Dietary composition and antibiotic use have major impacts on the structure and function of the gut microbiome, often resulting in dysbiosis. Despite this, little research has been done to explore the role of host diet as a determinant of antibiotic-induced microbiome disruption. Here, we utilize a multi-omic approach to characterize the impact of Western-style diet consumption on ciprofloxacin-induced changes to gut microbiome structure and transcriptional activity. We found that Western diet consumption dramatically increased Bacteroides abundances and shifted the community toward the metabolism of simple sugars and mucus glycoproteins. Mice consuming a Western-style diet experienced a greater expansion of Firmicutes following ciprofloxacin treatment than those eating a control diet. Transcriptionally, we found that ciprofloxacin reduced the abundance of tricarboxylic acid (TCA) cycle transcripts on both diets, suggesting that carbon metabolism plays a key role in the response of the gut microbiome to this antibiotic. Despite this, we observed extensive diet-dependent differences in the impact of ciprofloxacin on microbiota function. In particular, at the whole-community level we detected an increase in starch degradation, glycolysis, and pyruvate fermentation following antibiotic treatment in mice on the Western diet, which we did not observe in mice on the control diet. Similarly, we observed diet-specific changes in the transcriptional activity of two important commensal bacteria, Akkermansia muciniphila and Bacteroides thetaiotaomicron, involving diverse cellular processes such as nutrient acquisition, stress responses, and capsular polysaccharide (CPS) biosynthesis. These findings demonstrate that host diet plays a role in determining the impacts of ciprofloxacin on microbiome composition and microbiome function.

中文翻译：

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西式饮食的消耗调节小鼠肠道微生物群对环丙沙星的反应。

膳食成分和抗生素的使用对肠道微生物组的结构和功能有重大影响，通常会导致菌群失调。尽管如此，很少有研究来探索宿主饮食作为抗生素引起的微生物组破坏的决定因素的作用。在这里，我们利用多组学方法来表征西式饮食消费对环丙沙星诱导的肠道微生物组结构和转录活性变化的影响。我们发现，西方饮食的消耗极大地增加了拟杆菌的丰度，并使群落转向单糖和粘液糖蛋白的代谢。与食用对照饮食的小鼠相比，采用西式饮食的小鼠在环丙沙星治疗后经历了更大的厚壁菌门扩张。在转录方面，我们发现环丙沙星降低了两种饮食中三羧酸（TCA）循环转录本的丰度，这表明碳代谢在肠道微生物群对这种抗生素的反应中起着关键作用。尽管如此，我们观察到环丙沙星对微生物群功能的影响存在广泛的饮食依赖性差异。特别是，在整个群落水平上，我们检测到西方饮食的小鼠接受抗生素治疗后淀粉降解、糖酵解和丙酮酸发酵增加，而我们在对照饮食的小鼠中没有观察到这种情况。同样，我们观察到两种重要共生细菌（ Akkermansia muciniphila和Bacteroides thetaiotaomicron）转录活性的饮食特异性变化，涉及多种细胞过程，如营养获取、应激反应和荚膜多糖 (CPS) 生物合成。这些发现表明，宿主饮食在确定环丙沙星对微生物组组成和微生物组功能的影响方面发挥着重要作用。