Microbial products, released into the bloodstreams of mammals including humans, cross the blood-brain barrier and influence neurodevelopment. They can either promote or alleviate neurological disorders including autism spectrum disorders (ASD). This editorial describes how our microbiota influence our feelings, attitudes and mental states with particular reference to ASD.

1.
Balan S, Iwayama Y, Maekawa M, Toyota T, Ohnishi T, Toyoshima M, Shimamoto C, Esaki K, Yamada K, Iwata Y, Suzuki K, Ide M, Ota M, Fukuchi S, Tsujii M, Mori N, Shinkai Y, Yoshikawa T: Exon resequencing of H3K9 methyltransferase complex genes, EHMT1, EHMT2 and WIZ, in Japanese autism subjects. Mol Autism 2014;5:49.
[PubMed]
2.
Bauman MD, Iosif AM, Smith SE, Bregere C, Amaral DG, Patterson PH: Activation of the maternal immune system during pregnancy alters behavioral development of rhesus monkey offspring. Biol Psychiatry 2014;75:332-341.
[PubMed]
3.
Blaster MJ: Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues. New York, Holt & Company, 2014, pp 222-223.
4.
Borody TJ, Warren EF, Leis SM, Surace R, Ashman O, Siarakas S: Bacteriotherapy using fecal flora: toying with human motions. J Clin Gastroenterol 2004;38:475-483.
[PubMed]
5.
Buie T, Fuchs GJ 3rd, Furuta GT, Kooros K, Levy J, Lewis JD, Wershil BK, Winter H: Recommendations for evaluation and treatment of common gastrointestinal problems in children with ASDs. Pediatrics 2010;125(suppl 1):S19-S29.
[PubMed]
6.
Cao Y, Rocha ER, Smith CJ: Efficient utilization of complex N-linked glycans is a selective advantage for Bacterioides fagilis in extraintestinal infections. Proc Natl Acad Sci USA 2014;35:12901-12906.
[PubMed]
7.
Casanova MF, El-Baz A, Elnakib A, Switala AE, Williams EL, Williams DL, Minshew NJ, Conturo TE: Quantitative analysis of the shape of the corpus callosum in patients with autism and comparison individuals. Autism 2011;15:223-238.
[PubMed]
8.
D'Eufemia P, Celli M, Finocchiaro R, Pacifico L, Viozzi L, Zaccagnini M, Cardi E, Giardini O: Abnormal intestinal permeability in children with autism. Acta Paediatr 1996;85:1076-1079.
[PubMed]
9.
Dachtler J, Glasper J, Cohen RN, Ivorra JL, Swiffen DJ, Jackson AJ, Harte MK, Rodgers RJ, Clapcote SJ: Deletion of α-neurexin II results in autism-related behaviors in mice. Transl Psychiatry 2014;4:e484.
[PubMed]
10.
Dash S, Clarke G, Berk M, Jacka FN: The gut microbiome and diet in psychiatry: focus on depression. Curr Opin Psychiatry 2015;28:1-6.
[PubMed]
11.
De Magistris L, Familiari V, Pascotto A, Sapone A, Frolli A, Iardino P, Carteni M, De Rosa M, Francavilla R, Riegler G, Militerni R, Bravaccio C: Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr 2010;51:418-424.
[PubMed]
12.
El-Ansary A, Al-Ayadhi L: Neuroinflammation in autism spectrum disorders. J Neuroinflammation 2012;9:265.
[PubMed]
13.
Ettinger R, MacDonald K, Reid G, Burton JP: The influence of the human microbiome and probiotics on cardiovascular health. Gut Microbes 2014;5:719-728.
[PubMed]
14.
Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, Youn E, Summanen PH, Granpeesheh D, Dixon D, Liu M, Molitoris DR, Green JA 3rd: Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 2010;16:444-453.
[PubMed]
15.
Finegold SM, Downes J, Summanen PH: Microbiology of regressive autism. Anaerobe 2012;18:260-262.
[PubMed]
16.
