Unraveling the Connections: Eating Issues, Microbiome, and Gastrointestinal Symptoms in Autism Spectrum Disorder

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ASD is associated with a high prevalence of eating disorders, gastrointestinal symptoms, and alterations in gut microbiota composition.

“While the core features of ASD are well-established, there is increasing recognition of the presence of feeding disorders, gastrointestinal issues, and changes in gut microbiota among affected individuals [4].”

• cites [4] Viviers, 2020, Parent-Reported Feeding and Swallowing Difficulties of Children with Autism Spectrum Disorders (Aged 3 to 5 Years) Compared to Typically Developing Peers: A South African Study, Afr. Health Sci. sourceNot checked yet

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Compared to individuals with anorexia nervosa or bulimia nervosa, patients with ARFID tend to be younger, are more likely to be male, and are often diagnosed with co-occurring psychiatric and/or medical issues.

“Research has shown that, in comparison to individuals with AN or BN, patients with ARFID tend to be younger, are more likely to be male, and are often diagnosed with co-occurring psychiatric and/or medical issues [24].”

• cites [24] Nicely, 2014, Prevalence and Characteristics of Avoidant/Restrictive Food Intake Disorder in a Cohort of Young Patients in Day Treatment for Eating Disorders, J. Eat. Disord. sourceNot checked yet

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Food neophobia in the neurotypical population leads to lower BMI, whereas when combined with ASD it leads to higher BMI.

“Interestingly, the paper shows that FN in the NT population leads to lower Body Mass Index (BMI), whereas when combined with ASD, it leads to higher BMI.”

• cites [20] Wallace, 2018, Autism Spectrum Disorder and Food Neophobia: Clinical and Subclinical Links, Am. J. Clin. Nutr. sourceNot checked yet

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The prevalence of ARFID in the general pediatric population is approximately 3.2% based on self-reported data from primary school children.

“In contrast, the prevalence of ARFID in the general pediatric population is significantly lower, estimated at approximately 3.2% based on self-reported data from primary school children [28].”

• cites [28] Kurz, 2015, Early-Onset Restrictive Eating Disturbances in Primary School Boys and Girls, Eur. Child. Adolesc. Psychiatry sourceNot checked yet

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Current data suggest a link between gastrointestinal problems in ASD and the microbiota, but the amount of evidence is limited.

“Current data suggest a link between gastrointestinal problems in ASD and the microbiota, but the amount of evidence is limited.”

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Suarez et al. found sensory over-responsivity was significantly linked to food selectivity, with the relationship persisting over two years; increased SOR predicted more severe food selectivity, but repetitive behaviors were not an independent predictor.

“Using a custom SOR questionnaire and the Repetitive Behaviors Scale–Revised (RBS-R) for repetitive behaviors (RRB), they found that SOR was significantly linked to FS, with this relationship persisting over two years. Increased SOR also predicted more severe FS, but RRB was not an independent predictor, suggesting a strong correlation between SOR and RRB.”

• cites [43] Suarez, 2014, Longitudinal Follow-up of Factors Associated with Food Selectivity in Children with Autism Spectrum Disorders, Autism sourceNot checked yet

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• cites [44] Suarez, 2012, Associations of Physiological Factors, Age, and Sensory Over-Responsivity with Food Selectivity in Children with Autism Spectrum Disorders, Open J. Occup. Ther. sourceNot checked yet

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Children with ARFID have increased abundance of potentially pathogenic bacteria such as Enterobacterales and Bacteroidaceae including Bacteroides vulgatus, and a significant reduction in beneficial Bifidobacterium species.

“There is an increased abundance of potentially pathogenic bacteria such as Enterobacterales and Bacteroidaceae—including species like Bacteroides vulgatus—and a significant reduction in beneficial Bifidobacterium species.”

• cites [36] Ye, Q., Sun, S., Deng, J., Chen, X., Zhang, J., Lin, S., Du, H., Gao, J., Zou, X., and Lin, X. (2023). Using 16S rDNA and Metagenomic Sequencing Technology to Analyze the Fecal Microbiome of Children with Avoidant/Restrictive Food Intake Disorder. Sci. Rep., 13. sourceNot checked yet

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Children with ASD are approximately five times more likely to experience feeding problems than children without ASD.

“Additionally, research indicates a significant disparity in feeding problems between children with and without ASD, with those in the former group being approximately five times more likely to experience such issues [6].”

• cites [6] 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. sourceNot checked yet

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The dysbiotic state in ARFID suggests an imbalance between harmful and beneficial bacteria, potentially affecting the gut-brain axis.

“This dysbiotic state suggests an imbalance between harmful and beneficial bacteria, potentially affecting the gut–brain axis (further expanded below in Section 9 and Section 10) [36].”

• cites [36] Ye, Q., Sun, S., Deng, J., Chen, X., Zhang, J., Lin, S., Du, H., Gao, J., Zou, X., and Lin, X. (2023). Using 16S rDNA and Metagenomic Sequencing Technology to Analyze the Fecal Microbiome of Children with Avoidant/Restrictive Food Intake Disorder. Sci. Rep., 13. sourceNot checked yet

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

Common gastrointestinal symptoms in ASD include constipation, abdominal pain, and diarrhea.

“Common gastrointestinal symptoms include constipation, abdominal pain, and diarrhea [5].”

