Immunity: Regulation by the Indigenous Gastrointestinal Microbiota

Abstract

Human beings are colonised by a beneficial ecosystem of microorganisms collectively termed the commensal microbiota or microbiome. Predominantly found at mucosal surfaces, these organisms are most abundant in the lower gastrointestinal tract. While the majority cannot be cultured outside the body, the development of molecular biological techniques (e.g. 16S ribosomal RNA PCR and shotgun metagenomic sequencing) is now allowing investigators to explore the microbiota in unprecedented detail. Research has uncovered a complex interplay between the intestinal microbiome and the host immune system. Gnotobiotic and germ‐free animal systems have revealed an absolute requirement for commensal microbes during normal immune development, and these interactions continue to shape immunity throughout adult life. In man, alterations to the normal intestinal microbiota (termed ‘dysbiosis’) have been associated with inflammatory bowel diseases, systemic autoimmune, metabolic and even neurological disorders.

Key Concepts

  • A human being is a ‘metaorganism’ – all mucosal surfaces are colonised by commensal microorganisms, collectively termed the microbiome.
  • Microbes are most abundant in the lower GI tract. The intestinal microbiota provides the host with vital nutrients and prevents colonisation by pathogens.
  • Novel molecular biology techniques (e.g. 16S rRNA PCR and shotgun metagenomic sequencing) are opening up the microbiome for in‐depth study.
  • The human microbiome project has identified >10 000 different species associated with humans with individuals carrying 200–400 species in the gut.
  • Colonization begins in the womb, continues during birth and normally reaches equilibrium by 2–3 years of age.
  • The microbiota regulates the intestinal immune system by stimulating the epithelial barrier, promoting release of secretory IgA by plasma B cells and inducing the development of homeostatic Th17/Treg populations in the gut mucosa.
  • Intestinal microbes can also influence systemic immunity via the production of bioactive molecules, such as pattern recognition receptor agonists (e.g. LPS), short‐chain fatty acids, tryptophan and polyamines.
  • Abnormal changes in the microbiota are associated with chronic inflammatory diseases, allergic inflammation, metabolic and neurological diseases.

Keywords: microbiota; commensalism; mucosal immunity; pattern recognition receptors; intestinal epithelium; antimicrobial peptides; secretory IgA; regulatory T cells; Th17; dysbiosis

Figure 1. Common sampling sites and culture‐independent techniques used to investigate the human microbiome.
Figure 2. The intestinal microbiome influences epithelial barrier functions; goblet cell numbers and mucus release; production of antimicrobial peptides (AMPs) by Paneth cells; induction and secretion of sIgA by B cells; the balance of Treg/Th17 populations; intraepithelial cell (IEC) and innate lymphoid cell (ILC) differentiation and functions; macrophage migration and functions.
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Further Reading

Blaser MJ and Falkow S (2009) What are the consequences of the disappearing human microbiota? Nature Reviews Microbiology 7: 887–894.

Hand TW (2016) The role of the microbiota in shaping infectious immunity. Trends in Immunology 37: 647–657.

Hand TW, Vujkovic‐Cvilin I, Ridaura VK and Belkaid Y (2016) Linking the microbiota, chronic disease, and the immune system. Trends in Endocrinology & Metabolism 12: 831–843.

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Butler, Matt(Apr 2017) Immunity: Regulation by the Indigenous Gastrointestinal Microbiota. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000941.pub2]