Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla

Abstract

The adult human gut houses a bacterial community containing trillions of members comprising thousands of species-level phylogenetic types (phylotypes). Culture-independent surveys of this community have revealed remarkable interpersonal variations in these strain- and species-level phylotypes. Two bacterial phyla, the Firmicutes and the Bacteroidetes, commonly dominate this ecosystem (1), as they do in the guts of at least 60 mammalian species (2).

Comparative analysis of 5 previously sequenced human gut Bacteroidetes revealed that each genome contains a large repertoire of genes involved in acquisition and metabolism of polysaccharides. This repertoire includes (i) up to hundreds of glycoside hydrolases (GHs) and polysaccharide lyases (PLs); (ii) myriad paralogs of SusC and SusD, outer membrane proteins involved in recognition and import of specific carbohydrate structures (3); and (iii) a large array of environmental sensors and regulators (4). These genes are assembled in similarly organized, selectively regulated polysaccharide utilization loci (PULs) that encode functions necessary to detect, bind, degrade and import carbohydrate species encountered in the gut habitat–either from the diet or from host glycans associated with mucus and the surfaces of epithelial cells (5–7). Studies of gnotobiotic mice colonized only with human gut-derived Bacteroides thetaiotaomicron have demonstrated that this organism can vary its pattern of expression of PULs as a function of diet, e.g., during the transition from mother’s milk to a polysaccharide-rich chow consumed when mice are weaned (5), or when adult mice are switched from a diet rich in plant polysaccharides to a diet devoid
these glycans and replete with simple sugars (under the latter conditions, the organism forages on host glycans) (6, 7).

Our previous functional genomic studies of the responses of B. hetaiotaomicron to cocolonization of the guts of gnotobiotic with Bifidobacterium longum, an Actinobacterium found in the intestines of adults and infants, or with Lactobacillus casei, a Firmicute present in a number of fermented diary products, have shown that B. thetaiotaomicron adapts to the presence of these other microbes by modifying expression of its PULs in ways that expand the breadth of its carbohydrate foraging activities (8). These observations support the notion that gut microbes may live at the intersection of 2 forms of selective pressure: bottom-up selection, where fierce competition between members of a community that approaches a population density of 1011 to 1012 organisms per milliliter of colonic contents drives phylotypes to assume distinct functional roles (niches); and top-down selection, where the host selects for functional redundancy to ensure against the failure of bioreactor functions that could prove highly deleterious (9, 10).