• cites [5] Deng, W., Wang, S., Li, F., Wang, F., Xing, Y.P., Li, Y., Lv, Y., Ke, H., Li, Z., and Lv, P.J. (2022). Gastrointestinal Symptoms Have a Minor Impact on Autism Spectrum Disorder and Associations with Gut Microbiota and Short-Chain Fatty Acids. Front. Microbiol., 13. sourceNot checked yet

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In gastrointestinal problems associated with ASD, a vicious cycle may play a significant role: ASD symptoms contribute to ARFID prevalence, which leads to microbiota degradation, ultimately worsening ASD symptoms.

“In gastrointestinal problems associated with ASD, a ‘vicious cycle’ may play a significant role: ASD symptoms contribute to the prevalence of ARFID, which in turn leads to microbiota degradation, ultimately worsening ASD symptoms.”

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Evans et al. found lower consumption of fruits and vegetables in the ASD group compared to typically developing children, and autistic children displayed a preference for snack foods and dairy-free sweetened soft drinks.

“The findings of a study by Evans et al. also indicated a lower consumption of fruits and vegetables in the ASD group compared to typically developing children. Contrary to findings in the above-mentioned study, autistic children displayed a preference for snack foods and dairy-free sweetened soft drinks [50].”

• cites [50] Evans, 2012, Dietary Patterns and Body Mass Index in Children with Autism and Typically Developing Children, Res. Autism Spectr. Disord. sourceNot checked yet

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In a Swedish twin study of 16,951 twin pairs aged 6 to 12 years, ARFID had high heritability, with genetic factors significantly contributing and non-shared environmental factors playing a smaller yet significant role.

“In a comprehensive, nationwide study conducted in Sweden involving 16,951 twin pairs aged 6 to 12 years, findings revealed a high heritability for ARFID, indicating that genetic factors significantly contribute to the disorder’s development. Additionally, the study found that non-shared environmental factors played a smaller yet significant role [25].”

• cites [25] Dinkler, 2023, Etiology of the Broad Avoidant Restrictive Food Intake Disorder Phenotype in Swedish Twins Aged 6 to 12 Years, JAMA Psychiatry sourceNot checked yet

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Plaza-Diaz et al. found lower intake of fruits and vegetables in ASD children; high fat and high energy foods including juices, snack foods, confectionery, and baked goods characterized dietary choices; increased dairy consumption was associated with greater intake of cereals and pasta; children had lower consumption of lean meat and eggs with excessive intake of fatty meats.

“A lower intake of fruits and vegetables was reported in the ASD children. Foods of high fat and high energy content, including juices, snack foods, confectionery, and baked goods, characterized the subjects’ dietary choices. Additionally, an increase in dairy consumption was associated with a greater intake of cereals and pasta. Children exhibited lower consumption of lean meat and eggs, with”

• cites [51] Plaza-Diaz, J., Flores-Rojas, K., de la Torre-Aguilar, M.J., Gomez-Fernández, A.R., Martín-Borreguero, P., Perez-Navero, J.L., Gil, A., and Gil-Campos, M. (2021). Dietary Patterns, Eating Behavior, and Nutrient Intakes of Spanish Preschool Children with Autism Spectrum Disorders. Nutrients, 13. sourceNot checked yet

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The prevalence of ARFID in the general population is estimated to be between 0.5% and 5%.

“The prevalence of ARFID in the general population is not well established, but estimates suggest it may affect between 0.5% and 5% of people [23].”

• cites [23] Kennedy, 2022, How Genetic Analysis May Contribute to the Understanding of Avoidant/Restrictive Food Intake Disorder (ARFID), J. Eat. Disord. sourceNot checked yet

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Sharp et al. found 78% of 70 ASD children omitted one or more food groups, most often vegetables (67.1%).

“Similarly, Sharp et al. found that 78% of 70 ASD children omitted one or more food groups, most often vegetables (67.1%) [15].”

• cites [15] Sharp, 2018, Dietary Intake, Nutrient Status, and Growth Parameters in Children with Autism Spectrum Disorder and Severe Food Selectivity: An Electronic Medical Record Review, J. Acad. Nutr. Diet. sourceNot checked yet

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At six months of age, parents of children with ASD reported challenges with introduction of solid foods and described their children as slow eaters; children consumed less fruit and vegetables, sweets, and carbonated beverages; no differences were observed in weight, height, or BMI at 18 months and seven years.

“At six months of age, parents reported challenges with the introduction of solid foods and described their children as “slow eaters”. Additionally, children consumed less fruit and vegetables, sweets, and carbonated beverages. However, no differences were observed in weight, height, or BMI at 18 months and seven years between the ASD patients and the control group [49].”

• cites [49] Emond, 2010, Feeding Symptoms, Dietary Patterns, and Growth in Young Children with Autism Spectrum Disorders, Pediatrics sourceNot checked yet

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Children with ASD often struggle to eat in various settings, with over half experiencing difficulties dining at regular restaurants and at friends' homes.

“A study by Provost et al. found that children with ASD often struggle to eat in various settings, with over half experiencing difficulties dining at regular restaurants and facing challenges when eating at friends’ homes [12].”

• cites [12] Provost, 2010, Mealtime Behaviors of Preschool Children: Comparison of Children with Autism Spectrum Disorder and Children with Typical Development, Phys. Occup. Ther. Pediatr. sourceNot checked yet

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Feeding abnormalities in individuals with ASD can begin early in life, even during breastfeeding, with common challenges including disorganized and vigorous sucking that continues despite satiation.

“Feeding abnormalities in individuals with ASD can begin early in life, even during breastfeeding. Common challenges during this period include disorganized and vigorous sucking that continues despite the child being satiated [11].”

