].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] Ibrahim, 2009, Incidence of gastrointestinal symptoms in children with autism: A population-based study, Pediatrics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ASD children have altered gut microbiota profiles compared with NT children, although some studies report no significant difference.

    “In the literature it has been reported that ASD children have altered gut microbiota profiles compared with NT children, although in some studies, no significant difference has been reported [19,20]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] Obrenovich, 2011, Altered heavy metals and transketolase found in autistic spectrum disorder, Biol. Trace Elem. Res. source

      Not checked in the free run.

    • cites [20] Splawski, 2006, CACNA1H mutations in autism spectrum disorders, J. Biol. Chem. source

      Not checked in the free run.

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

    Premisecitation

    The specific carbohydrate diet was developed in the 1930s for patients with celiac disease but is also employed to treat Crohn's disease, ulcerative colitis, diverticulitis, and chronic diarrhea.

    “The SCD was developed in the 1930s as a dietary protocol intended for patients with celiac disease [111] but it is also employed to treat Crohn’s disease, ulcerative colitis, diverticulitis and chronic diarrhea [112,113,114].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [111] Haas, 1955, The treatment of celiac disease with the specific carbohydrate diet; report on 191 additional cases, Am. J. Gastroenterol.

      Not checked in the free run.

    • cites [112] Gottschall, 2004, Digestion-gut-autism connection: The Specific Carbohydrate Diet, Med. Veritas J. Med. Truth source

      Not checked in the free run.

    • cites [113] Suskind, 2014, Nutritional therapy in pediatric Crohn disease: The specific carbohydrate diet, J. Pediatr. Gastroenterol. Nutr. source

      Not checked in the free run.

    • cites [114] Obih, 2016, Specific carbohydrate diet for pediatric inflammatory bowel disease in clinical practice within an academic IBD center, Nutrition source

      Not checked in the free run.

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

    Premisecitation

    Low adherence to the Mediterranean diet is associated with odds of an ADHD diagnosis in children and adolescents.

    “This was the first study showing that low adherence to the MD is associated with odds of an ADHD diagnosis in children and adolescents.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [123] Alda, 2017, The Mediterranean Diet and ADHD in Children and Adolescents, Pediatrics source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Abdominal pain, constipation, and/or diarrhea likely produce frustration and may contribute to severity of the disorder, with decreased ability to concentrate, behavior problems, and possibly aggression and self-abuse, especially in children unable to communicate discomfort.

    “Indeed, abdominal pain, constipation, and/or diarrhea likely to produce frustration and may contribute to the severity of the disorder, with decreased ability to concentrate on tasks, behavior problems, and possibly aggression and self-abuse, especially in children unable to communicate their discomfort [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Adams, J.B., Johansen, L.J., Powell, L.D., Quig, D., and Rubin, R.A. (2011). Gastrointestinal flora and gastrointestinal status in children with autism—Comparisons to typical children and correlation with autism severity. BMC Gastroenterol., 11. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ketogenic diet treatment of BTBR mice improved deficits related to myelin formation and white matter development/connectivity, acting on neurotransmitter signaling pathways including glutamate, serotonin, neuronal nitric acid synthase, and dopamine.

    “KD treatment of BTBR mice also improved deficits typical of ASD related to myelin formation and white matter development/connectivity, acting on neurotransmitter signaling pathways including glutamate, serotonin, neuronal nitric acid synthase, and dopamine [109].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [109] Mychasiuk, 2017, Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder, Autism Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    One study examined implementation of a specific carbohydrate diet in a 4-year-old child with ASD and fragile X syndrome, showing the diet was well tolerated and led to improvements in growth status, gastrointestinal symptoms, and behaviors.

