Skip to main content

Advertisement

Log in

The Gut Microbiome: A New Frontier in Autism Research

  • Genetic Disorders (JF Cubells and EB Binder, Section Editors)
  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

The human gut harbors a complex community of microbes that profoundly influence many aspects of growth and development, including development of the nervous system. Advances in high-throughput DNA sequencing methods have led to rapidly expanding knowledge about this gut microbiome. Here, we review fundamental emerging data on the human gut microbiome, with a focus on potential interactions between the microbiome and autism spectrum disorders (ASD) and consider research on atypical patterns of feeding and nutrition in ASD and how they might interact with the microbiome. Finally we selectively survey results from studies in rodents on the impact of the microbiome on neurobehavioral development. The evidence reviewed here suggests that a deeper understanding of the gut microbiome could open up new avenues of research on ASD, including potential novel treatment strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Whitman WB, Coleman DC, Wiebe WJ. Prokaryotes: the unseen majority. Proc Natl Acad Sci U S A. 1998;95:6578–83.

    Article  PubMed  CAS  Google Scholar 

  2. Gill SR, et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355–9.

    Article  PubMed  CAS  Google Scholar 

  3. Zhu B, Wang X, Li L. Human gut microbiome: the second genome of human body. Protein Cell. 2010;1:718–25.

    Article  PubMed  Google Scholar 

  4. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148:1258–70.

    Article  PubMed  CAS  Google Scholar 

  5. Peterson J, et al. The NIH human microbiome project. Genome Res. 2009;19:2317–23.

    Article  PubMed  Google Scholar 

  6. O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006;7:688–93.

    Article  PubMed  Google Scholar 

  7. •• A framework for human microbiome research. Nature 2012;486:215-21. One of the initial publications from the Human Microbiome Project, showing the diversity of data contained in the microbiome from different body sites.

  8. Cummings JH, Macfarlane GT. Role of intestinal bacteria in nutrient metabolism. JPEN J Parenter Enter. 1997;21:357–65.

    Article  CAS  Google Scholar 

  9. Staley JT, Konopka A. Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats. Ann Rev Microbiol. 1985;39:321–46.

    Article  CAS  Google Scholar 

  10. Wade W. Unculturable bacteria–the uncharacterized organisms that cause oral infections. J R Soc Med. 2002;95:81–3.

    Article  PubMed  Google Scholar 

  11. Duncan SH, Louis P, Flint HJ. Cultivable bacterial diversity from the human colon. Lett Appl Microbiol. 2007;44:343–50.

    Article  PubMed  CAS  Google Scholar 

  12. Eckburg PB, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–8.

    Article  PubMed  Google Scholar 

  13. Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008;26:1135–45.

    Article  PubMed  CAS  Google Scholar 

  14. Pace NR. A molecular view of microbial diversity and the biosphere. Science. 1997;276:734–40.

    Article  PubMed  CAS  Google Scholar 

  15. Venter JC, et al. Environmental genome shotgun sequencing of the Sargasso Sea. Science. 2004;304:66–74.

    Article  PubMed  CAS  Google Scholar 

  16. Momozawa Y, Deffontaine V, Louis E, Medrano JF. Characterization of bacteria in biopsies of colon and stools by high throughput sequencing of the V2 region of bacterial 16S rRNA gene in human. PLoS One. 2011;6:e16952.

    Article  PubMed  CAS  Google Scholar 

  17. •• Arumugam M, et al. Enterotypes of the human gut microbiome. Nature. 2011;473:174–80. The first paper with data to support the idea of characteristic gut microbiomes, classified as "enterotypes..

    Article  PubMed  CAS  Google Scholar 

  18. Wu GD, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334:105–8.

    Article  PubMed  CAS  Google Scholar 

  19. • Koenig JE, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4578–85. This study measured the developing infant gut microbiome by sampling stool from a single healthy infant 60 times, from birth to 2.5 years of age..

