The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders

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Immune dysfunction and gastrointestinal inflammation are common in individuals with ASD and contribute to severity of behaviors seen in the disorder.

“Immune dysfunction and gastrointestinal (GI) inflammation are also common in individuals with ASD and contribute to severity of behaviors seen in the disorder [6–8].”

• cites [6] Onore C, Careaga M, Ashwood P. The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun. 2012;26(3):383–92. sourceNot checked yet

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• cites [7] McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014;133(5):872–83. sourceNot checked yet

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• cites [8] Mead J, Ashwood P. Evidence supporting an altered immune response in ASD. Immunol Lett. 2015;163(1):49–55. sourceNot checked yet

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Intervention studies such as fecal microbiota transplant therapies show promise and lend credence to the involvement of the microbiota in ASD.

“Intervention studies such as fecal microbiota transplant therapies show promise and lend credence to the involvement of the microbiota in ASD.”

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The microbiota-gut-brain axis has been extensively studied in animal models, and alterations in microbiota composition alter neurological and behavioral outcomes.

“The microbiota-gut-brain (MGB) axis has been extensively studied in animal models, and it is clear that alterations in the composition of microbiota alter neurological and behavioral outcomes.”

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Several human studies show altered microbiota (dysbiosis) in ASD, but the results are heterogeneous and often contradictory.

“Although there are several studies so far showing altered microbiota (dysbiosis) in ASD, the results are heterogeneous and often contradictory.”

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Germ-free mice experience immune dysfunction and are more susceptible to infections than mice kept in conventional facilities.

“These mice experience immune dysfunction and are more susceptible to infections than mice kept in conventional facilities [13, 15].”

• cites [13] Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157(1):121–41. sourceNot checked yet

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• cites [15] Round JL, Mazmanian SK. The gut microbiome shapes intestinal immune responses during health and disease. Nature reviews. Immunology 2009;9(5):313–323. sourceNot checked yet

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Increased Desulfovibrio and Bacteroides vulgatus were identified in children with ASD and were correlated to autism severity.

“Increased Desulfovibrio and Bacteroides vulgatus were identified in children with ASD and were correlated to autism severity [50].”

• cites [50] Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, et al. Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe. 2010;16(4):444–53. sourceNot checked yet

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Disrupted barrier function could facilitate translocation of bacterial metabolites and immune mediators from the gut into circulation, which could lead to activation of microglia as seen in an induced dysbiosis mouse model.

“disrupted barrier function could facilitate the translocation of bacterial metabolites and immune mediators from the gut into circulation (Fig. 1), which could lead to activation of microglia as seen in an induced dysbiosis mouse model [40].”

• cites [40] Bruce-Keller AJ, Salbaum JM, Luo M. Blanchard et, Taylor CM, welsh DA, et al. obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry. 2015;77(7):607–15. sourceNot checked yet

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Deficits in germ-free mice can be corrected by colonization with diverse commensal bacteria, but this is age-dependent, suggesting composition and timing of colonization are critical for immune education.

“These deficits can be corrected by colonization with diverse commensal bacteria; however, this has been shown to be age-dependent, suggesting that both composition and timing of colonization are critical for the education of the immune system [16–18].”

• cites [16] Chung H, Pamp SJ, Hill JA, Surana NK, Edelman SM, Troy EB, et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell. 2012;149(7):1578–93. sourceNot checked yet

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• cites [17] El Aidy S, Hooiveld G, Tremaroli V, Backhed F, Kleerebezem M. The gut microbiota and mucosal homeostasis: colonized at birth or at adulthood, does it matter? Gut Microbes 2013;4(2):118–124. sourceNot checked yet

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• cites [18] Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science. 2016;352(6285):539–44. sourceNot checked yet

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The maternal immune activation model is dependent on microbiota that can induce a T helper 17 response; dams lacking certain microbiota could not mount this response, and their offspring did not display ASD-like behaviors.

“Recently, this model has been shown to be dependent on microbiota that can induce a T helper (TH-) 17 response—dams that lacked certain microbiota could not mount this response, and their offspring did not display the ASD-like behaviors [42•, 43••].”

• cites [42•, 43••]Not checked yet

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Microbiota produce neuroactive metabolites including GABA by Lactobacillus and Bifidobacteria, acetylcholine by Lactobacillus, dopamine by Bacillus and Serratia, and norepinephrine by Escherichia and Saccharomyces, which could enter circulation and directly affect neural processes including the brain.

“Microbiota produce other neuroactive metabolites including GABA by Lactobacillus and Bifidobacteria [36], acetylcholine by Lactobacillus, dopamine by Bacillus and Serratia, and norepinephrine by Escherichia and Saccharomyces, which could enter circulation and directly affect neural processes throughout the body, including the brain (Fig. 1) [37].”

