Abstract & Authors:展开
The involvement of host immunity in the gut microbiota-mediated colonization resistance to Clostridioides difficile infection (CDI) is incompletely understood. Here, we show that interleukin (IL)-22, induced by colonization of the gut microbiota, is crucial for the prevention of CDI in human microbiota-associated (HMA) mice. IL-22 signaling in HMA mice regulated host glycosylation, which enabled the growth of succinate-consuming bacteria Phascolarctobacterium spp. within the gut microbiome. Phascolarctobacterium reduced the availability of luminal succinate, a crucial metabolite for the growth of C. difficile, and therefore prevented the growth of C. difficile. IL-22-mediated host N-glycosylation is likely impaired in patients with ulcerative colitis (UC) and renders UC-HMA mice more susceptible to CDI. Transplantation of healthy human-derived microbiota or Phascolarctobacterium reduced luminal succinate levels and restored colonization resistance in UC-HMA mice. IL-22-mediated host glycosylation thus fosters the growth of commensal bacteria that compete with C. difficile for the nutritional niche.
Hiroko Nagao-Kitamoto,Jhansi L Leslie,Sho Kitamoto,Chunsheng Jin,Kristina A Thomsson,Merritt G Gillilland III,Peter Kuffa,Yoshiyuki Goto,Robert R Jenq,Chiharu Ishii,Akiyoshi Hirayama,Anna M Seekatz,Eric C Martens,Kathryn A Eaton,John Y Kao,Shinji Fukuda,Peter D R Higgins,Niclas G Karlsson,Vincent B Young,Nobuhiko Kamada