    Article  PubMed  CAS  Google Scholar 

  20. Breitbart M, et al. Viral diversity and dynamics in an infant gut. Res Microbiol. 2008;159:367–73.

    Article  PubMed  CAS  Google Scholar 

  21. Dominguez-Bello MG, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107:11971–5.

    Article  PubMed  Google Scholar 

  22. • Schwartz S, et al. A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response. Genome Biol. 2012;13:r32. This study compared both the developing gut microbiome and gene expression in 6 breastfed infants and 6 formula fed infants, finding systematic differences in the microbiome and in expression of genes relevant to immune system fucntion..

    Article  PubMed  CAS  Google Scholar 

  23. Qin J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.

    Article  PubMed  CAS  Google Scholar 

  24. Bergman EN. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol Rev. 1990;70:567–90.

    PubMed  CAS  Google Scholar 

  25. Walter J, Ley R. The human gut microbiome: ecology and recent evolutionary changes. Annu Rev Microbiol. 2011;65:411–29.

    Article  PubMed  CAS  Google Scholar 

  26. Chow J, Lee SM, Shen Y, Khosravi A, Mazmanian SK. Host-bacterial symbiosis in health and disease. Adv Immunol. 2010;107:243–74.

    Article  PubMed  CAS  Google Scholar 

  27. Kaplan JL, Shi HN, Walker WA. The role of microbes in developmental immunologic programming. Pediatr Res. 2011;69:465–72.

    Article  PubMed  Google Scholar 

  28. Gaboriau-Routhiau V, et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009;31:677–89.

    Article  PubMed  CAS  Google Scholar 

  29. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122:107–18.

    Article  PubMed  CAS  Google Scholar 

  30. Turnbaugh PJ, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–4.

    Article  PubMed  CAS  Google Scholar 

  31. Wang Z, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57–63.

    Article  PubMed  CAS  Google Scholar 

  32. Finegold SM, et al. Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe. 2011;16:444–53.

    Article  Google Scholar 

  33. 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;54:987–91.

    Article  PubMed  Google Scholar 

  34. Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol. 2004;70:6459–65.

    Article  PubMed  CAS  Google Scholar 

  35. Curran LK, et al. Behaviors associated with fever in children with autism spectrum disorders. Pediatrics. 2007;120:e1386–92.

    Article  PubMed  Google Scholar 

  36. Sandler RH, et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000;15:429–35.

    Article  PubMed  CAS  Google Scholar 

  37. Critchfield JW, van Hemert S, Ash M, Mulder L, Ashwood P. The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterol Res Pract. 2011;2011:161358.

    PubMed  Google Scholar 

  38. Gueimonde M, Laitinen K, Salminen S, Isolauri E. Breast milk: a source of bifidobacteria for infant gut development and maturation? Neonatology. 2007;92:64–6.

    Article  PubMed  Google Scholar 

  39. Le Huerou-Luron I, Blat S, Boudry G. Breast- v. formula-feeding: impacts on the digestive tract and immediate and long-term health effects. Nutr Res Rev. 2010;23:23–36.

    Article  PubMed  Google Scholar 

  40. Martin R, Heilig GH, Zoetendal EG, Smidt H, Rodriguez JM. Diversity of the Lactobacillus group in breast milk and vagina of healthy women and potential role in the colonization of the infant gut. J Appl Microbiol. 2007;103:2638–44.

    Article  PubMed  CAS  Google Scholar 

  41. Sinkiewicz G, Nordsröm EA. Occurrence of lactobacillus reuteri, lactobacilli, and bifidobacteria in human breast milk. In: European Society For Pediatric Research (ESPR), Vol. 58 415, 2005. (Occurrence of lactobacillus reuteri, lactobacilli, and bifidobacteria in human breast milk, Sienna, Italy).

  42. Partty A, Kalliomaki M, Endo A, Salminen S, Isolauri E. Compositional development of Bifidobacterium and Lactobacillus microbiota is linked with crying and fussing in early infancy. PLoS One. 2012;7:e32495.

