The drug acarbose is used to treat diabetes, and, by inhibiting α-amylase in the small intestine, increases the amount of starch entering the lower digestive tract. This results in changes to the composition of the microbiota and their fermentation products. Acarbose also increases longevity in mice, an effect that has been correlated with increased production of the short-chain fatty acids propionate and butyrate. In experiments replicated across three study sites, two distantly related species in the bacterial family Muribaculaceae were dramatically more abundant in acarbose-treated mice, distinguishing these responders from other members of the family. Bacteria in the family Muribaculaceae are predicted to produce propionate as a fermentation end product and are abundant and diverse in the guts of mice, although few isolates are available. We reconstructed genomes from metagenomes (MAGs) for nine populations of Muribaculaceae to examine factors that distinguish species that respond positively to acarbose. We found two closely related MAGs (B1A and B1B) from one responsive species that both contain a polysaccharide utilization locus with a predicted extracellular α-amylase. These genomes also shared a periplasmic neopullulanase with another, distantly related MAG (B2) representative of the only other responsive species. This gene differentiated these three MAGs from MAGs representative of non-responding species. Differential gene content in B1A and B1B may be associated with the inconsistent response of this species to acarbose across study sites. This work demonstrates the utility of culture-free genomics for inferring the ecological roles of gut bacteria including their response to pharmaceutical perturbations.

中文翻译：

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从宏基因组组装的 Muribaculaceae 基因组表明小鼠对阿卡波糖治疗的不同反应的遗传驱动因素

药物阿卡波糖用于治疗糖尿病，并通过抑制小肠中的 α-淀粉酶，增加进入下消化道的淀粉量。这会导致微生物群及其发酵产物的组成发生变化。阿卡波糖还能延长小鼠的寿命，这一效应与丙酸和丁酸短链脂肪酸的产量增加有关。在三个研究地点重复的实验中，细菌家族Muribaculaceae中的两个远亲物种在阿卡波糖治疗的小鼠中显着更多，从而将这些反应者与该家族的其他成员区分开来。Muribaculaceae 中的细菌预计会产生丙酸作为发酵终产物，并且在小鼠肠道中含量丰富且多样，尽管可用的分离株很少。我们从九个Muribaculaceae种群的宏基因组 (MAG) 重建基因组检查区分对阿卡波糖有积极反应的物种的因素。我们从一个响应物种中发现了两个密切相关的 MAG（B1A 和 B1B），它们都包含多糖利用位点和预测的细胞外 α-淀粉酶。这些基因组还与另一个代表唯一其他响应物种的远亲 MAG (B2) 共享周质新支链淀粉酶。该基因将这三种 MAG 与代表无反应物种的 MAG 区分开来。B1A 和 B1B 中的差异基因含量可能与该物种在整个研究地点对阿卡波糖的反应不一致有关。这项工作证明了无培养基因组学可用于推断肠道细菌的生态作用，包括它们对药物干扰的反应。