• cites [37] Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. BioEssays. 2011;33(8):574–81. sourceNot checked yet

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Parracho et al. confirmed increased Clostridia in stool samples, and its presence highly correlated with GI symptoms in ASD children.

“Using fluorescence in situ hybridization (FISH) techniques to identify bacteria present in stool samples, Parracho et al. confirmed increased Clostridia, and its presence highly correlated with GI symptoms in ASD children [49].”

• cites [49] Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005;54(Pt 10):987–91. sourceNot checked yet

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The gut microbiota play a critical role in the development of the intestinal architecture and mucosal immune system and are important for regulation of the immune system in the gut.

“The gut microbiota play a critical role in the development of the intestinal architecture and mucosal immune system and are particularly important for regulation of the immune system in the gut [reviewed in [13, 14]].”

• cites [13] Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157(1):121–41. sourceNot checked yet

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• cites [14] Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336(6086):1268–73. sourceNot checked yet

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Dysbiosis introduced in conventionally housed adult mice leads to abnormal behaviors, altered barrier functions, and activation of microglia.

“In addition, dysbiosis introduced in conventionally housed adult mice also leads to abnormal behaviors, altered barrier functions, and activation of the microglia, the resident immune cells of the brain [40].”

• cites [40] Bruce-Keller AJ, Salbaum JM, Luo M. Blanchard et, Taylor CM, welsh DA, et al. obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry. 2015;77(7):607–15. sourceNot checked yet

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Stress in early life can induce dysbiosis and influence immune responses, as shown in maternal separation models of stress.

“Conversely, stress in early life can induce dysbiosis and influence immune responses, as shown in maternal separation models of stress [32].”

• cites [32] O'Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho AM, Quigley EM, et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 2009;65(3):263–7. sourceNot checked yet

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In Shank3 knockout mice, differences were seen specifically in males, with significant alterations in GABA receptor gene expression that could be modulated with Lactobacillus reuteri.

“The latter study saw differences specifically in males, with significant alterations in GABA receptor gene expression in the Shank3 KO mice that could be modulated with the introduction of the probiotic Lactobacillus reuteri [45].”

• cites [45] Tabouy L, Getselter D, Ziv O, Karpuj M, Tabouy T, Lukic I, et al. Dysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders. In: Brain Behav Immun; 2018.Not checked yet

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The gut microbiota can influence brain function and lead to changes in behaviors, as shown extensively in animal models.

“The gut microbiota can influence brain function and lead to changes in behaviors, as shown extensively in animal models [22•].”

• cites [22•]Not checked yet

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Dysbiosis and impaired intestinal barrier function were seen in a maternal immune activation model of autism, with improvements in ASD-relevant behavior after treatment with Bacteroides fragilis.

“Dysbiosis and impaired intestinal barrier function were seen in a maternal immune activation (MIA) model of autism, with improvements in ASD relevant behavior after treatment with Bacteriodes fragilis [41].”

• cites [41] Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155(7):1451–63. sourceNot checked yet

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In germ-free mice, the architecture of the mesenteric lymph nodes and Peyer's patches is smaller and disorganized, with reduced maturation of isolated lymphoid follicles and fewer immune cells.

“In germ-free (GF) mice, the architecture of the mesenteric lymph nodes and Peyers patches is smaller and disorganized, with reduced maturation of isolated lymphoid follicles and fewer numbers of immune cells present.”

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One culture-based study showed significant presence of Candida species in the feces of children with ASD, the majority Candida albicans, and fluconazole-resistant species including C. krusei and C. glabrata were also found.

“So far, fungal microbiota studies in ASD are scant; however, one culture-based study showed significant presence of Candida species in the feces of children with ASD, the majority of which were Candida albicans. Fluconozole-resistant species were also found in significant numbers of cultures, including C. krusei and C. glabrata [96].”

• cites [96] Kantarcioglu AS, Kiraz N, Aydin A. Microbiota-gut-brain Axis: yeast species isolated from stool samples of children with suspected or diagnosed autism Spectrum disorders and in vitro susceptibility against nystatin and fluconazole. Mycopathologia. 2016;181(1–2):1–7. sourceNot checked yet

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A separate study found Candida present in nearly 60% of ASD samples, with none present in controls, and identified hyphae formation suggesting the yeast had switched to its invasive and adhesive form.

“A separate study found Candida present in nearly 60% of ASD samples, with none present in controls. They also identified hyphae formation, suggesting that the dimorphic yeast had switched to its invasive and adhesive form [97].”