    “We found one study that examined the implementation of an SCD protocol in a child with ASD, which showed that the SCD protocol was well tolerated in this 4 year old child diagnosed with ASD and fragile X syndrome (FXS), leading to improvements in growth status, gastrointestinal symptoms, and behaviors [112].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [112] Gottschall, 2004, Digestion-gut-autism connection: The Specific Carbohydrate Diet, Med. Veritas J. Med. Truth source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A 2009 longitudinal study up to 18 years did not report increased risk of GI diseases of inflammatory and/or malabsorption nature in ASD compared to typical development controls; the only significant difference was higher incidence of food selectivity and constipation in ASD.

    “However, a study conducted in 2009 on people with ASD followed longitudinally up to 18 years, did not report an increased risk of GI diseases of an inflammatory and/or malabsorption nature compared to the typical development controls; the only significant difference found was the higher incidence of food selectivity and constipation in ASD people [127].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] Ibrahim, 2009, Incidence of gastrointestinal symptoms in children with autism: A population-based study, Pediatrics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Accumulation of SCFAs, specifically propionate, has broad effects on nervous system physiology and is associated with the pathogenesis of ASD.

    “However, the accumulation of SCFAs, and specifically of propionate, has also been shown to have broad effects on the nervous system physiology, and it is associated to the pathogenesis of ASD [175,176].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [175] Thomas, 2012, The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: Further development of a rodent model of autism spectrum disorders, J. Neuroinflamm. source

      Not checked in the free run.

    • cites [176] MacFabe, 2015, Enteric short-chain fatty acids: Microbial messengers of metabolism, mitochondria, and mind: Implications in autism spectrum disorders, Microb. Ecol. Health Dis.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Other studies observed in ASD children high abundance of Akkermansia muciniphilia, Desulfovibrio, and Faecalibacterium prausnitzii.

    “Others studies observed, in ASD children, high abundance of: Akkermansia muciniphilia, [36,143,148] Desulfovibrio, [37] and Faecalibacterium prausnitzii [36].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [36] De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D.I., Cristofori, F., Guerzoni, M.E., Gobbetti, M., and Francavilla, R. (2013). Fecal Microbiota and Metabolome of Children with Autism and Pervasive Developmental Disorder Not Otherwise Specified. PLoS ONE, 8. source

      Not checked in the free run.

    • cites [143] Kang, D.W., Park, J.G., Ilhan, Z.E., Wallstrom, G., Labaer, J., Adams, J.B., and Krajmalnik-Brown, R. (2013). Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS ONE, 8. source

      Not checked in the free run.

    • cites [148] Xu, 2019, Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis, Front. Psychiatry source

      Not checked in the free run.

    • cites [37] Finegold, 2010, Pyrosequencing study of fecal microflora of autistic and control children, Anaerobe source

      Not checked in the free run.

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

    Premisecitation

    SCFAs (acetic acid, propionic acid, butyric acid) are fermentation end-products of non-digested carbohydrates in the colon and have been suggested to have health benefits related to weight control, lipid profiles, and colon health.

    “Short-chain fatty acids (SCFAs) as acetic acid (AA), propionic acid (PPA), and butyric acid (BA), are the fermatation end-products of non-digested carbohydrates in the colon and have been suggested to have various health benefits to the host related to weight control, lipid profiles, and colon health [174].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [174] Byrne, 2015, The role of short chain fatty acids in appetite regulation and energy homeostasis, Int. J. Obes. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Microbiota and their ligands are crucial in maintaining cell-cell junctions critical to barrier integrity, with GI barrier defects seen with dysbiosis.

    “Indeed, microbiota and their ligands are crucial in maintaining the cell–cell junctions critical to barrier integrity, with GI barrier defects seen with dysbiosis [144].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [144] 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

    A recent study on 40 people with ASD and 40 NT controls confirmed a different bacterial composition of the GI tract and altered fungal colonization, with genus Candida up to 2 times greater than in the control population.