• cites [11] Lucas, 2015, Dysregulated Breastfeeding Behaviors in Children Later Diagnosed with Autism, J. Perinat. Educ. sourceNot checked yet

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These eating challenges often result in limited dietary variety, persistent nutritional deficiencies, and social difficulties, with sensory sensitivities playing a critical role.

“These challenges often result in a limited dietary variety, persistent nutritional deficiencies, and social difficulties, with sensory sensitivities playing a critical role.”

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Hubbard et al. report ASD children often reject food based on texture or consistency and when ingredients are combined, while these factors are less significant for neurotypical children.

“Similarly, Hubbard et al. report that ASD children often reject food based on texture or consistency and when ingredients are combined, while these factors are less significant for NT children [41].”

• cites [41] Hubbard, 2014, A Comparison of Food Refusal Related to Characteristics of Food in Children with Autism Spectrum Disorder and Typically Developing Children, J. Acad. Nutr. Diet. sourceNot checked yet

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Emond et al. found individuals with ASD had feeding difficulties from infancy and less diversified diets from the age of 15 months.

“A questionnaire study conducted by Emond et al. indicated that individuals with ASD exhibited feeding difficulties from infancy and had diets that were less diversified from the age of 15 months.”

• cites [49] Emond, 2010, Feeding Symptoms, Dietary Patterns, and Growth in Young Children with Autism Spectrum Disorders, Pediatrics sourceNot checked yet

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ASD-diagnosed children were introduced to complementary foods at a later stage, demonstrated lower acceptance, and had longer periods of bottle-feeding.

“Furthermore, ASD-diagnosed children were introduced to complementary foods at a later stage and demonstrated a lower acceptance rate. This resulted in longer periods of bottle-feeding [48].”

• cites [48] Xiang, X., Yang, T., Chen, J., Chen, L., Dai, Y., Zhang, J., Li, L., Jia, F., Wu, L., and Hao, Y. (2023). Association of Feeding Patterns in Infancy with Later Autism Symptoms and Neurodevelopment: A National Multicentre Survey. BMC Psychiatry, 23. sourceNot checked yet

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Germ-free mice prefer to spend more time in isolation rather than interacting with other mice; colonizing these mice with pathogen-free gut microbiota increased sociability but did not affect social novelty.

“Desbonnet et al. documented that germ-free (GF) mice prefer to spend more time in isolation rather than interacting with other mice. They also showed that colonizing these mice with pathogen-free gut microbiota increased sociability but did not affect social novelty [108].”

• cites [108] Desbonnet, 2014, Microbiota Is Essential for Social Development in the Mouse, Mol. Psychiatry sourceNot checked yet

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• AssumptionRests on an assumption: Findings from animal models about microbiota–gut–brain interactions can be generalized to human ASD.

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Analysis of the ARFID group revealed alterations in gut bacterial composition following two patterns: an increase in potentially harmful bacteria and a decrease in beneficial ones.

“Analysis of the ARFID group revealed alterations in their gut bacterial composition. These changes followed two concerning patterns: an increase in potentially harmful bacteria and a decrease in beneficial ones.”

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

Research findings on the characteristic gut microbiota composition in individuals with ASD remain inconsistent, with studies often reporting contradictory results regarding specific bacterial species.

“Research findings on the characteristic gut microbiota composition in individuals with ASD remain inconsistent, with studies often reporting contradictory results regarding specific bacterial species.”

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Diolordi et al. found a statistically significant reduction in milk and yogurt consumption among children with ASD compared to controls, and a marked decrease in vegetable intake, with 41% of ASD children never consuming vegetables versus 6.9% of typically developing children.

“The study by Diolordi et al. identified a statistically significant reduction in milk and yogurt consumption among children with ASD compared to the control group. Additionally, researchers noted a marked decrease in vegetable intake within the ASD group, with 41% of children (mean age 58.3 months) never consuming vegetables, in contrast to only 6.9% of TD children.”

• cites [54] Diolordi, 2014, Eating Habits and Dietary Patterns in Children with Autism, Eat. Weight. Disord. sourceNot checked yet

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In BTBR mice, serum and intestinal contents showed decreased 5-amino valeric acid and taurine, weak GABA receptor agonists; administering 5AV and taurine improved social behavior and reduced repetitive behaviors.

“Analyses of serum and intestinal contents showed decreased amounts of 5-amino valeric acid (5AV) and taurine, weak gamma-aminobutyric acid (GABA) receptor agonists. Administering 5AV and taurine to BTBR mice improved their social behavior and reduced repetitive behaviors [114].”

• cites [114] Sharon, 2019, Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice, Cell sourceNot checked yet

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• AssumptionRests on an assumption: Findings from animal models about microbiota–gut–brain interactions can be generalized to human ASD.

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In offspring of mice treated with poly(I:C), there are alterations in gut microbiota composition and increased levels of 4-ethylphenylsulfate, which can induce anxiety-like behaviors.

“In offspring of mice treated with poly(I:C), there are alterations in the composition of the gut microbiota, as well as increased levels of the microbial metabolite 4-ethylphenylsulfate (4EPS), which can induce anxiety-like behaviors [115].”

• cites [115] Hsiao, 2013, Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders, Cell sourceNot checked yet

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• AssumptionRests on an assumption: Findings from animal models about microbiota–gut–brain interactions can be generalized to human ASD.

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Children with ASD typically have a restricted and selective diet, often including limited fruits and vegetables, high-calorie snacks, processed foods, carbohydrate-rich items, reduced dairy, preferred dairy-free soft drinks and sweetened fruit juices, and limited protein.