• cites [97] Iovene MR, Bombace F, Maresca R, Sapone A, Iardino P, Picardi A, et al. Intestinal Dysbiosis and yeast isolation in stool of subjects with autism Spectrum disorders. Mycopathologia. 2017;182(3–4):349–63. sourceNot checked yet

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Children with ASD are known to have feeding problems, food sensitivities or aversions, and extremely restricted diets, which could contribute to differences in microbiota but not to an ASD diagnosis.

“Children with ASD are known to have feeding problems, food sensitivities/aversions, and extremely restricted diets [89], which could also be contributing to differences in microbiota but not to an ASD diagnosis.”

• cites [89] Cermak SA, Curtin C, Bandini LG. Food selectivity and sensory sensitivity in children with autism spectrum disorders. J Am Diet Assoc. 2010;110(2):238–46. sourceNot checked yet

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In animal models of ASD, elevations of microbial metabolite 4-ethylphenylsulfate correlated with altered behaviors in mice, and probiotic therapy reduced its concentration and improved behaviors in the MIA model.

“In animal models of ASD, elevations of microbial metabolite 4-ethylphenylsulfate (4EPS) correlated with altered behaviors in mice, and probiotic therapy reduced its concentration and improved behaviors in MIA model of ASD [41].”

• cites [41] Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155(7):1451–63. sourceNot checked yet

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A preliminary study of 22 children with ASD and GI dysfunction found that D-arabinitol concentrations and D-arabinitol/L-arabinitol ratios were significantly reduced with daily probiotics, and improvements were seen in certain ASD behaviors including ability to concentrate.

“A preliminary study of 22 children with ASD and GI dysfunction found that DA concentrations and DA/LA ratios were significantly reduced with daily administration of probiotics, and improvements were seen in certain ASD behaviors including ability to concentrate [62].”

• cites [62] Kaluzna-Czaplinska J, Blaszczyk S. The level of arabinitol in autistic children after probiotic therapy. Nutrition (Burbank, Los Angeles County, Calif) 2012;28(2):124–6. sourceNot checked yet

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A large recent study of 40 ASD children (36 severe) and 40 typically developing controls found decreased abundance of Alistipes, Bilophila, Dialister, Parabacteroides, and Veillonella families but increased Collinsella, Corynebacterium, Dorea, and Lactobacillus.

“One of the largest of recent studies that looked at 40 ASD (36 severe) and 40 typically developing control children found decreased abundance of the Alistipes, Bilophila, Dialister, Parabacteroides, and Veillonella families but increased Collinsella, Corynebacterium, Dorea, and Lactobacillus, suggesting major changes in the microbiota composition in ASD.”

• cites [78] Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J, et al. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome. 2017;5(1):24. sourceNot checked yet

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Immune activation may be responsible for the elevation of quinolinic acid in ASD, as activated macrophages and microglia are the main producers of quinolinic acid.

“Immune activation may be responsible for this elevation, as activated macrophages and microglia are the main producers of QA [106].”

• cites [106] Guillemin GJ, Smith DG, Smythe GA, Armati PJ, Brew BJ. Expression of the kynurenine pathway enzymes in human microglia and macrophages. Adv Exp Med Biol. 2003;527:105–12. sourceNot checked yet

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Increases in an alternative branch of the kynurenine pathway led to reduced kynurenic acid and elevated quinolinic acid, an excitotoxic NMDA receptor agonist, in children with ASD.

“Increases in an alternative branch of the kynurenine pathway led to reduced kynurenic acid and elevated quinolinic acid (QA), a compound known to be an excitotoxic N-methyl-D-aspartate (NMDA) receptor agonist, in children with ASD [68] (Fig. 1).”

• cites [68] Gevi F, Zolla L, Gabriele S, Persico AM. Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism. Molecular Autism. 2016;7:47. sourceNot checked yet

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Short-chain fatty acids influence gene expression epigenetically through histone deacetylase inhibition; butyrate-producing bacteria promote peripheral regulatory T cell expansion, altering gut immunity by promoting tolerance, through increased acetylation at the Foxp3 promoter and expansion of CD4+ Foxp3+ Tregs.

“SCFA influence gene expression epigenetically through histone deacetylase (HDAC) inhibition. For example, butyrate-producing bacteria promote peripheral regulatory T cell (Tregs) expansion, altering gut immunity by promoting tolerance. This occurs through HDAC inhibition leading to increased acetylation at the Foxp3 promotor and expansion of CD4+ Foxp3+ Tregs [102••].”

• cites [102••]Not checked yet

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The composition of microbiota is very sensitive to changes in diet, fiber composition, and other factors, and can also be altered by stress and other compounding factors.

