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

In the paper

“Actually, at our knowledge, no studies have reported the effect of MD on ASD patients.”

In the paper

“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.”

What the sources say

• Not checked yetcites [62] Schmitt, 2008, A Comparison of Nutrient Intake and Eating Behaviors of Boys with and Without Autism, Top. Clin. Nutr. source
• Not checked yetcites [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 yetcites [72] Emond, 2010, Feeding symptoms, dietary patterns, and growth in young children with autism spectrum disorders, Pediatrics source
• Not checked yetcites [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 yetcites [74] Levy, 2007, Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders, Biol. Psychiatry source

In the paper

“From a nutritional point of view this leads to an inadequate caloric intake and hence to nutritional deficits [49,50].”

What the sources say

• Not checked yetcites [49] Markham, 2010, Feeding and eating disorders in childhood, Int. J. Eat. Disord. source
• Not checked yetcites [50] Kreipe, 2012, Beyond picky eating: Avoidant/restrictive food intake disorder, Curr. Psychiatry Rep. source

In the paper

“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].”

What the sources say

• Not checked yetcites [58] Berry, 2015, Nutrition Management of Gastrointestinal Symptoms in Children with Autism Spectrum Disorder: Guideline from an Expert Panel, J. Acad. Nutr. Diet. source

In the paper

“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].”

What the sources say

• Not checked yetcites [52] Williams, 2000, Eating habits of children with autism, Pediatr. Nurs.
• Not checked yetcites [53] Schreck, 2006, Food preferences and factors influencing food selectivity for children with autism spectrum disorders, Res. Dev. Disabil. source
• Not checked yetcites [54] Klein, 1999, Characteristics of patients with autistic disorder (AD) presenting for dental treatment: A survey and chart review, Spec. Care Dentist. source
• Not checked yetcites [55] Zazpe, 2014, Food selectivity in autism spectrum disorders: A systematic review, J. Child Neurol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [60] Nadon, 2011, Mealtime problems in children with autism spectrum disorder and their typically developing siblings: A comparison study, Autism source

In the paper

“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].”

What the sources say

• Not checked yetcites [26] Horvath, 2002, Autistic disorder and gastrointestinal disease, Curr. Opin. Pediatr. source
• Not checked yetcites [27] Cermak, 2010, Food Selectivity and Sensory Sensitivity in Children with Autism Spectrum Disorders, J. Am. Diet. Assoc. source

In the paper

“Protein intake was adequate or quite similar to that of typically developing children [69,72,73,74,75,76,77].”

What the sources say

• Not checked yetcites [69] Zimmer, 2012, Food variety as a predictor of nutritional status among children with autism, J. Autism Dev. Disord. source
• Not checked yetcites [72] Emond, 2010, Feeding symptoms, dietary patterns, and growth in young children with autism spectrum disorders, Pediatrics source
• Not checked yetcites [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 yetcites [74] Levy, 2007, Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders, Biol. Psychiatry source
• Not checked yetcites [75] Xia, 2010, A preliminary study on nutritional status and intake in Chinese children with autism, Eur. J. Pediatr. source
• Not checked yetcites [76] Johnson, 2008, Eating habits and dietary status in young children with autism, J. Dev. Phys. Disabil. source
• Not checked yetcites [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

In the paper

“A strong preference for starches, snacks and processed foods, along with a rejection of fruits, vegetables or protein, is particularly common [56,57].”

What the sources say

• Not checked yetcites [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
• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [34] Celli, 1996, Abnormal intestinal permeability in children with autism, Acta Paediatr. source
• Not checked yetcites [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 yetcites [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 yetcites [37] Finegold, 2010, Pyrosequencing study of fecal microflora of autistic and control children, Anaerobe source
• Not checked yetcites [38] Mulle, 2013, The Gut Microbiome: A New Frontier in Autism Research, Curr. Psychiatry Rep. source
• Not checked yetcites [39] Parracho, 2005, Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children, J. Med. Microbiol. source
• Not checked yetcites [40] Wang, 2011, Normal gut microbiota modulates brain development and behavior, Proc. Natl. Acad. Sci. USA source
• Not checked yetcites [41] Elsden, 1976, The end products of the metabolism of aromatic amino acids by Clostridia, Arch. Microbiol. source
• Not checked yetcites [42] Finegold, 2002, Gastrointestinal microflora studies in late-onset autism, Clin. Infect. Dis. source
• Not checked yetcites [43] Selmer, 2001, p-Hydroxyphenylacetate decarboxylase from Clostridium difficile. A novel glycyl radical enzyme catalysing the formation of p-cresol, Eur. J. Biochem. source

In the paper

“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.”