“Children with Autism Spectrum Disorder typically have a restricted and selective diet. Studies indicate that their diet often includes limited fruits and vegetables. Commonly consumed foods include high-calorie snacks, processed foods, and carbohydrate-rich items such as pasta, pizza, biscuits, and white bread. Dairy intake is reduced with lower milk and yogurt consumption, while dairy-free soft”

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Among patients with ASD, gastrointestinal symptoms are frequently reported as more prevalent and severe, with occurrence varying from 9% to 84% compared to 9-37% in children without ASD.

“Among patients with ASD, gastrointestinal (GI) symptoms are frequently reported as more prevalent and severe. The occurrence of GI symptoms among children with ASD varies widely across studies, ranging from 9% to 84%, compared to 9–37% in children without ASD [70].”

• cites [70] Wasilewska, 2015, Gastrointestinal Symptoms and Autism Spectrum Disorder: Links and Risks—A Possible New Overlap Syndrome, Pediatr. Health Med. Ther. sourceNot checked yet

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Children with ASD face increased risk of overweight and obesity, attributed to preferences for calorie-dense foods high in carbohydrates, simple sugars, and fats.

“At the same time, they face an increased risk of overweight and obesity, attributed to preferences for calorie-dense foods high in carbohydrates, simple sugars, and fats [65].”

• cites [65] Kahathuduwa, 2019, The Risk of Overweight and Obesity in Children with Autism Spectrum Disorders: A Systematic Review and Meta-Analysis, Obes. Rev. sourceNot checked yet

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Enterobacteriaceae are well-known for pathogenic associations.

“The increased bacteria included members of the Enterobacteriaceae family, which are well-known for their pathogenic associations [118].”

• cites [118] Janda, 2021, The Changing Face of the Family Enterobacteriaceae (Order: “Enterobacterales”): New Members, Taxonomic Issues, Geographic Expansion, and New Diseases and Disease Syndromes, Clin. Microbiol. Rev. sourceNot checked yet

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Plaza-Diaz et al. found higher energy density and elevated saturated fats, calcium, and vitamin C, while showing deficiencies in iron, iodine, and B vitamins such as riboflavin and folic acid.

“In the study mentioned above by Plaza-Diaz et al., the research group was characterized by higher energy density and elevated levels of saturated fats, calcium, and vitamin C, while showing deficiencies in iron, iodine, and B vitamins (such as riboflavin and folic acid) [51].”

• cites [51] Plaza-Diaz, J., Flores-Rojas, K., de la Torre-Aguilar, M.J., Gomez-Fernández, A.R., Martín-Borreguero, P., Perez-Navero, J.L., Gil, A., and Gil-Campos, M. (2021). Dietary Patterns, Eating Behavior, and Nutrient Intakes of Spanish Preschool Children with Autism Spectrum Disorders. Nutrients, 13. sourceNot checked yet

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A significantly lower intake of fruits and vegetables reduces fiber consumption, and combined with insufficient fluid intake, may hinder healthy intestinal transit and increase the likelihood of constipation.

“A significantly lower intake of fruits and vegetables reduces fiber consumption, and combined with insufficient fluid intake, may hinder healthy intestinal transit and increase the likelihood of constipation [75].”

• cites [75] Ofei, 2018, Constipation Burden in Children with Autism Spectrum Disorder: Emergency Department and Healthcare Use, J. Pediatr. sourceNot checked yet

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Neophobia reduces microbial diversity in the intestines, and this decreased diversity is hypothesized to contribute to gastrointestinal symptoms such as abdominal pain and irregular stool consistency.

“Neophobia reduces microbial diversity in the intestines. This decreased diversity is hypothesized to contribute to gastrointestinal symptoms such as abdominal pain and irregular stool consistency, ranging from loose to hard stools [73].”

• cites [73] Ristori, M.V., Quagliariello, A., Reddel, S., Ianiro, G., Vicari, S., Gasbarrini, A., and Putignani, L. (2019). Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions. Nutrients, 11. sourceNot checked yet

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Supplementation of maternal immune activation offspring with Bacteroides fragilis corrected defects in gut permeability, reduced anxiety-like and stereotypic behavior, and decreased levels of 4EPS.

“Supplementation of MIA offspring with the human commensal Bacteroides fragilis corrected defects in gut permeability, reduced anxiety-like and stereotypic behavior, as well as decreased levels of 4EPS [115].”

• cites [115] Hsiao, 2013, Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders, Cell sourceNot checked yet

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• AssumptionRests on an assumption: Findings from animal models about microbiota–gut–brain interactions can be generalized to human ASD.

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In a Turkish study, 58.5% of sampled children with ASD were overweight or obese, and 11% were thin or severely thin.

“A study conducted in Turkey revealed that the majority of the sampled children exhibited either overweight or obesity (58.5%). Furthermore, 11% of the children were classified as thin (3rd–15th percentile) or severely thin (<3rd percentile) [59].”

• cites [59] Bicer, 2013, Body Mass Index, Dietary Intake and Feeding Problems of Turkish Children with Autism Spectrum Disorder (ASD), Res. Dev. Disabil. sourceNot checked yet

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Offspring of mice fed a high-fat diet during pregnancy showed ASD-like social symptoms; introducing L. reuteri improved social deficits.

“Offspring of mice that were fed with a high-fat diet (HFD) during pregnancy showed ASD-like social symptoms. Introducing certain bacteria, such as L. reuteri, improved social deficits in these mice [110].”

• cites [110] Buffington, 2016, Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring, Cell sourceNot checked yet

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• AssumptionRests on an assumption: Findings from animal models about microbiota–gut–brain interactions can be generalized to human ASD.

