Major Histocompatibility Complex class IIb polymorphism influences gut microbiota composition and diversity

Abstract

Animals harbour diverse communities of symbiotic bacteria, which differ dramatically among host individuals. This heterogeneity poses an immunological challenge: 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 show that MHC IIb polymorphism is associated with among-individual variation in gut microbiota within a single wild vertebrate population of a small fish, the threespine stickleback. We sampled stickleback from Cedar Lake, on Vancouver Island, and used next-generation sequencing to genotype the sticklebacks' gut microbiota (16S sequencing) and their MHC class IIb exon 2 sequences. The presence of certain MHC motifs was associated with altered relative abundance (increase or decrease) of some microbial Families. The effect sizes are modest and entail a minority of microbial taxa, but these results represent the first indication that MHC genotype may affect gut microbiota composition in natural populations (MHC-microbe associations have also been found in a few studies of lab mice). Surprisingly, these MHC effects were frequently sex-dependent. Finally, hosts with more diverse MHC motifs had less diverse gut microbiota. One implication is that MHC might influence the efficacy of therapeutic strategies to treat dysbiosis-associated disease, including the outcome of microbial transplants between healthy and diseased patients. We also speculate that macroparasite-driven selection on MHC has the potential to indirectly alter the host gut microbiota, and vice versa.

Dietary input of microbes and host genetic variation shape among-population differences in stickleback gut microbiota

“…The physiological mechanisms underlying these effects are not known at present. However, the results presented here are consistent with a recent study from a single population of stickleback, showing that individuals with more diverse Major Histocompatibility Complex class II (MHC II) alleles have less diverse gut microbiota (Bolnick et al, 2014a). We speculate that the effect of overall heterozygosity described here may be a proxy for immunogenetic diversity (possibly at the MHC), which tends to reduce microbial diversity.…”

“…After accounting for habitat and population effects, there remained substantial residual variation in microbial community composition, which likely reflects among-host variation in diet 2014b, c) and genotype (Bolnick et al, 2014a). Little Mud Lake Blackwater Lake Population Figure 5 Alpha diversity levels (# OTUs) of stickleback gut microbiotas after rarefaction to 3000.…”

“…Stickleback populations also exhibit varying levels of genetic divergence, arising from both neutral evolution and divergent natural selection. This genetic divergence is especially striking for some immune genes, including but not limited to MHC class II (Stutz and Bolnick, 2014), which can regulate microbial persistence within the host gut (Bolnick et al, 2014a). Consequently, environmental and host genetic divergence among stickleback populations provides an opportunity to partition the effects of colonization and host genetic filtering on gut microbial metapopulation structure in a wild animal species.…”

“…We infer that colonization effects, at least as measured by water and prey microbes, are weak compared with genotype effects in microbial species sorting. Such genetic control could arise either through genetic differences in mucosal immune function (for example, MHC genotype, Bolnick et al, 2014a) or through genetically based differences in host ecology (for example, diet; Bolnick et al, 2014c). Surprisingly, populations with greater genetic heterozygosity tended to exhibit lower amongindividual microbial variation.…”

Divergence across diet, time and populations rules out parallel evolution in the gut microbiomes of Trinidadian guppies

“…complex alleles are related to the composition and diversity of gut bacteria in freshwater stickleback fish (Bolnick et al, 2014a). Differences in these or other genetic attributes among guppy individuals and populations could be key to understanding the causes of their microbiome divergence.…”