The intestinal microbiota and chronic disorders of the gut

Abstract

Mucosal surfaces of the gut are colonized by large numbers of heterogeneous bacteria that contribute to intestinal health and disease. In genetically susceptible individuals, a 'pathogenic community' may arise, whereby abnormal gut flora contributes to alterations in the mucosa and local immune system leading to gastrointestinal disease. These diseases include enteric infections, such as Clostridium difficile infection, small intestinal bacterial overgrowth, functional gastrointestinal disorders (including IBS), IBD and colorectal cancer. Prebiotics, probiotics and synbiotics (a combination of prebiotics and probiotics) have the capacity to reverse pathologic changes in gut flora and local immunity. Intestinal health and disease need to be thoroughly characterized to understand the interplay between the indigenous microbiota, the immune system and genetic host factors. This Review provides a broad overview of the importance of the intestinal microbiota in chronic disorders of the gut.

Key Points

  • The intestinal microbiota consists of heterogeneous and largely nonculturable bacteria that orchestrate homeostasis by communicating with the epithelium and innate and adaptive immune mechanisms of the gut

  • Host immunity is directly involved in the control of the intestinal microbiota and susceptibility to chronic intestinal disease

  • Enteric infection by a high-grade bacterial pathogen can alter susceptibility to IBS by producing chronic intestinal inflammation and a series of events that leads to altered bowel function

  • Certain bacteria in the lumen of the gut can cross the intestinal mucosa, causing systemic infection in a process called 'translocation'

  • In IBD, abnormal gut flora (which may include pathogenic species) and the presence of bacterial antigens with biologic properties produce a 'pathogenic community', leading to intestinal inflammation

  • Modulation of the intestinal microbiota may be possible through diet or by administration of prebiotics, probiotics, synbiotics, or by fecal transplantation of donor stool from a healthy individual

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Figure 1: The homeostatic role of the intestinal microbiota.
Figure 2: Pathogenesis of IBS and postinfectious IBS.
Figure 3: The role of intestinal microbiota and enteric pathogens in the pathogenesis of IBD.

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Both authors contributed equally to all aspects of this manuscript.

Correspondence to Andrew W. DuPont.

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A. W. DuPont receives grant/research support from Salix Pharmaceuticals and is a consultant for Lexicon Pharmaceuticals. H. L. DuPont receives grant/research support from Intercell, Osel Inc., Santarus and Novartis. He acts as a consultant, is on the speakers bureau and receives grant/research support from Salix Pharmaceuticals.

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DuPont, A., DuPont, H. The intestinal microbiota and chronic disorders of the gut. Nat Rev Gastroenterol Hepatol 8, 523–531 (2011). https://doi.org/10.1038/nrgastro.2011.133

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