Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
Division of Infectious Diseases/Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
Sci Rep. 2019 Jan 29;9(1):885. doi: 10.1038/s41598-018-37547-x.
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.
许多艰难梭菌感染（CDI）病例对标准抗生素治疗策略反应不佳，并且患者经常遭受复发性感染，其特征是严重腹泻。我们的小组之前曾报道过使用标准化粪便衍生微生物生态治疗（MET-1）成功治愈了两名复发性 CDI 患者。我们使用支持细菌群落的远端肠道体外模型，对源自健康供体粪便的两个定义微生物生态系统（DEC58 和亚群社区 MET-1）以及代表生态失调状态的生态系统（环丙沙星处理的 DEC58）的代谢物谱进行了特征描述。然后，评估了两种艰难梭菌菌株对生态系统衍生成分的生长和毒力决定因素的反应。与环丙沙星处理的 DEC58 代谢物相比，用 DEC58 代谢物处理时 CD186（基因型 027）和 CD973（基因型 078）的生长减少。此外，与单独用 DEC58 耗尽的培养基处理相比，用环丙沙星处理的 DEC58 耗尽的培养基处理后 CD186 TcdA 和 TcdB 的分泌增加。尽管在两种研究的菌株中，有几个代谢物水平存在差异，但对定义的微生物生态系统的耗尽培养基的反应也调节了艰难梭菌的净代谢产物。进一步研究这些拮抗特性将有助于开发用于 CDI 的基于微生物组的治疗方法。
