ABSTRACT

Studies identifying bacterial members that dictate host phenotype have focused mainly on the dominant members, and the role of low abundance microbes in determining host phenotypes and pathogenesis of diseases remains unexplored. In this study, we compared the gut bacterial community of mice with wide-ranging microbial exposure to determine if low abundance bacteria vary based on microbial exposure or remain consistent. We noted that similar to the high abundance bacterial community, a core community of low abundance bacteria made up a significant portion of the gut microbiome irrespective of microbial exposure. To determine the role of low abundance bacteria in regulating community composition and host gene expression, we devised a microbiome dilution strategy to “delete” out low abundance bacteria and engrafted the diluted microbiomes into germ-free mice. Our approach successfully excluded low abundance bacteria from small and large intestinal bacterial communities and induced global changes in microbial community composition in the large intestine. Gene expression analysis of intestinal tissue revealed that loss of low abundance bacteria resulted in a drastic reduction in expression of multiple genes involved MHCII antigen presentation pathway and T-cell cytokine production in the small intestine. The effect of low abundance bacteria on MHCII expression was found to be specific to the intestinal epithelium at an early timepoint post-colonization and correlated with bacteria belonging to the family Erysipelotrichaceae. We conclude that low abundance bacteria have a significantly higher immuno-stimulatory effect compared to dominant bacteria and are thus potent drivers of early immune education in the gut.

 抽象的

鉴定决定宿主表型的细菌成员的研究主要集中在主要成员上，而低丰度微生物在确定宿主表型和疾病发病机制中的作用仍有待探索。在这项研究中，我们比较了具有广泛微生物暴露的小鼠的肠道细菌群落，以确定低丰度细菌是否根据微生物暴露而变化或保持一致。我们注意到，与高丰度细菌群落类似，低丰度细菌的核心群落构成了肠道微生物组的很大一部分，无论微生物暴露如何。为了确定低丰度细菌在调节群落组成和宿主基因表达中的作用，我们设计了一种微生物组稀释策略来“删除”低丰度细菌，并将稀释的微生物组移植到无菌小鼠体内。我们的方法成功地排除了小肠和大肠细菌群落中的低丰度细菌，并诱导大肠微生物群落组成的整体变化。肠道组织的基因表达分析表明，低丰度细菌的损失导致小肠中涉及 MHCII 抗原呈递途径和 T 细胞细胞因子产生的多个基因的表达急剧减少。发现低丰度细菌对 MHCII 表达的影响在定植后的早期时间点对肠上皮具有特异性，并且与属于丹毒科的细菌相关。我们的结论是，与优势细菌相比，低丰度细菌具有显着更高的免疫刺激作用，因此是肠道早期免疫教育的有力驱动力。