“Note that the composition of microbiota is very sensitive to changes diet, fiber composition, etc., and can also be altered by stress and other compounding factors [10].”

• cites [10] RodrÍguez JM, Murphy K, Stanton C, Ross RP, Kober OI, Juge N, et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015;26(1):26050.Not checked yet

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Serotonin plays important neurotrophic roles during early development, and elevations of 5-HT during critical time periods can alter cognition and sensory processing.

“Serotonin plays important neurotrophic roles during early development, and elevations of 5-HT during critical time periods can alter cognition and sensory processing [109].”

• cites [109] Miceli S, Negwer M, van Eijs F, Kalkhoven C, van Lierop I, Homberg J, et al. High serotonin levels during brain development alter the structural input-output connectivity of neural networks in the rat somatosensory layer IV. Front Cell Neurosci. 2013;7:88. sourceNot checked yet

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Altered patterns of bacterial metabolites were seen in a large number of children with ASD compared to healthy controls, including elevated HPHPA, a catabolic byproduct of Clostridia.

“Altered patterns of bacterial metabolites were seen in a large number of children with ASD compared to healthy control children. These metabolites included elevated 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), a catabolic byproduct of Clostridia [59].”

• cites [59] Shaw W. Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia. Nutr Neurosci. 2010;13(3):135–43. sourceNot checked yet

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Metabolome studies have repeatedly shown evidence of alterations in tryptophan, kynurenine, and serotonin pathways in children with ASD, including increased urinary excretion of tryptophan and associated metabolites.

“Metabolome studies have repeatedly shown evidence of alterations in tryptophan, kynurenine, and serotonin pathways in children with ASD, including reports of increased urinary excretion of tryptophan and associated metabolites [63, 67, 68, 72, 105].”

• cites [63] Ming X, Stein TP, Barnes V, Rhodes N, Guo L. Metabolic perturbance in autism spectrum disorders: a metabolomics study. J Proteome Res. 2012;11(12):5856–62. sourceNot checked yet

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• cites [67] Noto A, Fanos V, Barberini L, Grapov D, Fattuoni C, Zaffanello M, et al. The urinary metabolomics profile of an Italian autistic children population and their unaffected siblings. J Matern Fetal Neonatal Med. 2014;27(sup2):46–52. sourceNot checked yet

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• cites [68] Gevi F, Zolla L, Gabriele S, Persico AM. Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism. Molecular Autism. 2016;7:47. sourceNot checked yet

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• cites [72] Lussu M, Noto A, Masili A, Rinaldi AC, Dessì A, De Angelis M, et al. The urinary 1H-NMR metabolomics profile of an italian autistic children population and their unaffected siblings. Autism Res. 2017;10(6):1058–66. sourceNot checked yet

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• cites [105] Diémé B, Mavel S, Blasco H, Tripi G, Bonnet-Brilhault F, Malvy J, et al. Metabolomics study of urine in autism Spectrum disorders using a multiplatform analytical methodology. J Proteome Res. 2015;14(12):5273–82. sourceNot checked yet

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Several studies found lower levels of fecal short-chain fatty acids, including butyrate, in feces of ASD children, while a 2012 study found increased ammonia and short-chain fatty acids including acetic, butyric, isobutyric, valeric, and isovaleric acids in ASD.

“Several studies found lower levels of fecal SCFA, including butyrate in feces of ASD children [53, 64], while a 2012 study found increased ammonia and SCFA including acetic, butyric, isobutyric, valeric, and isovaleric acids in ASD [61].”

• cites [53] Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011;11:22. sourceNot checked yet

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• cites [64] De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One 2013;8. sourceNot checked yet

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The majority of the fibers of the vagus nerve are afferent sensory fibers, delivering sensory information from the periphery, including the GI tract, to the brain.

“The majority of the fibers of the vagus nerve are afferent sensory fibers, delivering sensory information from the periphery, including the GI tract, to the brain [110].”

• cites [110] Bonaz B, Bazin T, Pellissier S. The Vagus nerve at the Interface of the microbiota-gut-brain Axis. Front Neurosci. 2018;12:49. sourceNot checked yet

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Some short-chain fatty acids such as propionic acid can be neurotoxic in higher concentrations and have been shown to cause behavioral abnormalities in rodent models.