    Article  PubMed  CAS  Google Scholar 

  43. Menard O, Butel MJ, Gaboriau-Routhiau V, Waligora-Dupriet AJ. Gnotobiotic mouse immune response induced by Bifidobacterium sp. strains isolated from infants. Appl Environ Microb. 2008;74:660–6.

    Article  CAS  Google Scholar 

  44. Ouwehand AC, et al. Differences in Bifidobacterium flora composition in allergic and healthy infants. J Allergy Clin Immunol. 2001;108:144–5.

    Article  PubMed  CAS  Google Scholar 

  45. Kalliomaki M, et al. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol. 2001;107:129–34.

    Article  PubMed  CAS  Google Scholar 

  46. Bier JA, Oliver T, Ferguson AE, Vohr BR. Human milk improves cognitive and motor development of premature infants during infancy. J Hum Lact: Off J Int Lact Consult Assoc. 2002;18:361–7.

    Article  Google Scholar 

  47. Spor A, Koren O, Ley R. Unravelling the effects of the environment and host genotype on the gut microbiome. Nat Rev Microbiol. 2011;9:279–90.

    Article  PubMed  CAS  Google Scholar 

  48. Turnbaugh PJ, Backhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3:213–23.

    Article  PubMed  CAS  Google Scholar 

  49. Vijay-Kumar M, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328:228–31.

    Article  PubMed  CAS  Google Scholar 

  50. Rhoads JM, et al. Altered fecal microflora and increased fecal calprotectin in infants with colic. J Pediatr. 2009;155:823–8. e821.

    Article  PubMed  CAS  Google Scholar 

  51. Savino F, et al. Bacterial counts of intestinal Lactobacillus species in infants with colic. Pediatr Allergy Immunol: Off Publ Eur Soc Pediatr Allergy Immunol. 2005;16:72–5.

    Article  CAS  Google Scholar 

  52. Horwood LJ, Fergusson DM. Breastfeeding and later cognitive and academic outcomes. Pediatrics. 1998;101:E9.

    Article  PubMed  CAS  Google Scholar 

  53. Al-Farsi YM, et al. Effect of suboptimal breast-feeding on occurrence of autism: a case-control study. Nutrition. 2012;28:e27–32.

    Article  PubMed  Google Scholar 

  54. Tanoue Y, Oda S. Weaning time of children with infantile autism. J Autism Dev Disord. 1989;19:425–34.

    Article  PubMed  CAS  Google Scholar 

  55. Schultz ST, et al. Breastfeeding, infant formula supplementation, and autistic disorder: the results of a parent survey. Int Breastfeed J. 2006;1:16.

    Article  PubMed  Google Scholar 

  56. Ledford JR, Gast DL. Feeding problems in children with autism spectrum disorders: a review. Focus Autism Other Dev Disabl. 2006;21:153–66.

    Article  Google Scholar 

  57. Field D, Garland M, Williams K. Correlates of specific childhood feeding problems. J Paediatr Child Health. 2003;39:299–304.

    Article  PubMed  CAS  Google Scholar 

  58. Sharp WG, Jaquess DL, Luckens CT. Multi-method assessment of feeding problems among children with autism spectrum disorders. Res Autism Spectr Disord. 2012;7:56–65.

    Article  Google Scholar 

  59. Hediger ML, et al. Reduced bone cortical thickness in boys with autism or autism spectrum disorder. J Autism Dev Disord. 2008;38:848–56.

    Article  PubMed  Google Scholar 

  60. Bandini LG, et al. Food selectivity in children with autism spectrum disorders and typically developing children. J Pediatr. 2010;157:259–64.

    Article  PubMed  Google Scholar 

  61. Zimmer MH, et al. Food variety as a predictor of nutritional status among children with autism. J Autism Dev Disord. 2012;42:549–56.

    Article  PubMed  Google Scholar 

  62. Huncharek M, Kupelnick B. Dietary fat intake and risk of epithelial ovarian cancer: a meta-analysis of 6,689 subjects from 8 observational studies. Nutr Cancer. 2011;40:87–91.

