State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Appl Microbiol Biotechnol. 2022 Oct;106(19-20):6689-6700. doi: 10.1007/s00253-022-12154-z. Epub 2022 Sep 10.
Vancomycin is the preferred treatment for Clostridioides difficile infection (CDI) but has been associated with a high recurrence rate of CDI in treated patients. Fecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent CDI (rCDI). Herein, we present a mouse model of CDI to further define the changes in intestinal inflammation, flora, and metabolites following FMT versus vancomycin treatment and to find the potential therapy to restore colonization resistance. Both FMT and vancomycin treatment could ameliorate CDI-induced clinical features and intestinal tissue damage, with decrease in the levels of inflammatory mediators like IL-1β, IL-6, TNF-α, G-CSF, and MCP-1 in the colon and plasma. Observing the fecal gut microbiome profile revealed that unlike vancomycin, FMT could replenish intestinal microbiota by augmenting the relative abundance of the phylum Bacteroidetes and eliminating the abundance of the phylum Proteobacteria. FMT also reduced the levels of several carbohydrates, such as raffinose and fructose-6-phosphate, and amino acids, including tryptophan and glutamyl-valine, in the gut metabolome, thus suppressing C. difficile germination and growth. Our results suggest that the FMT-induced reconstruction of a specific gut community structure and restoration of metabolites promote the recovery of colonization resistance in mice better than vancomycin, thus offering new insights for the prevention of rCDI. KEY POINTS: • Both FMT and vancomycin ameliorate CDI-induced inflammatory response. • FMT restores a specific community structure and gut metabolites. • Mice treated with FMT may promote the recovery of colonization resistance and has a better outcome.
万古霉素是治疗艰难梭菌感染（CDI）的首选药物，但与治疗患者中 CDI 的高复发率有关。粪便微生物群移植（FMT）已成为复发性 CDI（rCDI）的一种非常成功的治疗方法。在此，我们提出了一种 CDI 小鼠模型，以进一步定义 FMT 与万古霉素治疗后肠道炎症、菌群和代谢物的变化，并寻找恢复定植抵抗的潜在治疗方法。FMT 和万古霉素治疗均可改善 CDI 诱导的临床特征和肠道组织损伤，降低结肠和血浆中炎症介质（如 IL-1β、IL-6、TNF-α、G-CSF 和 MCP-1）的水平。观察粪便肠道微生物组谱发现，与万古霉素不同，FMT 通过增加厚壁菌门的相对丰度和消除变形菌门的丰度来补充肠道微生物群。FMT 还降低了肠道代谢组中几种碳水化合物（如棉子糖和果糖-6-磷酸）和几种氨基酸（如色氨酸和谷氨酰缬氨酸）的水平，从而抑制艰难梭菌的发芽和生长。我们的结果表明，FMT 诱导的特定肠道群落结构重建和代谢物恢复可促进小鼠定植抵抗的恢复，优于万古霉素，从而为预防 rCDI 提供了新的见解。
FMT 和万古霉素均可改善 CDI 诱导的炎症反应。
FMT 恢复了特定的群落结构和肠道代谢物。
接受 FMT 治疗的小鼠可能会促进定植抵抗的恢复，并获得更好的效果。
