Honor thy symbionts

Abstract

Our intestine is the site of an extraordinarily complex and dynamic environmentally transmitted consortial symbiosis. The molecular foundations of beneficial symbiotic host-bacterial relationships in the gut are being revealed in part from studies of simplified models of this ecosystem, where germ-free mice are colonized with specified members of the microbial community, and in part from comparisons of the genomes of members of the intestinal microbiota. The results emphasize the contributions of symbionts to postnatal gut development and host physiology, as well as the remarkable strategies these microorganisms have evolved to sustain their alliances. These points are illustrated by the human-Bacteroides thetaiotaomicron symbiosis. Interdisciplinary studies of the effects of the intestinal environment on genome structure and function should provide important new insights about how microbes and humans have coevolved mutually beneficial relationships and new perspectives about the foundations of our health.

Fig. 1.

Strategies used by B. thetaiotaomicron and Bifidobacterium longum to regulate expression of their glycobiomes. B. thetaiotaomicron has an elaborate apparatus for retrieving polysaccharides from the luminal environment (SusC/D outer membrane proteins) and hydrolyzing them to oligosaccharides (secreted extracellular and periplasmic glycosylhydrolases). A highly developed environmental sensing apparatus, composed of ECF-type σ factors and hybrid two-component systems, is postulated to play a key role in regulating expression of components of its glycobiome and providing the means to behave as an adaptive forager of polysaccharides. ECF-typeσ factors are components of 12 gene clusters that contain downstream SusC/D homologs and glycosylhydrolases (one cluster is presented for illustration with the arrow indicating the direction of transcription). The Gram-positive bacterium, Bifidobacterium longum, has no SusC/D homologs but contains transporters that allow it to recover oligosaccharides generated from dietary polysaccharides by species such as B. thetaiotaomicron. An example is shown of one of the organism's seven gene clusters, each encoding MalEFG subunits of an oligosaccharide transporter, and glycosylhydrolases under the control of a LacI-type transcriptional repressor (51).

Fig. 2.

Phylogeny of Bacteroides and related species. Members of the Bacteroidales order are common inhabitants of the mammalian digestive tract. The order includes four established families: Bacteroidaceae, Porphyromonadaceae, Prevotellaceae, and Rikenellaceae. Porphyromonas gingivalis (Porphyromonadaceae family) is associated with periodontal disease of humans. Its genome has been sequenced (www.tigr.org/tdb/mdb/mdbinprogress.html). Bacteroides forsythus, now renamed Tannerella forsythensis (Porphyromonadaceae family), is a human dental pathogen that has been partially sequenced (198 contigs, ≈3.6 Mb, unpublished work; www.tigr.org/tdb/mdb/mdbinprogress.html). Prevotella ruminicola (Prevotellaceae family) is a prominent member of the rumen and plays a central role in ruminal digestion of feed proteins. Brackets denote that for these species, initial assignment to this genus was based on biochemical phenotype: their 16S rDNA sequences indicate that their membership in Bacteroides should be viewed as tentative (adapted from ref. 82).