Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites

Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites
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抗生素通过丰富营养物质和消耗微生物代谢产物来促进耐碳青霉烯类肠杆菌科细菌的肠道生长

DOI:
10.1101/2023.03.25.533086
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发表时间:
2023
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Yip A
Yip A
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Yip A

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肠道是碳青霉烯类耐药肠杆菌科(CRE)的主要定植部位,并作为CRE的储存库,导致侵入性感染(例如血流感染)。广谱抗生素破坏肠道微生物群介导的定植抗性,促进肠道内CRE的扩张。在这里,我们表明,益生菌诱导的肠道微生物种群的减少导致营养物质的富集和抑制性代谢产物的消耗,这增强了CRE的生长。抗生素降低了人体粪便微生物群体外培养物中肠道微生物(包括双歧杆菌科和拟杆菌目)的丰度;这伴随着微生物代谢产物的消耗和营养物质的富集。我们测量了几种CRE菌株的营养利用能力、营养偏好和代谢物抑制能力。我们发现,CRE可以使用营养物质(抗生素处理后富集)作为生长的碳源和氮源。这些营养物质在粪便中也会增加,而在肠道定植碳青霉烯类耐药大肠杆菌后会减少。此外,某些微生物代谢物(在抗生素治疗后耗尽)抑制CRE生长。我们的研究结果表明,用抗生素杀死肠道微生物通过丰富营养物质和消耗抑制性微生物代谢产物促进CRE定殖。
The intestine is the primary colonisation site for carbapenem-resistantEnterobacteriaceae(CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (includingBifidobacteriaceaeandBacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistantEscherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites.
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