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Xu et al.'s meta-analysis of 9 studies concluded that participants with ASD had lower amounts of Akkermansia, Bacteroides, Bifidobacterium, Escherichia coli, and Enterococcus and higher quantities of Faecalibacterium and Lactobacillus, with a slight increase in Ruminococcus and Clostridium.

“They concluded that participants with ASD had lower amounts of Akkermansia, Bacteroides, Bifidobacterium, Escherichia coli, and Enterococcus and higher quantities of Faecalibacterium and Lactobacillus. There was also a slight increase in the abundance of Ruminococcus and Clostridium [106].”

• cites [106] Xu, M., Xu, X., Li, J., and Li, F. (2019). Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Front. Psychiatry, 10. sourceNot checked yet

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

Gastrointestinal disturbances affect up to 70% of children with ASD, making them one of the most prevalent problems of this condition.

“Gastrointestinal disturbances affect up to 70% of children with ASD, making them one of the most prevalent problems of this condition [100].”

• cites [100] Chaidez, 2014, Gastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development, J. Autism Dev. Disord. sourceNot checked yet

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US nationally representative data indicate obesity prevalence in children with ASD was 30.4%, compared to 23.6% in children without autism.

“The results of a study based on US nationally representative data indicate that the prevalence of obesity in children with ASD was 30.4%, compared to 23.6% of children without autism [66].”

• cites [66] 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. sourceNot checked yet

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A larger meta-analysis of 18 studies confirmed increased Faecalibacterium and decreased Bifidobacterium in ASD children, showed higher Bacteroides contrary to Xu et al., identified three predominant bacterial phyla (Bacteroidetes, Firmicutes, Actinobacteria), and found increased Parabacteroides, Clostridium, and Phascolarctobacterium along with reduced Coprococcus.

“While this study confirmed the increased abundance of Faecalibacterium and decreased levels of Bifidobacterium in ASD children, it showed higher levels of Bacteroides—contrary to Xu et al.’s findings. The study also identified three predominant bacterial phyla in ASD children (Bacteroidetes, Firmicutes, and Actinobacteria) and found increased levels of Parabacteroides, Clostridium, and Phascolarct”

• cites [107] Iglesias-Vázquez, L., Van Ginkel Riba, G., Arija, V., and Canals, J. (2020). Composition of Gut Microbiota in Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Nutrients, 12. sourceNot checked yet

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Children with ASD are particularly vulnerable to being underweight, often due to reduced caloric intake from selective food rejection.

“Children with ASD are particularly vulnerable to being underweight, often due to reduced caloric intake from selective food rejection [64].”

• cites [64] Kittana, M., Ahmadani, A., Williams, K.E., and Attlee, A. (2023). Nutritional Status and Feeding Behavior of Children with Autism Spectrum Disorder in the Middle East and North Africa Region: A Systematic Review. Nutrients, 15. sourceNot checked yet

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ASD symptoms can contribute to the development of ARFID, which leads to microbiota degradation, further exacerbating ASD symptoms and creating a self-reinforcing loop.

“This creates a cycle—ASD symptoms can contribute to the development of ARFID, which leads to microbiota degradation, further exacerbating ASD symptoms and creating a self-reinforcing loop.”

• AssumptionRests on an assumption: Individuals with ASD experience food selectivity and ARFID significantly more often than the neurotypical population.
• AssumptionRests on an assumption: ASD symptoms contribute to the development of ARFID.

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Dysbiosis leads to decreased maturity and function of microglia in a mouse model, contributing to neuroinflammation associated with ASD.

“Dysbiosis leads to decreased maturity and function of microglia in a mouse model [144], contributing to neuroinflammation associated with ASD [98].”

• cites [144] Thion, 2018, Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner, Cell sourceNot checked yet

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• cites [98] Yuan, 2019, Inflammation-Related Biomarkers in Major Psychiatric Disorders: A Cross-Disorder Assessment of Reproducibility and Specificity in 43 Meta-Analyses, Transl. Psychiatry sourceNot checked yet

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In a mouse model of ASD induced by maternal Poly(I:C), alterations in gut microbiota composition and increased levels of microbial 4EPS are observed in offspring, which can induce anxiety-like behaviors.

“In a mouse model of ASD induced by maternal Poly(I:C), alterations in gut microbiota composition and increased levels of the microbial 4EPS are observed in offspring, which can induce anxiety-like behaviors.”

• cites [115] Hsiao, 2013, Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders, Cell sourceNot checked yet

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The interaction between inflammatory responses and oxidative stress can amplify oxidative damage, creating negative feedback that disrupts brain development and functioning and potentially contributes to neurodevelopmental disorders like ASD.

“This interaction can amplify oxidative damage, creating negative feedback that disrupts brain development and functioning and potentially contributes to the development of neurodevelopmental disorders like ASD.”

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The ketogenic diet has limited evidence suggesting it may reduce bacterial dysbiosis and promote BDNF levels.

“The ketogenic diet (KD), on the other hand, has limited evidence suggesting it may reduce bacterial dysbiosis and promote BDNF levels, as noted by Allan et al. [171].”

• cites [171] Allan, N.P., Yamamoto, B.Y., Kunihiro, B.P., Nunokawa, C.K.L., Rubas, N.C., Wells, R.K., Umeda, L., Phankitnirundorn, K., Torres, A., and Peres, R. (2024). Ketogenic Diet Induced Shifts in the Gut Microbiome Associate with Changes to Inflammatory Cytokines and Brain-Related miRNAs in Children with Autism Spectrum Disorder. Nutrients, 16. sourceNot checked yet

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Enteroendocrine cells produce serotonin, GLP-1, and PYY, which affect brain function and behavior.