    “A recent study, conducted on a set of 40 people with ASD and a control group of 40 NT, confirmed a different bacterial composition of the GI tract, but also showed an altered fungal colonization, in particular, the genus Candida was identified as the most important distribution, with a representation up to 2 times greater than that of the control population [149].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [149] Strati, 2017, New evidences on the altered gut microbiota in autism spectrum disorders, Microbiome source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Higher intestinal permeability allows an increase in circulating bacteria-derived lipopolysaccharide, leading to an immunological and inflammatory response with augmented systemic pro-inflammatory cytokines.

    “Moreover, a higher intestinal permeability allow the increase in circulating bacteria-derived lipopolysaccharide (LPS) which leads to an immunological and inflammatory response, with an augmented systemic pro-inflammatory cytokines [151].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [151] Qin, 2007, Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration, Glia source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In early adolescent mice, modification of the intestinal microbiota alters behavior and significantly reduces BDNF, oxytocin, and vasopressin expression in the adult brain.

    “A study conducted on early adolescence in mice showed that the modification of the intestinal microbiota alters their behavior and significantly reduces the neurotrophic factor (BDNF), oxytocin and vasopressin expression in the adult brain [166].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [166] Desbonnet, 2015, Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour, Brain Behav. Immun. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Candida spp., Streptococcus spp., Escherichia spp., and Enterococcus spp. produce serotonin.

    “Candida spp., Streptococcus spp., Escherichia spp. and Enterococcus spp. produce serotonin;”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [172] Dinan, 2013, Melancholic microbes: A link between gut microbiota and depression?, Neurogastroenterol. Motil. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Communication between the gut and the brain is bidirectional, and the intestinal microbiota can control CNS activity through neural, endocrine, immune, and metabolic mechanisms that may influence behaviours typical of ASD patients.

    “However, communication is bidirectional and the intestinal microbiota is able to control the activity of the CNS through neural, endocrine, immune, and metabolic mechanisms that could have a possible influence on behaviours typical of ASD patients. [156].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [156] Wang, 2014, The role of microbiome in central nervous system disorders, Brain Behav. Immun. source

      Not checked in the free run.

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

    Premisecitation

    The HPA axis releases cortisol, which regulates intestinal motility and integrity, and hypersecretion of CRH is a crucial factor in depression and anxiety disorders.

    “Furthermore, the hypothalamic–pituitary–adrenal (HPA) axis releases cortisol, which regulates intestinal motility, integrity and hypersecretion of CRH is a crucial factor in depression and anxiety disorders [155].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [155] Trevarthen, 2006, Collaborative Regulations of Vitality in Early Childhood: Stress in Intimate Relationships and Postnatal Psychopathology, Developmental Psychopathology

      Not checked in the free run.

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

    Premisecitation

    The role of microglia deficits in neurological development disorders in a mouse model has emerged.

    “The role of microglia deficits in neurological development disorders in a mouse model has emerged [154].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [154] Zhan, 2014, Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior, Nat. Neurosci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most serotonin is produced in the GI tract and can be metabolized directly by the gut microbiota; it modulates neurodevelopment and might be important in social function and repetitive behavior.

    “Although most serotonin, or 5′-HT, is produced in the GI tract and can also be metabolized directly by the gut microbiota, it modulates neurodevelopment and might be important in social function and repetitive behavior [188].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [188] Muller, 2016, The serotonin system in autism spectrum disorder: From biomarker to animal models, Neuroscience source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    There is a bidirectional influence between microbiota and diet through the production of metabolites, which can be characterized through metabolomics and can help delineate new therapeutic strategies in autistic patients.

    “This picture shows how there is a bidirectional influence between microbiota and diet, through the production of metabolites, which can be characterized through metabolomics and can help to delineate new therapeutical strategies in autistic patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Propionate modulates 5-HT secretion in the gut and depletes 5-HT and dopamine levels in the brain, which could contribute to hyperserotonemia observed in children with ASD.

    “In addition to direct effects on the brain, propionate has been shown to modulate 5-hydroxytryptamine (5’-HT) secretion in the gut and deplete 5’-HT and dopamine levels in the brain, which could potentially contribute to the hyperserotonemia observed in children with ASD [182,183,184].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [182] Reigstad, 2015, Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells, FASEB J. source

      Not checked in the free run.

