Huang Xiaoyun, Johnson April E, Brehm Joshua N, Thanh Do Thi Van, Auchtung Thomas A, McCullough Hugh C, Lerma Armando I, Haidacher Sigmund J, Hoch Kathleen M, Horvath Thomas D, Sorg Joseph A, Haag Anthony M, Auchtung Jennifer M
Department of Food Science and Technology and Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE 68588 USA.
Department of Biology, Texas A&M University, College Station, TX USA.
bioRxiv. 2024 Dec 11:2024.07.17.603937. doi: 10.1101/2024.07.17.603937.
Treatment with antibiotics is a major risk factor for infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit colonization include conversion of conjugated primary bile salts into secondary bile salts toxic to growth, and competition between the microbiota and for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with six clinically-used antibiotics influenced susceptibility to infection in 12 different microbial communities cultivated from healthy individuals. Antibiotic treatment reduced microbial richness; disruption varied by antibiotic class and microbiota composition, but did not correlate with susceptibility. Antibiotic treatment also disrupted microbial bile salt metabolism, increasing levels of the primary bile salt, cholate. However, changes in bile salt did not correlate with increased susceptibility. Further, bile salts were not required to inhibit colonization. We tested whether amino acid fermentation contributed to persistence of in antibiotic-treated communities. mutants unable to use proline as an electron acceptor in Stickland fermentation due to disruption of proline reductase (-) had significantly lower levels of colonization than wild-type strains in four of six antibiotic-treated communities tested. Inability to ferment glycine or leucine as electron acceptors, however, was not sufficient to limit colonization in any communities. This data provides further support for the importance of bile salt-independent mechanisms in regulating colonization of
抗生素治疗是感染的一个主要风险因素，这可能是由于胃肠道微生物群的耗竭所致。两种由微生物群介导的限制定植的机制被认为包括将结合型初级胆汁盐转化为对生长有毒的次级胆汁盐，以及微生物群之间为限制营养物质而进行的竞争。我们使用一个模拟远端结肠营养状况的连续流动模型，研究了六种临床使用的抗生素治疗如何影响从健康个体培养的12种不同微生物群落对感染的易感性。抗生素治疗降低了微生物丰富度；破坏程度因抗生素类别和微生物群组成而异，但与易感性无关。抗生素治疗还扰乱了微生物胆汁盐代谢，增加了初级胆汁盐胆酸盐的水平。然而，胆汁盐的变化与易感性增加无关。此外，抑制定植并不需要胆汁盐。我们测试了氨基酸发酵是否有助于在抗生素处理的群落中持续存在。由于脯氨酸还原酶（-）的破坏而无法在 Stickland 发酵中使用脯氨酸作为电子受体的突变体，在六个测试的抗生素处理群落中的四个中，其定植水平明显低于野生型菌株。然而，无法将甘氨酸或亮氨酸发酵为电子受体不足以在任何群落中限制定植。这些数据进一步支持了胆汁盐非依赖机制在调节定植中的重要性。
