Metabolic Functions of the Microbiota
After characterizing microbial community membership and dynamics, it is critical to understand the functional activities that ultimately affect host physiology. Gut microbiota is integral to host digestion and nutrition, and they can generate nutrients from substrates that are otherwise indigestible by the host. For instance, xyloglucans are commonly found in dietary vegetables such as lettuce and onions, and the capacity for microbial digestion of xyloglucans was recently mapped to a single locus in a certain species of Bacteroides. The ability to digest xyloglucans was shown to be a relatively rare trait in members of the phylum Bacteroidetes, and the importance of this capability to the human host was demonstrated by analysis of a public metagenome database showing that 92% of individuals contained at least one of these rare Bacteroides spp. capable of digesting xyloglucans. These findings illustrate how humans have cultivated mutually beneficial relationships with gut microbiota with implications for diet and nutrition.
Microbes liberate short-chain fatty acids (SCFA) from indigestible dietary fibers, and SCFA are an important energy source for intestinal mucosa and critical for modulating immune responses and tumorigenesis in the gut. The role of butyrate, an abundant bioactive SCFA in the gut, plays a complex role in colon cancer that seems to be concentration and context dependent as illustrated by two recent preclinical studies. Butyrate was reported to promote tumorigenesis in transgenic mice with combined tumor suppressor gene (APC) mutation and mismatch repair gene (MSH2) deficiency because tumor formation was decreased by antibiotic treatment or low-carbohydrate diet, both of which decrease butyrate levels, and increased by feeding butyrate to antibiotic-treated mice. Conversely, butyrate was reported to inhibit tumorigenesis because mice deficient in Grp109a, a receptor for butyrate, had increased tumorigenesis promoted by inflammatory stimuli or APC mutation and signaling through Grp109a inhibited tumorigenesis induced by these stimuli. Further investigations into the role of butyrate produced by microbiota in colitis and colorectal cancer are awaited. The studies discussed in this section demonstrate the need to assess the function of the microbiota in order to better understand its role in health and disease.