1. (A) Metabolic niches in the gut microbiome.
(A) Metabolic niches in the gut microbiome. The localization and spatial organization of the gut microbiota are not uniform along the gastrointestinal tract. This dynamic gut ecosystem consists of many unique features, such as microniches, pH gradients, and dynamic microbe–tissue interactions of relevance for microbial biotransformations. The highest density of bacteria is present in the large intestine, with recent estimates of 1013 bacterial cells in the large intestine associated with microbial genes encoding a broad range of enzymes necessary for xenobiotic biotransformation. These bacteria are likely most important for pharmacomicrobiomics and reside in a reaction chamber with a mean pH of 6.4–7 and a lower redox potential than other gastrointestinal niches. Oxygen partial pressures along the gastrointestinal tract also contribute to these metabolic niches. (B) Factors affecting the composition and function of the large intestine metabolic niche. The compositional characteristics of the gut microbiome are influenced by a number of factors, with the initial seeding and trajectory toward an healthy adult-like diversity and stability determined by mode of delivery (C-section vs. par vaginum) and early feeding patterns (breast feeding vs. formula feeding). Host genetics also plays a role as does geographical location, whereas stress across the life span may be viewed as a threat to the diversity of the gut microbiome. A Westernized diet is also thought to compromise the integrity of the gut microbiome, whereas increased fiber intake is associated with increased diversity. Exercise might also promote the stability of a health microbiome, although the ageing process is associated with a narrowing diversity, as are many disease states and excessive/inappropriate antibiotic use. A number of intrinsic factors, reviewed in details elsewhere by Simren et al. (2013) and partially depicted here, also determine the composition of the gut microbiome, including gastric acid secretion, anticommensal sIgA and antimicrobial peptide production, and gastrointestinal motility.
Gerard Clarke et al. Pharmacol Rev 2019;71:
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