Fond G, Boukouaci W, Chevalier G, Regnault A, Eberl G, Hamdani N, Dickerson F, Macgregor A, Boyer L, Dargel A, Oliveira J, Tamouza R, Leboyer M: The ‘psychomicrobiotic': targeting microbiota in major psychiatric disorders: a systematic review. Pathol Biol (Paris) 2015;63:35-42.
[PubMed]
17.
Gesundheit B, Rosenzweig JP, Naor D, Lerer B, Zachor DA, Prochazka V, Melamed M, Kristt DA, Steinberg A, Shulman C, Hwang P, Koren G, Walfisch A, Passweg JR, Snowden JA, Tamouza R, Leboyer M, Farge-Bancel D, Ashwood P: Immunological and autoimmune considerations of autism spectrum disorders. J Autoimmun 2013;44:1-7.
[PubMed]
18.
Goines PE, Ashwood P: Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment. Neurotoxicol Teratol 2013;36:67-81.
[PubMed]
19.
Gonzalez H, Elgueta D, Montoya A, Pacheco R: Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases. J Neuroimmunol 2014;274:1-13.
[PubMed]
20.
Gotz J, Ittner LM: Animal models of Alzheimer's disease and frontotemporal dementia. Nat Rev Neurosci 2008;9:532-544.
[PubMed]
21.
Hernandes MS, D'Avila JC, Trevelin SC, Reis PA, Kinjo ER, Lopes LR, Castro-Faria-Neto HC, Cunha FQ, Britto LR, Bozza FA: The role of Nox2-derived ROS in the development of cognitive impairment after sepsis. J Neuroinflammation 2014;11:36.
[PubMed]
22.
Hevner RF: Brain overgrowth in disorders of RTK-PI3K-AKT signaling: a mosaic of malformations. Semin Perinatol 2015;39:36-43.
[PubMed]
23.
Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK: Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013;155:1451-1463.
[PubMed]
24.
Kang DW, Park JG, Ilhan ZE, Wallstrom G, Labaer J, Adams JB, Krajmalnik-Brown R: Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS One 2013;8:e68322.
[PubMed]
25.
Kohane IS, McMurry A, Weber G, MacFadden D, Rappaport L, Kunkel L, Bickel J, Wattanasin N, Spence S, Murphy S, Churchill S: The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS One 2012;7:e33224.
[PubMed]
26.
Kotagal S, Broomall E: Sleep in children with autism spectrum disorder. Pediatr Neurol 2012;47:242-251.
[PubMed]
27.
Libbey JE, Fujinami RS: Role for antibodies in altering behavior and movement. Autism Res 2010;3:147-152.
[PubMed]
28.
Liu Z, Li N, Neu J: Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr 2005;94:386-393.
[PubMed]
29.
Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P, Roca J, Dore J: Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut 2006;55:205-211.
[PubMed]
30.
Martin FP, Wang Y, Sprenger N, Yap IK, Lundstedt T, Lek P, Rezzi S, Ramadan Z, van Bladeren P, Fay LB, Kochhar S, Lindon JC, Holmes E, Nicholson JK: Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model. Mol Syst Biol 2008;4:157.
[PubMed]
31.
Mazmanian SK, Round JL, Kasper DL: A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 2008;453:620-625.
[PubMed]
32.
Meyer U, Feldon J: Prenatal exposure to infection: a primary mechanism for abnormal dopaminergic development in schizophrenia. Psychopharmacology (Berl) 2009;206:587-602.
[PubMed]
33.
Meyer U, Nyffeler M, Yee BK, Knuesel I, Feldon J: Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice. Brain Behav Immun 2008;22:469-486.
[PubMed]
34.
Noriega DB, Savelkoul HF: Immune dysregulation in autism spectrum disorder. Eur J Pediatr 2014;173:33-43.
[PubMed]
35.
Onore C, Van de Water J, Ashwood P: Decreased levels of EGF in plasma of children with autism spectrum disorder. Autism Res Treat 2012;2012:205362.
[PubMed]
36.
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;54:987-991.
[PubMed]
37.