    Article  Google Scholar 

  63. Mente A, de Koning L, Shannon HS, Anand SS. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med. 2009;169:659–69.

    Article  PubMed  CAS  Google Scholar 

  64. Sharp WG, Jaquess DL, Morton JF, Herzinger CV. Pediatric feeding disorders: a quantitative synthesis of treatment outcomes. Clin Child Fam Psychol Rev. 2010;13:348–65.

    Article  PubMed  Google Scholar 

  65. Buie T, et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010;125 Suppl 1:S1–18.

    Article  PubMed  Google Scholar 

  66. Ibrahim SH, Voigt RG, Katusic SK, Weaver AL, Barbaresi WJ. Incidence of gastrointestinal symptoms in children with autism: a population-based study. Pediatrics. 2009;124:680–6.

    Article  PubMed  Google Scholar 

  67. Matson JL, Fodstad JC. The treatment of food selectivity and other feeding problems in children with autism spectrum disorders. Res Autism Spect Dis. 2009;3:455–61.

    Article  Google Scholar 

  68. Ahearn WH, Castine T, Nault K, Green G. An assessment of food acceptance in children with autism or pervasive developmental disorder-not otherwise specified. J Autism Dev Disord. 2001;31:505–11.

    Article  PubMed  CAS  Google Scholar 

  69. Williams BL, et al. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One. 2011;6:e24585.

    Article  PubMed  CAS  Google Scholar 

  70. Piazza CC, et al. Functional analysis of inappropriate mealtime behaviors. J Appl Behav Anal. 2003;36:187–204.

    Article  PubMed  Google Scholar 

  71. Nikolov RN, et al. Gastrointestinal symptoms in a sample of children with pervasive developmental disorders. J Autism Dev Disord. 2009;39:405–13.

    Article  PubMed  Google Scholar 

  72. Whorwell PJ, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101:1581–90.

    Article  PubMed  Google Scholar 

  73. •• Rhee SH, Pothoulakis C, Mayer EA. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol. 2009;6:306–14. An excellent overview of the cellular and biochemical pathways of interaction among the gut, brain, and microbiome..

    Article  PubMed  CAS  Google Scholar 

  74. Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci. 2011;12:453–66.

    Article  PubMed  CAS  Google Scholar 

  75. Sudo N. Role of microbiome in regulating the HPA axis and its relevance to allergy. Chem Immunol Allergy. 2012;98:163–75.

    Article  PubMed  CAS  Google Scholar 

  76. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9:313–23.

    Article  PubMed  CAS  Google Scholar 

  77. Diaz Heijtz R, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A. 2011;108:3047–52.

    Article  PubMed  Google Scholar 

  78. Clarke G, et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatr. 2012. doi:10.1038/mp.2012.77.

  79. Bercik P, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011;141:599–609. 609 e591-593.

    Article  PubMed  CAS  Google Scholar 

  80. Tang X, Orchard SM, Sanford LD. Home cage activity and behavioral performance in inbred and hybrid mice. Behav Brain Res. 2002;136:555–69.

    Article  PubMed  Google Scholar 

Download references

Disclosure

J. G. Mulle: research support from the National Institutes of Health (NIH) and consultant to the Centers for Disease Control and Prevention; W. G. Sharp: research support from the Children’s Healthcare of Atlanta Trust Pilot Award; J. F. Cubells: research support from NIH, Roche, Seaside Therapeutics, and Biomarin and consultant to Abbott Laboratories, Novartis, Barnes and Thornberg, LLP, and the University of Nebraska.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jennifer G. Mulle.

Additional information

This article is part of the Topical Collection on Genetic Disorders

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mulle, J.G., Sharp, W.G. & Cubells, J.F. The Gut Microbiome: A New Frontier in Autism Research. Curr Psychiatry Rep 15, 337 (2013). https://doi.org/10.1007/s11920-012-0337-0

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11920-012-0337-0

Keywords

Navigation