Howard Hughes Medical Institute and Section of Integrative Biology, University of Texas at Austin, Austin, TX, 78712, USA.
Mol Ecol. 2014 Oct;23(19):4831-45. doi: 10.1111/mec.12846. Epub 2014 Jul 31.
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.
动物体内栖息着多样的共生菌群，这些菌群在宿主个体之间存在显著差异。这种异质性构成了免疫挑战：区分多样化且具有宿主特异性的微生物群落中的互利共生和致病成员。我们提出，主要组织相容性复合体 II (MHC) 基因型有助于识别和调节肠道微生物，因此 MHC 多态性有助于宿主间微生物的变异。在这里，我们展示了 MHC IIb 多态性与一种小型鱼类三刺鱼的单一野生脊椎动物种群内肠道微生物群落在个体间的变化有关。我们从温哥华岛的雪松湖采集了棘鱼样本，并使用下一代测序对棘鱼的肠道微生物群（16S 测序）和 MHC 类 IIb 外显子 2 序列进行了基因分型。某些 MHC 基序的存在与某些微生物科的相对丰度（增加或减少）改变有关。这些效应大小适中，涉及少数微生物类群，但这些结果首次表明 MHC 基因型可能会影响自然种群中肠道微生物组成（在少数实验室小鼠的研究中也发现了 MHC-微生物关联）。令人惊讶的是，这些 MHC 效应经常具有性别依赖性。最后，具有更多样化 MHC 基序的宿主具有更少样化的肠道微生物群。一种含义是，MHC 可能会影响治疗与菌群失调相关疾病的治疗策略的效果，包括健康和患病患者之间微生物移植的结果。我们还推测，MHC 驱动的寄生虫选择有可能间接地改变宿主的肠道微生物群，反之亦然。
