Human gut bacteria harbor acquired interbacterial defense systems

The human gastrointestinal tract harbors a dense and diverse microbial community, the makeup of which is intimately linked to health. Extrinsic factors such as diet and host immunity are insufficient to explain the constituents of this community, implicating direct interactions between co-resident microbes as an important driver of microbiome composition. The genomes of bacteria derived from the gut microbiome are replete with pathways that mediate contact-dependent interbacterial antagonism(1–3). Many members of the Gram-negative order Bacteroidales encode the type VI secretion system (T6SS), which facilitates the delivery of toxic effector proteins into adjacent cells(4,5). Here we report the occurrence of acquired interbacterial defense (AID) gene clusters in Bacteroidales residing within the human gut microbiome. These clusters encode arrays of immunity genes that protect against T6SS-mediated intra- and inter-species bacterial antagonism. Moreover, the clusters reside on mobile elements and we demonstrate that their transfer is sufficient to confer toxin resistance in vitro and in gnotobiotic mice. Finally, we identify and validate the protective capacity of a recombinase-associated AID subtype (rAID-1) present broadly in Bacteroidales genomes. These rAID-1 gene clusters have a structure suggestive of active gene acquisition and include predicted immunity factors of toxins deriving from diverse organisms. Our data suggest that neutralization of contact-dependent interbacterial antagonism via AID systems shapes human gut microbiome ecology.