Regulatory Biology Laboratory, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
Division of Gastroenterology, University of California, San Diego, 9500 Gilman Drive, MC 0983, La Jolla, CA, 92093-0983, USA.
Nat Commun. 2018 Jul 20;9(1):2872. doi: 10.1038/s41467-018-05336-9.
Antibiotic-induced microbiome depletion (AIMD) has been used frequently to study the role of the gut microbiome in pathological conditions. However, unlike germ-free mice, the effects of AIMD on host metabolism remain incompletely understood. Here we show the effects of AIMD to elucidate its effects on gut homeostasis, luminal signaling, and metabolism. We demonstrate that AIMD, which decreases luminal Firmicutes and Bacteroidetes species, decreases baseline serum glucose levels, reduces glucose surge in a tolerance test, and improves insulin sensitivity without altering adiposity. These changes occur in the setting of decreased luminal short-chain fatty acids (SCFAs), especially butyrate, and the secondary bile acid pool, which affects whole-body bile acid metabolism. In mice, AIMD alters cecal gene expression and gut glucagon-like peptide 1 signaling. Extensive tissue remodeling and decreased availability of SCFAs shift colonocyte metabolism toward glucose utilization. We suggest that AIMD alters glucose homeostasis by potentially shifting colonocyte energy utilization from SCFAs to glucose.
抗生素诱导的微生物组耗竭（AIMD）已被广泛用于研究肠道微生物组在病理条件下的作用。然而，与无菌小鼠不同，AIMD 对宿主代谢的影响仍不完全清楚。在这里，我们展示了 AIMD 的作用，以阐明其对肠道内稳态、腔内分泌信号和代谢的影响。我们证明，AIMD 减少了腔Firmicutes 和 Bacteroidetes 物种，降低了基础血清葡萄糖水平，减少了耐量试验中的葡萄糖激增，并提高了胰岛素敏感性，而不改变肥胖。这些变化发生在腔短链脂肪酸（SCFA），特别是丁酸盐和次级胆汁酸池减少的情况下，这影响了全身胆汁酸代谢。在小鼠中，AIMD 改变了盲肠的基因表达和肠道胰高血糖素样肽 1 信号。广泛的组织重塑和 SCFA 的减少使结肠细胞代谢转向葡萄糖利用。我们认为，AIMD 通过可能将结肠细胞的能量利用从 SCFA 转移到葡萄糖来改变葡萄糖稳态。
