Vitamin B12 as a modulator of gut microbial ecology

Abstract

The microbial mechanisms and key metabolites that shape the composition of the human gut microbiota are largely unknown, impeding efforts to manipulate dysbiotic microbial communities toward stability and health. Vitamins, which by definition are not synthesized in sufficient quantities by the host and can mediate fundamental biological processes in microbes, represent an attractive target for reshaping microbial communities. Here, we discuss how vitamin B12 (cobalamin) impacts diverse host-microbe symbioses. Although cobalamin is synthesized by some human gut microbes, it is a precious resource in the gut and is likely not provisioned to the host in significant quantities. However, this vitamin may make an unrecognized contribution in shaping the structure and function of human gut microbial communities.

Figure 1. Representative examples of corrinoid structural diversity

(Allen and Stabler, 2008; Renz, 1999).

Figure 2. Microbial corrinoid metabolism in the gut

In coprophagic and ruminant animals, gut microbes provide a direct source of cobalamin (direct effect) (Girard et al., 2009). In insects, corrinoids are essential cofactors for obligate symbionts that provide key nutrients to the host (indirect effect) (McCutcheon et al., 2009). Competition and exchange of corrinoids likely shape gut microbial community composition and expressed functions in humans and other animals (microbiome remodeling) (Allen and Stabler, 2008; Goodman et al., 2011; Seth and Taga, 2014).

Figure 3. Corrinoid composition of microbial communities measured by LCMS

A. The average corrinoid composition of fecal samples from 18 humans in the absence of cobalamin supplementation (Human); a groundwater enrichment community amended with trichloroethene (GW); and bovine rumen (Rumen) is shown (adapted with permission from (Allen and Stabler, 2008; Girard et al., 2009; Men et al., 2014b)). B. Corrinoid composition of fecal samples from 20 individuals (adapted with permission from (Allen and Stabler, 2008)). Asterisks indicate individuals supplemented daily with ≤25 μg cobalamin. Double asterisks indicate individuals supplemented daily with ≤1,000 μg cobalamin. Corrinoid abbreviations are defined in Box 1.