“some SCFAs such as propionic acid (PPA) can be neurotoxic in higher concentrations and have been shown to cause behavioral abnormalities in rodent models [100, 101]”

• cites [100] Shultz SR, MacFabe DF, Ossenkopp KP, Scratch S, Whelan J, Taylor R, et al. Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: implications for an animal model of autism. Neuropharmacology. 2008;54(6):901–11. sourceNot checked yet

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• cites [101] MacFabe DF, Cain NE, Boon F, Ossenkopp KP, Cain DP. Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: relevance to autism spectrum disorder. Behav Brain Res. 2011;217(1):47–54. sourceNot checked yet

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Neural communication between the brain and the microbiota may occur through direct pattern recognition sensing due to Toll-like receptor expression on afferent fibers.

“It is understood that neural communication between the brain and the microbiota may be occurring indirectly through hormones or neurotransmitter release by gut endocrine cells in presence of the microbiota and metabolites, or perhaps through direct pattern recognition sensing due to Toll-like receptor expression on afferent fibers [110].”

• cites [110] Bonaz B, Bazin T, Pellissier S. The Vagus nerve at the Interface of the microbiota-gut-brain Axis. Front Neurosci. 2018;12:49. sourceNot checked yet

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Some studies found increased diversity of microbiota in ASD, whereas other studies show decreased diversity and richness or no differences in diversity.

“Some studies found increased diversity of the microbiota in ASD [47, 64], whereas other studies show the opposite trend towards decreased diversity and richness [73, 74], or no differences in diversity [75, 77].”

• cites [47] Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML, Bolte E, et al. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis. 2002;35(Suppl 1):S6–s16. sourceNot checked yet

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• cites [64] De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One 2013;8. sourceNot checked yet

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The gut microbiota are critical for regulating tryptophan metabolism, either directly by degrading tryptophan to indole derivatives or indirectly through mammalian kynurenine and serotonin pathways.

“The gut microbiota are critical for regulating Trp metabolism, either directly by degrading Trp to indole-derivatives or indirectly through mammalian kynurenine and serotonin pathways.”

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Germ-free mouse models have shown that the serotonergic system in the brain is influenced by the microbiota, whereby excess peripheral tryptophan may cross the blood-brain barrier to influence the rate of serotonin synthesis in the brain.

“GF mouse models have shown that the serotonergic system in the brain is also influenced by the microbiota [24, 26], whereby excess peripheral Trp may cross the BBB to influence the rate serotonin synthesis in the brain [108].”

• cites [24] Neufeld KM, Kang N, Bienenstock J, Foster JA. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil. 2011;23(3):255–64 e119. sourceNot checked yet

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• cites [26] Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F, et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry. 2013;18(6):666–73. sourceNot checked yet

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Shifts in short-chain fatty acid production could potentially contribute to altered immune regulation in the gut and lead to peripheral inflammation.

“Therefore, shifts in SCFA production could potentially contribute to altered immune regulation in the gut and lead to peripheral inflammation (Fig. 1).”

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There is no consensus for differences in microbiota in ASD, and a meta-analysis of 15 studies could not amalgamate the often contradictory results.

“Overall, there does not seem to be consensus for differences in microbiota in ASD, and a meta-analysis of 15 studies could not amalgamate the often contradictory results [87].”

• cites [87] Cao X, Lin P, Jiang P, Li C. Characteristics of the gastrointestinal microbiome in children with autism spectrum disorder: a systematic review. Shanghai Arch Psychiatry. 2013;25(6):342–53.Not checked yet

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P-cresol, a microbial metabolite produced by Clostridium species, was significantly elevated in children with ASD, especially females with severe autism.

“P-cresol, another microbial metabolite produced by Clostridium species, was significantly elevated in children with ASD, especially females with severe autism [60].”

• cites [60] Altieri L, Neri C, Sacco R, Curatolo P, Benvenuto A, Muratori F, et al. Urinary p-cresol is elevated in small children with severe autism spectrum disorder. Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals. Biomarkers 2011;16(3):252–60. sourceNot checked yet

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A recent clinical trial involving fecal microbiota transplant in 18 ASD children led to significantly improved GI symptoms and ASD-relevant behaviors, with increases in Bifidobacterium, Prevotella, and Desulfovibrio, and these changes persisted at the 8-week follow-up.

“A recent clinical trial which involved fecal microbiota transplant (FMT) in 18 ASD children led to significantly improved GI symptoms and ASD-relevant behaviors, with increases in Bifidobacterium, Prevotella, and Desulfovibrio. These changes persisted at the 8-week follow-up [79•].”

• cites [79•]Not checked yet

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Dysbiotic microbiota, their influence on the immune system, and their metabolic byproducts contribute directly to the development of these disorders.

“Reports that behaviors improve after modification of the microbiota support the hypothesis that dysbiotic microbiota, their influence on the immune system, and their metabolic byproducts contribute directly to the development of these disorders.”