Effects of defined gut microbial ecosystem components on virulence determinants of Clostridioides difficile
Effects of defined gut microbial ecosystem components on virulence determinants of Clostridioides difficile
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DOI：
10.1038/s41598-018-37547-x
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发表时间：
2019-01-29
影响因子：
4.6
通讯作者：
Allen-Vercoe, Emma
中科院分区：
文献类型：
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作者：
Carlucci, Christian;Jones, Carys S.;Allen-Vercoe, Emma
许多艰难梭菌感染（CDI）的病例对标准抗生素治疗策略的反应很差，并且患者通常患有以严重腹泻为特征的复发性感染。我们的研究小组先前报道了使用标准化粪便来源的微生物生态系统治疗剂（MET-1）成功治愈2例复发性CDI患者。使用远端肠道的体外模型来支持细菌群落，我们表征了来自健康供体粪便的两种定义的微生物生态系统（DEC 58和亚群群落MET-1）以及代表生态系统的生态系统（环丙沙星处理的DEC 58）的代谢产物谱。研究了两株C.然后评估艰难梭菌菌株对来自生态系统的组分的反应。与环丙沙星处理的DEC 58代谢物相比，DEC 58代谢物处理后CD 186（核糖型027）和CD 973（核糖型078）生长减少。此外，与单独的DEC 58用培养基相比，用环丙沙星处理的DEC 58用培养基处理后，CD 186 TcdA和TcdB分泌增加。C.艰难梭菌也被调节以响应来自确定的微生物生态系统的用过的培养基，尽管几种代谢物水平在所检查的两种菌株中是不同的。对这些拮抗特性的进一步研究将指导基于微生物的CDI疗法的开发。
Many cases of Clostridioides difficile infection (CDI) are poorly responsive to standard antibiotic treatment strategies, and often patients suffer from recurrent infections characterized by severe diarrhea. Our group previously reported the successful cure of two patients with recurrent CDI using a standardized stool-derived microbial ecosystem therapeutic (MET-1). Using an in vitro model of the distal gut to support bacterial communities, we characterized the metabolite profiles of two defined microbial ecosystems derived from healthy donor stool (DEC58, and a subset community, MET-1), as well as an ecosystem representative of a dysbiotic state (ciprofloxacin-treated DEC58). The growth and virulence determinants of two C. difficile strains were then assessed in response to components derived from the ecosystems. CD186 (ribotype 027) and CD973 (ribotype 078) growth was decreased upon treatment with DEC58 metabolites compared to ciprofloxacin-treated DEC58 metabolites. Furthermore, CD186 TcdA and TcdB secretion was increased following treatment with ciprofloxacin-treated DEC58 spent medium compared to DEC58 spent medium alone. The net metabolic output of C. difficile was also modulated in response to spent media from defined microbial ecosystems, although several metabolite levels were divergent across the two strains examined. Further investigation of these antagonistic properties will guide the development of microbiota-based therapeutics for CDI.