“These cells produce serotonin, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY), affecting brain function and behavior [89,90,136].”

• cites [89] Bloom, 2012, Gut Hormones and Appetite Control: A Focus on PYY and GLP-1 as Therapeutic Targets in Obesity, Gut Liver sourceNot checked yet

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• cites [90] Richards, 2014, Identification and Characterization of GLP-1 Receptor-Expressing Cells Using a New Transgenic Mouse Model, Diabetes sourceNot checked yet

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• cites [136] Donovan, M.H., and Tecott, L.H. (2013). Serotonin and the Regulation of Mammalian Energy Balance. Front. Neurosci., 7. sourceNot checked yet

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These nutrients may support neurological and gastrointestinal health, helping improve food tolerance and potentially alleviate sensory sensitivities and food neophobia.

“These nutrients may support neurological and gastrointestinal health, helping to improve food tolerance and potentially alleviate sensory sensitivities and food neophobia [170].”

• cites [170] Pérez-Cabral, I.D., Bernal-Mercado, A.T., Islas-Rubio, A.R., Suárez-Jiménez, G.M., Robles-García, M.Á., Puebla-Duarte, A.L., and Del-Toro-Sánchez, C.L. (2024). Exploring Dietary Interventions in Autism Spectrum Disorder. Foods, 13. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

A restrictive diet in ASD may impact brain function through the gut-brain-microbiota axis, creating a self-perpetuating cycle of gastrointestinal and behavioral challenges.

“This, in turn, may impact brain function through the gut–brain–microbiota axis, creating a self-perpetuating cycle of gastrointestinal and behavioral challenges.”

• AssumptionRests on an assumption: Sensory oversensitivity in individuals with ASD often leads to restrictive diets.

May combine two claims.

Gut-produced serotonin cannot cross the blood-brain barrier but influences mood and social behavior through peripheral systems.

“While gut-produced serotonin cannot cross the blood–brain barrier, it influences mood and social behavior through peripheral systems [136,137,138,139,140].”

• cites [136] Donovan, M.H., and Tecott, L.H. (2013). Serotonin and the Regulation of Mammalian Energy Balance. Front. Neurosci., 7. sourceNot checked yet

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• cites [137] Wang, 2023, The Microbiota-Gut-Brain Axis and Neurodevelopmental Disorders, Protein Cell sourceNot checked yet

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• cites [138] Reigstad, 2015, Gut Microbes Promote Colonic Serotonin Production through an Effect of Short-Chain Fatty Acids on Enterochromaffin Cells, FASEB J. sourceNot checked yet

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• cites [139] Yano, 2015, Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis, Cell sourceNot checked yet

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• cites [140] Wopereis, 2014, Altered Gut Microbiota and Activity in a Murine Model of Autism Spectrum Disorders, Brain Behav. Immun. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Increasing butyrate levels may improve social interactions and decrease repetitive behaviors.

“On the contrary, increasing butyrate levels may improve social interactions and decrease repetitive behaviors [146].”

• cites [146] 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 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Germ-free mice present social deficits and spend significantly more time on repetitive behaviors, and are often treated as ASD mouse models.

“GF mice present numerous social deficits, like reluctance towards new relationships and avoiding contact with unknown mice. They spend significantly more time on repetitive behaviors like self-grooming. Hence, they are often treated as ASD mouse models and used to assess intestinal microbiome impact on behavior [124].”

• cites [124] Doifode, 2024, The Many Faces of Microbiota-Gut-Brain Axis in Autism Spectrum Disorder, Life Sci. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Supplementing Poly(I:C) offspring with human commensal Bacteroides fragilis improved gut permeability, reduced anxiety-like and repetitive behaviors, and decreased 4EPS levels.

“Supplementing these offspring with the human commensal Bacteroides fragilis improved gut permeability, reduced anxiety-like and repetitive behaviors, and decreased 4EPS levels [115].”

• cites [115] Hsiao, 2013, Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders, Cell sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Elevated levels of oxidative stress and inflammation are observed in individuals with ASD and are thought to play a key role in the disorder's pathogenesis.

“In the case of the anti-inflammatory diet, its potential relevance stems from the elevated levels of oxidative stress and inflammation observed in individuals with ASD, which are thought to play a key role in the disorder’s pathogenesis [169].”

• cites [169] Usui, N., Kobayashi, H., and Shimada, S. (2023). Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder. Int. J. Mol. Sci., 24. sourceNot checked yet

  Not checked in the free run.

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

The interplay between ASD symptoms, ARFID, and gut dysbiosis highlights the crucial role of the gut-brain axis in neurodevelopmental disorders.

“The interplay between ASD symptoms, ARFID, and gut dysbiosis highlights the crucial role of the gut–brain axis in neurodevelopmental disorders.”

May combine two claims.

A key issue is the heterogeneity of the data, with many studies involving small sample sizes, focusing on specific populations, or relying heavily on parental reports, which can introduce subjective bias and reduce generalizability.

“A key issue is the heterogeneity of the data, with many studies involving small sample sizes, focusing on specific populations (e.g., single ethnicities or regions), or relying heavily on parental reports, which can introduce subjective bias and reduce the generalizability of the results.”

May combine two claims.

ASD is closely linked to dietary selectivity, gastrointestinal dysfunction, and gut microbiota alterations, forming a self-perpetuating cycle that impacts both physical and behavioral health.

