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Microbial genome sequencing projects are beginning to provide insights about the molecular foundations of human–bacterial symbioses. The intestine contains our largest collection of symbionts, where members of Bacteroides comprise ∼25% of the microbiota in adults. The recently defined proteome of a prominent human intestinal symbiont, Bacteroides thetaiotaomicron, contains an elaborate environmental-sensing apparatus. This apparatus includes an unprecedented number of extracytoplasmic function (ECF) σ-factors, and a large collection of novel hybrid two-component systems composed of membrane-spanning periplasmic proteins with histidine kinase, phosphoacceptor, response regulator receiver and DNA-binding domains. These sensors are linked to the organism's large repertoire of genes involved in acquiring and processing dietary polysaccharides (‘the glycobiome'). This arrangement illustrates …