    • cites [183] 2014, Relative abundance of short chain and polyunsaturated fatty acids in propionic acid-induced autistic features in rat pups as potential markers in autism, Lipids Health Dis. source

      Not checked in the free run.

    • cites [184] Al-Ghamdi, M., Al-Ayadhi, L., and El-Ansary, A. (2014). Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid—Induced neurotoxicity in rodent model of autism. BMC Neurosci., 15. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In ASD, abnormal intestinal permeability could allow 5-HT to translocate into the systemic circulation, leading to elevated levels of blood 5-HT.

    “In ASD, abnormal intestinal permeability could allow 5′-HT to translocate into the systemic circulation, leading to elevated levels of blood 5′-HT [34,35,127,193].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [34] Celli, 1996, Abnormal intestinal permeability in children with autism, Acta Paediatr. source

      Not checked in the free run.

    • cites [35] Familiari, 2010, Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives, J. Pediatr. Gastroenterol. Nutr. source

      Not checked in the free run.

    • cites [127] Ibrahim, 2009, Incidence of gastrointestinal symptoms in children with autism: A population-based study, Pediatrics source

      Not checked in the free run.

    • cites [193] Gabriele, 2014, Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis, Eur. Neuropsychopharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    5-HT is elevated in whole blood and platelets in approximately 30% of children with ASD, making it a potential candidate as a biomarker for ASD.

    “5′-HT is elevated in whole blood and platelets in approximately 30% of children with ASD, making it a potential candidate as a biomarker for ASD [193].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [193] Gabriele, 2014, Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis, Eur. Neuropsychopharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The gut microbiota could be involved in higher 5-HT production, identifying 5-HT as a potential pathway through which the gut microbiota and brain communicate in ASD.

    “These data indicate that the gut microbiota could be involved in higher 5′-HT production, thus identifying 5′-HT as a potential pathway through which the gut microbiota and brain communicate in ASD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ASD patients have high levels of free amino acids (FAAs), which are derived from hydrolysis of proteins and peptides; glutamate may be involved in the etiopathogenesis of neurodevelopmental disorders.

    “Furthermore, ASD patients have high level of free amino acids (FAAs) [186], which are derived from hydrolysis of proteins and peptides, like glutamate that may be involved in the etiopathogenesis of neurodevelopmental disorders [187].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [186] Ming, 2012, Metabolic perturbance in autism spectrum disorders: A metabolomics study, J. Proteome Res. source

      Not checked in the free run.

    • cites [187] Shimmura, C., Suda, S., Tsuchiya, K.J., Hashimoto, K., Ohno, K., Matsuzaki, H., Iwata, K., Matsumoto, K., Wakuda, T., and Kameno, Y. (2011). Alteration of plasma glutamate and glutamine levels in children with high-functioning autism. PLoS ONE, 6. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Propionic acid is used as a preservative in the food industry and can induce autistic-like behaviors in rodents.

    “In fact, higher levels of AA and PPA that is used as a preservative in the food industry and can also induce autistic-like behaviors in rodents have been reported in ASD children [177,178].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [177] Peppelenbosch, 2010, Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms, Biochim. Biophys. Acta source

      Not checked in the free run.

    • cites [178] Liu, 2019, Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review, Transl. Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Butyric acid can positively modulate neurotransmitter gene expression and rescue behavioral abnormalities in a mouse model.

    “At the same time, lower levels of BA, that can positively modulates neurotransmitter gene expression and can rescue behavioural abnormalities in mouse model, have been reported in ASD [179].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [179] Kratsman, 2016, Sodium butyrate attenuates social behavior deficits and modifies the transcription of inhibitory/excitatory genes in the frontal cortex of an autism model, Neuropharmacology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High levels of 5-HT may be caused by gastrointestinal 5-HT hypersecretion produced by enterochromaffin cells in the gut, involved in motility and secretion.