In the paper

“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].”

What the sources say

• Not checked yetcites [76] Johnson, 2008, Eating habits and dietary status in young children with autism, J. Dev. Phys. Disabil. source
• Not checked yetcites [78] Evans, 2012, Dietary Patterns and Body Mass Index in Children with Autism and Typically Developing Children, Res. Autism Spectr. Disord. source
• Not checked yetcites [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 yetcites [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 yetcites [79] Bicer, 2013, Body mass index, dietary intake and feeding problems of Turkish children with autism spectrum disorder (ASD), Res. Dev. Disabil. source
• Not checked yetcites [80] Hyman, 2012, Nutrient intake from food in children with autism, Pediatrics source

In the paper

“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].”

What the sources say

• Not checked yetcites [84] Castro, 2015, Effect of a ketogenic diet on autism spectrum disorder: A systematic review, Res. Autism Spectr. Disord. source

In the paper

“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].”

What the sources say

• Not checked yetcites [84] Castro, 2015, Effect of a ketogenic diet on autism spectrum disorder: A systematic review, Res. Autism Spectr. Disord. source
• Not checked yetcites [107] Evangeliou, 2003, Application of a ketogenic diet in children with autistic behavior: Pilot study, J. Child Neurol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [85] Hediger, 2008, Reduced bone cortical thickness in boys with autism or autism spectrum disorder, J. Autism Dev. Disord. source
• Not checked yetcites [86] Neumeyer, 2015, Brief report: Bone fractures in children and adults with autism spectrum disorders, J. Autism Dev. Disord. source
• Not checked yetcites [87] Clark, 1993, Symptomatic vitamin A and D deficiencies in an eight-year-old with autism, J. Parenter. Enter. Nutr. source
• Not checked yetcites [88] Stewart, 2008, Symptomatic nutritional rickets in a teenager with autistic spectrum disorder, Child Care Health Dev. source

In the paper

“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].”

What the sources say

• Not checked yetcites [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
• Not checked yetcites [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
• Not checked yetcites [102] Nadal, 2009, Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects, Br. J. Nutr. source

In the paper

“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]”

What the sources say

• Not checked yetcites [105] Reichelt, 2009, The possibility and probability of a gut-to-brain connection in autism, Ann. Clin. Psychiatry
• Not checked yetcites [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

In the paper

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

In the paper

“Excessive consumption of sodium was reported [79,84], probably due to the consumption of packaged foods.”

What the sources say

• Not checked yetcites [79] Bicer, 2013, Body mass index, dietary intake and feeding problems of Turkish children with autism spectrum disorder (ASD), Res. Dev. Disabil. source
• Not checked yetcites [84] Castro, 2015, Effect of a ketogenic diet on autism spectrum disorder: A systematic review, Res. Autism Spectr. Disord. source

In the paper

“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].”

What the sources say

• Not checked yetcites [37] Finegold, 2010, Pyrosequencing study of fecal microflora of autistic and control children, Anaerobe source
• Not checked yetcites [39] Parracho, 2005, Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children, J. Med. Microbiol. source
• Not checked yetcites [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 yetcites [145] Tomova, 2015, Gastrointestinal microbiota in children with autism in Slovakia, Physiol. Behav. source

In the paper

“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.”

What the sources say

• Not checked yetcites [123] Alda, 2017, The Mediterranean Diet and ADHD in Children and Adolescents, Pediatrics source

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [127] Ibrahim, 2009, Incidence of gastrointestinal symptoms in children with autism: A population-based study, Pediatrics source

In the paper

“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]”

What the sources say

• Not checked yetcites [19] Obrenovich, 2011, Altered heavy metals and transketolase found in autistic spectrum disorder, Biol. Trace Elem. Res. source
• Not checked yetcites [20] Splawski, 2006, CACNA1H mutations in autism spectrum disorders, J. Biol. Chem. source

In the paper

“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].”

What the sources say

• Not checked yetcites [111] Haas, 1955, The treatment of celiac disease with the specific carbohydrate diet; report on 191 additional cases, Am. J. Gastroenterol.
• Not checked yetcites [112] Gottschall, 2004, Digestion-gut-autism connection: The Specific Carbohydrate Diet, Med. Veritas J. Med. Truth source
• Not checked yetcites [113] Suskind, 2014, Nutritional therapy in pediatric Crohn disease: The specific carbohydrate diet, J. Pediatr. Gastroenterol. Nutr. source
• Not checked yetcites [114] Obih, 2016, Specific carbohydrate diet for pediatric inflammatory bowel disease in clinical practice within an academic IBD center, Nutrition source

In the paper

“This was the first study showing that low adherence to the MD is associated with odds of an ADHD diagnosis in children and adolescents.”

