Department of Surgery, University of Chicago, Chicago, Illinois, USA.
Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
mBio. 2019 Jul 30;10(4):e00903-19. doi: 10.1128/mBio.00903-19.
Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of , a bloom in , and the emergence of antibiotic-resistant organisms among the cecal microbiota. When WD-fed mice were administered antibiotics and subjected to 30% liver resection, lethal sepsis, characterized by multiple-organ damage, developed. Notable was the emergence and systemic dissemination of multidrug-resistant (MDR) pathobionts, including carbapenem-resistant, extended-spectrum β-lactamase-producing , which expressed a virulent and immunosuppressive phenotype. Analysis of the distribution of exact sequence variants belonging to the genus suggested that these strains originated from the cecal mucosa. No mortality or MDR pathogens were observed in identically treated mice fed a standard chow diet. Taken together, these results suggest that consumption of a Western diet and exposure to certain antibiotics may predispose to life-threating postoperative infection associated with MDR organisms present among the gut microbiota. Obesity remains a prevalent and independent risk factor for life-threatening infection following major surgery. Here, we demonstrate that when mice are fed an obesogenic Western diet (WD), they become susceptible to lethal sepsis with multiple organ damage after exposure to antibiotics and an otherwise-recoverable surgical injury. Analysis of the gut microbiota in this model demonstrates that WD alone leads to loss of , a bloom of , and evidence of antibiotic resistance development even before antibiotics are administered. After antibiotics and surgery, lethal sepsis with organ damage developed in in mice fed a WD with the appearance of multidrug-resistant pathogens in the liver, spleen, and blood. The importance of these findings lies in exposing how the selective pressures of diet, antibiotic exposure, and surgical injury can converge on the microbiome, resulting in lethal sepsis and organ damage without the introduction of an exogenous pathogen.
尽管使用了抗生素和无菌技术，术后感染仍然是患者面临的现实且严重的威胁。最近的估计表明，与术后感染相关的病原体中有 50% 对用于预防的标准抗生素产生了耐药性。在这种情况下，确定的风险因素包括肥胖和抗生素暴露。为了研究肥胖和抗生素暴露对术后感染的综合影响，让小鼠在致肥胖的西式饮食（WD）上增重，给予抗生素，然后进行可恢复的无菌手术损伤（30%肝切除术）。单独喂食 WD 会导致盲肠微生物组严重失衡，其特征是多样性降低、减少、增加、以及盲肠微生物组中出现抗生素耐药生物。当 WD 喂养的小鼠给予抗生素并进行 30%肝切除术后，会发展为致命性败血症，其特征是多器官损伤。值得注意的是，多药耐药（MDR）病原体的出现和全身传播，包括耐碳青霉烯类、产超广谱β-内酰胺酶的，表现出毒力和免疫抑制表型。对属于属的精确序列变异体的分布进行分析表明，这些菌株源自盲肠黏膜。在给予相同治疗的喂食标准饲料的小鼠中未观察到死亡率或 MDR 病原体。总之，这些结果表明，食用西式饮食和暴露于某些抗生素可能会使与肠道微生物组中存在的 MDR 生物相关的危及生命的术后感染易于发生。肥胖仍然是大手术后危及生命感染的普遍且独立的危险因素。在这里，我们证明了当小鼠喂食致肥胖的西式饮食（WD）时，它们在接触抗生素和可恢复的手术损伤后易发生致命性败血症，伴有多器官损伤。该模型中肠道微生物组的分析表明，单独 WD 会导致减少，增加，甚至在给予抗生素之前就有抗生素耐药性发展的证据。给予抗生素和手术后，WD 喂养的小鼠出现了致命性败血症，伴有器官损伤，肝脏、脾脏和血液中出现了多药耐药病原体。这些发现的重要性在于揭示了饮食、抗生素暴露和手术损伤的选择压力如何可以集中在微生物组上，导致没有引入外源性病原体的情况下发生致命性败血症和器官损伤。