    “High levels of 5′HT may be caused by a gastrointestinal 5′HT hypersecretion, produced by the enterochromaffin cells in the gut and it is involved in functions such as motility and secretion [189].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [189] Gheorghe, 2019, Focus on the essentials: Tryptophan metabolism and the microbiome-gut-brain axis, Curr. Opin. Pharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ASD patients seem characterized by elevated SCFA concentrations in stool and serum and increased levels of SCFA-producing bacteria (e.g., Clostridia, Desulfovibrio, and Bacteroides).

    “Moreover, ASD patients seem to be characterized by both elevated levels of SCFA concentrations in stool and serum, and increased level of SCFA-producing bacteria (e.g., Clostridia, Desulfovibrio, and Bacteroides) [29,36,180].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [29] Adams, J.B., Johansen, L.J., Powell, L.D., Quig, D., and Rubin, R.A. (2011). Gastrointestinal flora and gastrointestinal status in children with autism—Comparisons to typical children and correlation with autism severity. BMC Gastroenterol., 11. source

      Not checked in the free run.

    • cites [36] De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D.I., Cristofori, F., Guerzoni, M.E., Gobbetti, M., and Francavilla, R. (2013). Fecal Microbiota and Metabolome of Children with Autism and Pervasive Developmental Disorder Not Otherwise Specified. PLoS ONE, 8. source

      Not checked in the free run.

    • cites [180] Wang, 2012, Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder, Dig. Dis. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Higher levels of 5-HT in children with ASD can be linked to intestinal inflammation and play an important role in intestinal inflammatory responses, indicating a connection between enteric serotonin production and dysbiosis.

    “Lastly, higher levels of 5′-HT in children with ASD can be linked to intestinal inflammation and play an important role in intestinal inflammatory responses [200], so there is a connection between enteric serotonin production and dysbiosis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [200] Bischoff, 2009, Role of serotonin in intestinal inflammation: Knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice, Am. J. Physiol. Gastrointest. Liver Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dysbiosis can decrease the number of amino acids absorbed from the diet and reduce the availability of tryptophan, a precursor for serotonin, creating a vicious cycle.

    “On the other hand, dysbiosis can decrease the number of amino acids that are absorbed from the diet and reduce the availability of tryptophan [201], that is a precursor for a number of metabolites as serotonin, thus creating a vicious cycle.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [201] Kraneveld, 2016, Gut-to-Brain Axis in Autism Spectrum Disorders: Central Role for the Microbiome, Int. Rev. Neurobiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Data show decreased capacity for 5-HT synthesis in children with ASD and reports show worsening in repetitive behaviors after tryptophan depletion.

    “This corresponds to data showing decreased capacity for 5′-HT synthesis in children with ASD as well as to reports showing a worsening in repetitive behaviors in individuals with ASD after tryptophan depletion [191,199].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [191] Chugani, 1999, Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children, Ann. Neurol. source

      Not checked in the free run.

    • cites [199] McDougle, 1996, Effects of tryptophan depletion in drug-free adults with autistic disorder, Arch. Gen. Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Increased levels of 5-HT result in a different modulation of 5-HT metabolism in the host, leading to tryptophan depletion and hyperserotoninemia, which may affect GI symptoms.

    “Increased levels of 5′-HT result in a different modulation of 5′-HT metabolism in the host, leading to tryptophan depletion and hyperserotoninemia, which may affect GI symptoms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    As a consequence, an increase in pro-inflammatory cytokines (e.g., IL-1B, IL-6, IL-8, and IL-12p40) was observed, which are associated with impaired social communication and neurodevelopmental disorders.

    “As a consequence, an increase in pro-inflammatory cytokines (e.g., IL-1B, IL-6, IL-8, and IL-12p40) was observed, which are associated with impaired social communication and neurodevelopmental disorders.”
    Quote in the paperNot a substantial claim
57 of 57

  • The paper relies on this without support.

