Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
Cell Rep. 2024 Aug 27;43(8):114572. doi: 10.1016/j.celrep.2024.114572. Epub 2024 Aug 7.
Antibiotics cause collateral damage to resident microbes that is associated with various health risks. To date, studies have largely focused on the impacts of antibiotics on large intestinal and fecal microbiota. Here, we employ a gastrointestinal (GI) tract-wide integrated multiomic approach to show that amoxicillin (AMX) treatment reduces bacterial abundance, bile salt hydrolase activity, and unconjugated bile acids in the small intestine (SI). Losses of fatty acids (FAs) and increases in acylcarnitines in the large intestine (LI) correspond with spatially distinct expansions of Proteobacteria. Parasutterella excrementihominis engage in FA biosynthesis in the SI, while multiple Klebsiella species employ FA oxidation during expansion in the LI. We subsequently demonstrate that restoration of unconjugated bile acids can mitigate losses of commensals in the LI while also inhibiting the expansion of Proteobacteria during AMX treatment. These results suggest that the depletion of bile acids and lipids may contribute to AMX-induced dysbiosis in the lower GI tract.
抗生素会对常驻微生物造成附带损害，从而带来各种健康风险。迄今为止，研究主要集中在抗生素对大肠和粪便微生物群的影响上。在这里，我们采用胃肠道（GI）广泛的综合多组学方法来表明，阿莫西林（AMX）治疗会降低小肠（SI）中的细菌丰度、胆盐水解酶活性和未结合胆汁酸。大肠（LI）中脂肪酸（FAs）的减少和酰基辅酶 A 的增加与变形菌的空间上明显扩张相对应。粪拟杆菌（Parasutterella excrementihominis）在 SI 中参与 FA 的生物合成，而在 LI 中扩张时，多种克雷伯氏菌（Klebsiella）物种则利用 FA 氧化。随后，我们证明恢复未结合的胆汁酸可以减轻 LI 中共生菌的损失，同时抑制 AMX 治疗期间变形菌的扩张。这些结果表明，胆汁酸和脂质的消耗可能导致 AMX 诱导的下胃肠道菌群失调。
