Individuals harbor diverse communities of symbiotic bacteria, which differ dramatically among host individuals. This heterogeneity poses an immunological challenge of distinguishing between mutualistic and pathogenic members of diverse and host-specific microbial communities. We propose that Major Histocompatibility class II (MHC) genotypes contribute to recognition and regulation of gut microbes, and thus MHC polymorphism contributes to microbial variation among hosts. Here, we confirm that, within a single wild vertebrate population of threespine stickleback, different MHC II amino acid sequence motifs are associated with among-individual variation in gut microbiota. The presence of certain MHC motifs is associated with altered relative abundance (increase or decrease) of some microbial Families. Furthermore, hosts with more diverse MHC motifs had less diverse gut microbiota. Our results show that MHC affects host regulation of gut microbiota in natural populations, consistent with limited experimental evidence that MHC controls gut microbes in laboratory mice. One implication is that MHC might influence the efficacy of therapeutic strategies to treat dysbiosis-associated disease. For example, we hypothesize that microbial transplants to treat dysbiosis might be constrained by MHC match between donor and recipient. Another implication is that macroparasite-driven selection on MHC has the potential to indirectly alter the host gut microbiota, and vice versa. Our findings therefore open up a variety of avenues for further investigation into MHC-microbiota interactions.

Bolnick MolecEcol Dryad SubmissionA zip file containing 14 .csv or .txt data files including fish metadata (morphology, sex, diet), gut microbiota composition, and MHC genotype.