Commensal Resilience Mechanisms in the Inflamed Intestine

The gut microbial community is constantly subjected to perturbations such as intestinal inflammation, which could drive the microbiota into a perturbed state termed dysbiosis. Research in the microbiome has primarily focused on the factors that induce changes in the gut microbial community, while little is known about how the microbiota responds to perturbations and remains resilient. A hallmark change that occurs during episodes of intestinal inflammation is the marked reduction of iron bioavailability, a consequence of a series of host processes known as nutritional immunity. Pathogenic bacterial such as Salmonella Typhimurium (S. Tm) have evolved to produce small, high-affinity iron-chelating molecules termed siderophores to overcome host nutritional immunity and thrive in the inflamed intestine. Here, we show that commensal gut Bacteroides thetaiotaomicron (B. theta) acquires iron in the inflamed gut by pirating siderophores from an enteric pathogen that causes intestinal iron limitation. Notably, B. theta captures siderophores using a unique system absent in other Gram-negative bacteria. However, such a capture mechanism can be exploited by enteric pathogens to “re-pirate” siderophores from gut commensals to evade nutritional immunity, adding a previously unappreciated dimension to the intricate interactions between pathogen and nutritional immunity.