In sickness and health: Effects of gut microbial metabolites on human physiology

Abstract

The connection between intestinal microbes and human health has been appreciated since the 1880s with Theodor Escherich's investigation of Escherichia coli and other fecal bacteria. Escherich hypothesized that indigenous micoorganisms play roles in both digestion and intestinal diseases In the last century, our understanding of the bacteria, viruses, archaea, and eukaryotes that normally inhabit the gut has expanded alongside the rest of the field of microbiology, and numerous fundamental roles have been established for this community, now termed the microbiome. As speculated by Escherich, these roles definitively include nutrient digestion [2, 3] and protection from invading pathogens [4] but also extend to short-and long-term instruction of the immune system [5-7] and production of a wide range of metabolites that are unable to be produced by human physiology. Although the gut microbiome is typically described as being composed of nonharmful or beneficial microorganisms, it is now appreciated that both individual species [8] or multiple community members acting together [9, 10] can exert pathogenic effects, which are often more subtle than those of classical pathogens. Indeed, the presence of common intestinal microorganisms with discrete virulence factors (e.g., enterotoxins, genotoxins) that may only manifest in diseases like colorectal cancer or inflammatory bowel disease (IBD) over long periods of time or in certain host genetic backgrounds obscures the definition of pathogen.

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