“ASD is closely linked to dietary selectivity, gastrointestinal dysfunction, and gut microbiota alterations, forming a self-perpetuating cycle that impacts both physical and behavioral health.”

May combine two claims.

During KD, increased ketone bodies like β-hydroxybutyrate can cross the BBB and may have neuroprotective effects resulting in behavioral improvement in children with ASD.

“During KD, there is an increased level of ketone bodies, like β-hydroxybutyrate, which can cross the BBB and may have neuroprotective effects resulting in behavioral improvement in children with ASD.”

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

More research is needed before such data can be used as formal guidelines.

“However, more research is needed before such data can be used as formal guidelines.”

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

Both reviews highlight the significant role of dietary selectivity in shaping gut microbiota and its potential implications for gastrointestinal and behavioral symptoms.

“Both reviews highlight the significant role of dietary selectivity in shaping gut microbiota and its potential implications for gastrointestinal and behavioral symptoms.”

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

Schneider et al.'s conceptual model of the microbiota-gut-brain axis provides insights into how restrictive eating behaviors can influence gut microbiota diversity and, in turn, affect psychological and physiological processes.

“Schneider et al. [182] have addressed a related topic within the context of ARFID. Their conceptual model of the microbiota–gut–brain axis provides valuable insights into how restrictive eating behaviors can influence gut microbiota diversity and, in turn, affect psychological and physiological processes.”

• cites [182] Schneider, 2024, A Role for the Microbiota-Gut-Brain Axis in Avoidant/Restrictive Food Intake Disorder: A New Conceptual Model, Int. J. Eat. Disord. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

ASD-specific factors, such as heightened sensory sensitivities, distinguish the challenges faced by this population; these sensitivities often lead to selective eating patterns that exacerbate nutritional deficiencies and uniquely impact gut microbiota composition.

“However, ASD-specific factors, such as heightened sensory sensitivities, distinguish the challenges faced by this population. These sensitivities often lead to selective eating patterns that exacerbate nutritional deficiencies and uniquely impact gut microbiota composition.”

• AssumptionRests on an assumption: Sensory oversensitivity in individuals with ASD often leads to restrictive diets.

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

Evidence suggests that dietary interventions, probiotics, and behavioral strategies can improve symptoms, but further research is needed to establish standardized therapeutic approaches.

“While evidence suggests that dietary interventions, probiotics, and behavioral strategies can improve symptoms, further research is needed to establish standardized therapeutic approaches.”

May combine two claims.

Engaging in regular physical exercise can help alleviate challenges in ASD by enhancing motor skills, improving social interactions, and reducing anxiety and behavioral problems.

“Engaging in regular physical exercise can help alleviate these challenges by enhancing motor skills, improving social interactions, and reducing anxiety and behavioral problems [178].”

• cites [178] Jia, S., Guo, C., Li, S., Zhou, X., Wang, X., and Wang, Q. (2023). The Effect of Physical Exercise on Disordered Social Communication in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front. Pediatr., 11. sourceNot checked yet

  Not checked in the free run.

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

Regular physical activity is essential for individuals with ASD as it enhances physical health and improves behavioral outcomes.

“Regular physical activity is essential for individuals with ASD as it not only enhances physical health but also improves behavioral outcomes [177].”

• cites [177] Koh, S.H. (2024). Analyzing the Influence of Physical Exercise Interventions on Social Skills in Children with Autism Spectrum Disorder: Insights from Meta-Analysis. Front. Psychol., 15. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The probiotic studies were limited by small sample sizes and a lack of analysis of baseline gut microbiota composition.

“Despite these promising results, the studies were limited by small sample sizes and a lack of analysis of baseline gut microbiota composition [176].”

• cites [176] Liu, Y.-W., Liong, M.T., Chung, Y.-C.E., Huang, H.-Y., Peng, W.-S., Cheng, Y.-F., Lin, Y.-S., Wu, Y.-Y., and Tsai, Y.-C. (2019). Effects of Lactobacillus Plantarum PS128 on Children with Autism Spectrum Disorder in Taiwan: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 11. sourceNot checked yet

  Not checked in the free run.

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

Much of the mechanistic understanding is derived from animal models, which may not fully translate to human conditions.

“Additionally, much of the mechanistic understanding is derived from animal models, which may not fully translate to human conditions.”

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

Overall, there is increasing evidence supporting the role of dietary interventions in improving gastrointestinal symptoms in children with ASD.

“Overall, there is increasing evidence supporting the role of dietary interventions in improving gastrointestinal symptoms in children with ASD.”

May combine two claims.

Longer probiotic treatments demonstrated significant benefits in reducing irritability, stereotyped behaviors, and hyperactivity.

“Longer treatments, however, demonstrated significant benefits in reducing irritability, stereotyped behaviors, and hyperactivity.”

• cites [176] Liu, Y.-W., Liong, M.T., Chung, Y.-C.E., Huang, H.-Y., Peng, W.-S., Cheng, Y.-F., Lin, Y.-S., Wu, Y.-Y., and Tsai, Y.-C. (2019). Effects of Lactobacillus Plantarum PS128 on Children with Autism Spectrum Disorder in Taiwan: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 11. sourceNot checked yet

  Not checked in the free run.

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

Our review lacks a systematic approach, which impacts the robustness of the findings.

“Our review faces several limitations, most notably the lack of a systematic approach, which impacts the robustness of the findings.”

May combine two claims.

Variability in microbiota analysis techniques and reliance on parental observations introduce biases related to family dynamics and reporting accuracy, hindering comparability and synthesis of results.

