Zhao Meiqi, Ma Jiajia, Liu Huiru, Luo Ying, Deng Huiting, Wang Dandan, Wang Fengmei, Zhang Peng
School of Medicine, Nankai University, Tianjin 300071, China.
Department of Gastroenterology and Hepatology, Nankai University Affiliated Third Central Hospital, Tianjin 300072, China.
Microorganisms. 2023 Jul 3;11(7):1741. doi: 10.3390/microorganisms11071741.
The gut microbiota, as a major source of opportunistic pathogens, poses a great threat to systemic infection, whereas the role of the gut microbiota in sepsis is underestimated. Here, we aimed to explore the effects of different gut microbiota patterns (namely, enterotypes) in cecal ligation and puncture (CLP)-induced murine sepsis. To achieve this purpose, we built four kinds of enterotypes by exposing mice to different types of antibiotics (azithromycin, amoxicillin, metronidazole, and levofloxacin). The results showed that antibiotic exposure induced different enterotypes, which, in turn, led to varying levels of systemic inflammation in septic mice, with amoxicillin-associated enterotypes exhibiting the most severe inflammation, followed by metronidazole, azithromycin, and levofloxacin. Specifically, the amoxicillin-associated enterotype was characterized by an abundance of intestinal opportunistic pathogens, including Enterobacteriaceae, Sutterellaceae, and Morganellaceae. This enterotype played a significant role in promoting the pathogenic potential of the gut microbiota, ultimately contributing to the development of severe systemic inflammation. Furthermore, the amoxicillin-associated enterotype exaggerated the sepsis-related liver injury, as evidenced by higher levels of alanine aminotransferase, aspartate transaminase, and hepatic malondialdehyde. The results of the RNA sequencing and the fecal suspension intraperitoneal injection sepsis model indicated that the amoxicillin-associated enterotype provoked acute hepatic immune responses and led to more significant metabolic compensation in the event of sepsis. Collectively, we concluded that the gut microbiota was one crucial factor for heterogeneity in sepsis, where the modulated gut microbiota likely prevented or reduced the serious consequences of sepsis, at least in gut-derived sepsis.
肠道微生物群作为机会性病原体的主要来源，对全身感染构成了巨大威胁，而肠道微生物群在脓毒症中的作用却被低估了。在此，我们旨在探究盲肠结扎穿刺（CLP）诱导的小鼠脓毒症中不同肠道微生物群模式（即肠型）的影响。为实现这一目的，我们通过让小鼠接触不同类型的抗生素（阿奇霉素、阿莫西林、甲硝唑和左氧氟沙星）构建了四种肠型。结果表明，抗生素暴露诱导了不同的肠型，进而导致脓毒症小鼠出现不同程度的全身炎症，其中与阿莫西林相关的肠型表现出最严重的炎症，其次是甲硝唑、阿奇霉素和左氧氟沙星。具体而言，与阿莫西林相关的肠型的特征是肠道机会性病原体丰富，包括肠杆菌科、萨特氏菌科和摩根氏菌科。这种肠型在促进肠道微生物群的致病潜力方面发挥了重要作用，最终导致严重全身炎症的发展。此外，与阿莫西林相关的肠型加剧了脓毒症相关的肝损伤，丙氨酸转氨酶、天冬氨酸转氨酶和肝丙二醛水平升高证明了这一点。RNA测序和粪便悬液腹腔注射脓毒症模型的结果表明，与阿莫西林相关的肠型引发了急性肝脏免疫反应，并在脓毒症发生时导致更显著的代谢补偿。总体而言，我们得出结论，肠道微生物群是脓毒症异质性的一个关键因素，其中经调节的肠道微生物群可能预防或减轻脓毒症的严重后果，至少在肠道源性脓毒症中如此。