    Diet induces changes in the intestinal microbiota and in the production of molecules such as short-chain fatty acids (SCFAs).

    “Since the diet induces changes in the intestinal microbiota and in the production of molecules, such as the SCFA, we wanted to investigate the role that nutritional intervention can have on GI microbiota composition and thus on its influence on behavior, GI symptoms and microbiota composition and report which are the beneficial effect on ASD conditions.”

  • The paper relies on this without support.

    Ketogenic diet is associated with higher inflammatory and defective mitochondria risk, and its side effects of constipation and reflux may worsen GI comorbidities in ASD.

    “However, KD is associated with higher inflammatory and defective mitochondria risk and its side effects of constipation and reflux may worsen GI comorbidities in ASD.”
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?

  • A decrease in the abundance of Eubacterium and Enterococcus populations within the gastrointestinal tracts of patients diagnosed with ASD has been observed compared to healthy populations.

    “Furthermore, a decrease in the abundance of Eubacterium and Enterococcus populations within the gastrointestinal tracts of patients diagnosed with ASD has been observed when compared to healthy populations [52,107,109].”

    From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [107]

  • The presence of Staphylococcus, Coprococcus, Lactococcus, and Flavonifractor may be detected in lower quantities in ASD.

    “In addition, the presence of Staphylococcus, Coprococcus, Lactococcus, and Flavonifractor may be detected in lower quantities [8,52,107,111,114,115].”

    From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [107]

  • A decrease in the populations of Akkermansia and Sutterella, with particular emphasis on Akkermansia muciniphila, was observed in healthy controls.

    “Moreover, a decrease in the populations of Akkermansia and Sutterella, with a particular emphasis on Akkermansia muciniphila species, was observed in healthy controls [52,89,107,109,110].”

    From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [107]

  • Scientific research on the genus Prevotella, including the species P. copri, yielded equivocal results.

    “The scientific research on the genus Prevotella, including the species P. copri, yielded equivocal results [102,103,107,110,112,114,115].”

    From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [107]

  • The nature of the alterations underlying gastrointestinal disorders is multifactorial, including genetic, morphophysiological, nutritional, psychological, sociodemographic and environmental factors.

    “As the nature of these alterations is multifactorial, and includes genetical, morphophysiological, nutritional, psychological alterations, as well as sociodemographic and environmental factors, among others”

    From Food Selectivity and Its Implications Associated with Gastrointestinal Disorders in Children with Autism Spectrum Disorders (2022) · cites this paper as [69]

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Authors
Ristori, M. V., Quagliariello, A., Reddel, S., Ianiro, G., Vicari, S., Gasbarrini, A., & Putignani, L.
Affiliations
  • Bambino Gesù Children's Hospital (IT)
  • Università Cattolica del Sacro Cuore (IT)
Corresponding author
  • Gasbarrini, Antonio
  • Putignani, Lorenza
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2019-11-18
Volume
11
Issue
11
Pages
2812
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu11112812
PMC
PMC6893818
OpenAlex
W2985368039
Cited by
214
References
202
Citations by year
2026: 20 · 2025: 35 · 2024: 29 · 2023: 38 · 2022: 48 · 2021: 30 · 2020: 13 · 2019: 1
FWCI
2.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Florence Research (University of Florence) (submittedVersion, other-oa)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
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 › Psychiatry and Mental health › Child Nutrition and Feeding Issues
Keywords
autism spectrum disorder, gastrointestinal symptoms, gut microbiota, dietary intervention, short-chain fatty acids, intestinal permeability, gut-brain axis, dietary factors, picky eating, sensory processing, intestinal infection
MeSH terms
Autism Spectrum Disorder, Gastrointestinal Microbiome, Child, Child Nutritional Physiological Phenomena, Child, Preschool, Diet, Fatty Acids, Volatile, Food Preferences, Gastrointestinal Diseases, Humans, Nutritional Status, Serotonin, Neurotransmitter Agents

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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