What the sources say

• Not checked yetcites [123] Alda, 2017, The Mediterranean Diet and ADHD in Children and Adolescents, Pediatrics source

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [109] Mychasiuk, 2017, Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder, Autism Res. source

In the paper

“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].”

What the sources say

• Not checked yetcites [112] Gottschall, 2004, Digestion-gut-autism connection: The Specific Carbohydrate Diet, Med. Veritas J. Med. Truth source

In the paper

“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].”

What the sources say

• Not checked yetcites [127] Ibrahim, 2009, Incidence of gastrointestinal symptoms in children with autism: A population-based study, Pediatrics source

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [176] MacFabe, 2015, Enteric short-chain fatty acids: Microbial messengers of metabolism, mitochondria, and mind: Implications in autism spectrum disorders, Microb. Ecol. Health Dis.

In the paper

“Others studies observed, in ASD children, high abundance of: Akkermansia muciniphilia, [36,143,148] Desulfovibrio, [37] and Faecalibacterium prausnitzii [36].”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [148] Xu, 2019, Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis, Front. Psychiatry source
• Not checked yetcites [37] Finegold, 2010, Pyrosequencing study of fecal microflora of autistic and control children, Anaerobe source

In the paper

“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].”

What the sources say

• Not checked yetcites [174] Byrne, 2015, The role of short chain fatty acids in appetite regulation and energy homeostasis, Int. J. Obes. source

In the paper

“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].”

What the sources say

• Not checked yetcites [144] Hsiao, 2013, Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders, Cell source

In the paper

“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].”

What the sources say

• Not checked yetcites [149] Strati, 2017, New evidences on the altered gut microbiota in autism spectrum disorders, Microbiome source

In the paper

“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].”

What the sources say

• Not checked yetcites [151] Qin, 2007, Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration, Glia source

In the paper

“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].”

What the sources say

• Not checked yetcites [166] Desbonnet, 2015, Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour, Brain Behav. Immun. source

In the paper

“Candida spp., Streptococcus spp., Escherichia spp. and Enterococcus spp. produce serotonin;”

What the sources say

• Not checked yetcites [172] Dinan, 2013, Melancholic microbes: A link between gut microbiota and depression?, Neurogastroenterol. Motil. source

In the paper

“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].”

What the sources say

• Not checked yetcites [156] Wang, 2014, The role of microbiome in central nervous system disorders, Brain Behav. Immun. source

In the paper

“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].”

What the sources say

• Not checked yetcites [155] Trevarthen, 2006, Collaborative Regulations of Vitality in Early Childhood: Stress in Intimate Relationships and Postnatal Psychopathology, Developmental Psychopathology

In the paper

“The role of microglia deficits in neurological development disorders in a mouse model has emerged [154].”

What the sources say

• Not checked yetcites [154] Zhan, 2014, Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior, Nat. Neurosci. source

In the paper

“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].”

What the sources say

• Not checked yetcites [188] Muller, 2016, The serotonin system in autism spectrum disorder: From biomarker to animal models, Neuroscience source

In the paper

“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.”

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [34] Celli, 1996, Abnormal intestinal permeability in children with autism, Acta Paediatr. source
• Not checked yetcites [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 yetcites [127] Ibrahim, 2009, Incidence of gastrointestinal symptoms in children with autism: A population-based study, Pediatrics source
• Not checked yetcites [193] Gabriele, 2014, Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis, Eur. Neuropsychopharmacol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [193] Gabriele, 2014, Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis, Eur. Neuropsychopharmacol. source

In the paper

“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.”

In the paper

“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].”

What the sources say

• Not checked yetcites [186] Ming, 2012, Metabolic perturbance in autism spectrum disorders: A metabolomics study, J. Proteome Res. source
• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [177] Peppelenbosch, 2010, Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms, Biochim. Biophys. Acta source
• Not checked yetcites [178] Liu, 2019, Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review, Transl. Psychiatry source

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [189] Gheorghe, 2019, Focus on the essentials: Tryptophan metabolism and the microbiome-gut-brain axis, Curr. Opin. Pharmacol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [180] Wang, 2012, Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder, Dig. Dis. Sci. source

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [201] Kraneveld, 2016, Gut-to-Brain Axis in Autism Spectrum Disorders: Central Role for the Microbiome, Int. Rev. Neurobiol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [191] Chugani, 1999, Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children, Ann. Neurol. source
• Not checked yetcites [199] McDougle, 1996, Effects of tryptophan depletion in drug-free adults with autistic disorder, Arch. Gen. Psychiatry source

In the paper

“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.”

In the paper

“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.”