State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Research Units of Discovery of Unknown Bacteria and Function (2018RU010), Chinese Academy of Medical Sciences, Beijing, 102206, China.
State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Research Units of Discovery of Unknown Bacteria and Function (2018RU010), Chinese Academy of Medical Sciences, Beijing, 102206, China; Shunyi District Center for Disease Control and Prevention, Beijing, China.
Biomed Pharmacother. 2021 May;137:111290. doi: 10.1016/j.biopha.2021.111290. Epub 2021 Jan 25.
Clostridioides difficile infection (CDI) is a growing global public health threat. While fecal microbiota transplantation (FMT) is an effective therapy for CDI, a number of challenges limit its application. Studies suggest that probiotics may be a promising alternative therapy. In the current study, we evaluated whether Bacteroides thetaiotaomicron (B. thetaiotaomicron) would inhibit colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. We found that B. thetaiotaomicron administration decreased the copies of C. difficile and inhibited inflammation in the colon. 16S rRNA sequencing showed that B. thetaiotaomicron administration was associated with a significantly increased relative abundance of Bacteroidetes and decreased level of Proteobacteria, leading to the reversal of the effect of antibiotics treatment and C. difficile infection on microbiota. B. thetaiotaomicron administration was associated with increases in the concentrations of alpha-muricholic acid, beta-muricholic acid, 12 ketolithocholic acid, and deoxycholic acid which are known to inhibit the growth of C. difficile, as well as reductions in the level of taurocholic acid, which promotes germination of C. difficile. Altered profile of major high abundance bile acids by B. thetaiotaomicron administration was similar to that with FMT treatment. Based on these results, we proposed the concept of "the ratio of promotion/inhibition BAs" which would advance our understanding of the relation of C. difficile and BAs.
艰难梭菌感染（CDI）是一个日益严重的全球公共卫生威胁。粪菌移植（FMT）是治疗 CDI 的有效方法，但存在许多限制其应用的挑战。研究表明，益生菌可能是一种有前途的替代治疗方法。在本研究中，我们评估了拟杆菌属（Bacteroides thetaiotaomicron，B. thetaiotaomicron）是否会抑制产毒 BI/NAP1/027 艰难梭菌在小鼠模型中的定植。我们发现，B. thetaiotaomicron 的给药减少了艰难梭菌的拷贝数，并抑制了结肠的炎症。16S rRNA 测序显示，B. thetaiotaomicron 的给药与厚壁菌门的相对丰度显著增加和变形菌门的水平降低有关，导致抗生素治疗和艰难梭菌感染对微生物群的作用发生逆转。B. thetaiotaomicron 的给药与α-鼠胆酸、β-鼠胆酸、12-酮石胆酸和脱氧胆酸浓度的增加有关，这些酸已知可抑制艰难梭菌的生长，同时与胆酸浓度的降低有关，后者可促进艰难梭菌的发芽。B. thetaiotaomicron 给药引起的主要高丰度胆汁酸的特征谱与 FMT 治疗相似。基于这些结果，我们提出了“促进/抑制胆汁酸的比值”的概念，这将有助于我们理解艰难梭菌和胆汁酸之间的关系。