“The variability in microbiota analysis techniques and reliance on parental observations further introduce biases related to family dynamics and reporting accuracy, hindering comparability and synthesis of results.”

May combine two claims.

The KD demonstrated a positive effect on gut microbiota, enhancing diversity and promoting a more balanced composition.

“The KD demonstrated a positive effect on gut microbiota, enhancing diversity and promoting a more balanced composition.”

• cites [171] Allan, N.P., Yamamoto, B.Y., Kunihiro, B.P., Nunokawa, C.K.L., Rubas, N.C., Wells, R.K., Umeda, L., Phankitnirundorn, K., Torres, A., and Peres, R. (2024). Ketogenic Diet Induced Shifts in the Gut Microbiome Associate with Changes to Inflammatory Cytokines and Brain-Related miRNAs in Children with Autism Spectrum Disorder. Nutrients, 16. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Rare complications of the ketogenic diet include pancreatitis, prolonged QT intervals, and transient vascular changes.

“Rare complications, such as pancreatitis, prolonged QT intervals, and transient vascular changes, have also been reported.”

• cites [172] Santangelo, A., Corsello, A., Spolidoro, G.C., Trovato, C.M., Agostoni, C., Orsini, A., Milani, G.P., and Peroni, D.G. (2023). The Influence of Ketogenic Diet on Gut Microbiota: Potential Benefits, Risks and Indications. Nutrients, 15. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

There is insufficient evidence on the long-term effects of the ketogenic diet, and no current studies conclusively support its recommendation.

“Additionally, there is insufficient evidence on the long-term effects of this diet, and no current studies conclusively support its recommendation.”

May combine two claims.

These results indicate improved gut health and a reduction in the pathogenic potential of gut microbes.

“These results indicate improved gut health and a reduction in the pathogenic potential of gut microbes.”

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

These microbial communities are integral to production of substances such as SCFAs, which have key neurobiological roles in the microbiota-gut-brain axis, and 4-ethylphenylsulfate, a tyrosine metabolite implicated in ASD-like behaviors.

“These microbial communities are integral to the production of substances such as SCFAs, which have key neurobiological roles in the microbiota–gut–brain axis, and 4-ethylphenylsulfate, a tyrosine metabolite implicated in ASD-like behaviors.”

May combine two claims.

Evidence for therapeutic interventions, including dietary modifications and probiotics, remains limited, with long-term effects of ketogenic or anti-inflammatory diets still unclear.

“Evidence for therapeutic interventions, including dietary modifications and probiotics, remains limited, with the long-term effects of approaches such as ketogenic or anti-inflammatory diets still unclear.”

May combine two claims.

In ASD, gut microbial composition is significantly altered, with differences in the Firmicutes-to-Bacteroidetes ratio and reduced levels of Fusobacteria and Verrucomicrobia compared to neurotypical children.

“In ASD, the gut microbial composition is significantly altered, with differences in the Firmicutes-to-Bacteroidetes ratio and reduced levels of Fusobacteria and Verrucomicrobia compared to neurotypical children.”

Classified as probably not a substantial claim.

Modulating the gut microbiome with psychobiotics offers a promising therapeutic approach for ASD.

“Kwak et al. suggest that modulating the gut microbiome with psychobiotics—probiotics known to positively affect neurological function and hold potential for treating psychiatric conditions—offers a promising therapeutic approach for ASD [175].”

• cites [175] Kwak, M.-J., Kim, S.H., Kim, H.H., Tanpure, R., Kim, J.I., Jeon, B.-H., and Park, H.-K. (2023). Psychobiotics and Fecal Microbial Transplantation for Autism and Attention-Deficit/Hyperactivity Disorder: Microbiome Modulation and Therapeutic Mechanisms. Front. Cell Infect. Microbiol., 13. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Probiotic intake has been shown to benefit health by promoting positive changes in gut microbiota, and studies suggest probiotic interventions in children with ASD may be a valuable complementary therapy for symptom relief.

“Probiotic intake has been shown to benefit health by promoting positive changes in gut microbiota, and studies suggest that probiotic interventions in children with ASD may be a valuable complementary therapy for symptom relief [173,174].”

• cites [173] Sivamaruthi, B.S., Suganthy, N., Kesika, P., and Chaiyasut, C. (2020). The Role of Microbiome, Dietary Supplements, and Probiotics in Autism Spectrum Disorder. Int. J. Environ. Res. Public Health, 17. sourceNot checked yet

  Not checked in the free run.

• cites [174] Ng, Q.X., Loke, W., Venkatanarayanan, N., Lim, D.Y., Soh, A.Y.S., and Yeo, W.S. (2019). A Systematic Review of the Role of Prebiotics and Probiotics in Autism Spectrum Disorders. Medicina, 55. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Common side effects of the ketogenic diet include hypoglycemia, dyslipidemia, gastrointestinal symptoms, carnitine deficiency, bone conditions (osteopenia, osteoporosis), nephrolithiasis, and growth delays, requiring close supervision in pediatric cases.

“Common issues include hypoglycemia, dyslipidemia, gastrointestinal symptoms, carnitine deficiency, bone conditions (e.g., osteopenia, osteoporosis), nephrolithiasis, and growth delays, requiring close supervision in pediatric cases.”

• cites [172] Santangelo, A., Corsello, A., Spolidoro, G.C., Trovato, C.M., Agostoni, C., Orsini, A., Milani, G.P., and Peroni, D.G. (2023). The Influence of Ketogenic Diet on Gut Microbiota: Potential Benefits, Risks and Indications. Nutrients, 15. sourceNot checked yet

  Not checked in the free run.