Pastorelli L, De Salvo C, Mercado JR, Vecchi M, Pizarro TT: Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics. Front Immunol 2013;4:280.
[PubMed]
38.
Peeters TL: Gastrointestinal hormones and gut motility. Curr Opin Endocrinol Diabetes Obes 2015;22:9-13.
[PubMed]
39.
Petrof EO, Khoruts A: From stool transplants to next-generation microbiota therapeutics. Gastroenterology 2014;146:1573-1582.
[PubMed]
40.
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Jian M, Zhou Y, Li Y, Zhang X, Qin N, Yang H, Wang J, Brunak S, et al: A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010;464:59-65.
[PubMed]
41.
Ramalingam M, Kim SJ: Reactive oxygen/nitrogen species and their functional correlations in neurodegenerative diseases. J Neural Transm 2012;119:891-910.
[PubMed]
42.
Round JL, Mazmanian SK: Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA 2010;107:12204-12209.
[PubMed]
43.
Schippa S, Conte MP: Dysbiotic events in gut microbiota: impact on human health. Nutrients 2014;6:5786-5805.
[PubMed]
44.
Selhub EM, Logan AC, Bested AC: Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. J Physiol Anthropol 2014;33:2.
[PubMed]
45.
Smith SE, Li J, Garbett K, Mirnics K, Patterson PH: Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci 2007;27:10695-10702.
[PubMed]
46.
Sorce S, Krause KH: Nox enzymes in the central nervous system: from signaling to disease. Antioxid Redox Signal 2009;11:2481-2504.
[PubMed]
47.
Swaminath A: The power of poop: patients getting ahead of their doctors using self-administered fecal transplants. Am J Gastroenterol 2014;109:777-778.
[PubMed]
48.
Sweeten TL, Bowyer SL, Posey DJ, Halberstadt GM, McDougle CJ: Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders. Pediatrics 2003;112:e420.
[PubMed]
49.
Tang F, Reddy BL, Saier MH Jr: Psychobiotics and their involvement in mental health. J Mol Microbiol Biotechnol 2014;24:211-214.
[PubMed]
50.
Tapryal N, Mukhopadhyay C, Das D, Fox PL, Mukhopadhyay CK: Reactive oxygen species regulate ceruloplasmin by a novel mRNA decay mechanism involving its 3′-untranslated region: implications in neurodegenerative diseases. J Biol Chem 2009;284:1873-1883.
[PubMed]
51.
Turner JR: Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009;9:799-809.
[PubMed]
52.
Volk HE, Kerin T, Lurmann F, Hertz-Picciotto I, McConnell R, Campbell DB: Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene. Epidemiology 2014;25:44-47.
[PubMed]
53.
Whitehouse AJ, Stanley FJ: Is autism one or multiple disorders? Med J Aust 2013;198:302-303.
[PubMed]
54.
Williams BL, Hornig M, Buie T, Bauman ML, Cho Paik M, Wick I, Bennett A, Jabado O, Hirschberg DL, Lipkin WI: Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One 2011;6:e24585.
[PubMed]
55.
Williams BL, Hornig M, Parekh T, Lipkin WI: Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. MBio 2012;3:e00261-11.
[PubMed]
56.
Williams BT, Gray KM: The relationship between emotion recognition ability and social skills in young children with autism. Autism 2013;17:762-768.
[PubMed]
57.
Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral DG, Van de Water J: Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders. Brain Behav Immun 2009;23:64-74.
[PubMed]
58.
Yong E: Faecal transplants succeed in clinical trial. Unorthodox technique is far more effective than antibiotics at treating recurrent gut infections. Nature 2013, DOI: 10.1038/nature.2013.12227.
59.
Zerbo O, Qian Y, Yoshida C, Grether JK, Van de Water J, Croen LA: Maternal infection during pregnancy and autism spectrum disorders. J Autism Dev Disord 2013, Epub ahead of print.
[PubMed]
60.
Zhang QB, Gao SJ, Zhao HX: Thioredoxin: a novel, independent diagnosis marker in children with autism. Int J Dev Neurosci 2015;92-96.
[PubMed]
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