美国密歇根大学医学院Nobuhiko Kamada研究组发现，白介素22（IL-22）介导的宿主糖基化通过调节肠道菌群的代谢活性来预防艰难梭菌感染（CDI）。这一研究成果在线发表在2020年2月17日的《自然—医学》上。

他们表明由肠道菌群定植诱导的IL-22，对于预防与人类菌群相关的（HMA）小鼠的CDI至关重要。HMA小鼠中的IL-22信号调节宿主糖基化，从而使肠道微生物组中消耗琥珀酸的细菌芽孢杆菌得以生长。

芽孢杆菌减少了琥珀酸内酯的可用性，琥珀酸内酯是艰难梭菌生长的关键代谢产物，因此阻止了艰难梭菌的生长。IL-22介导的宿主N-糖基化可能在溃疡性结肠炎（UC）患者中受损，并使UC-HMA小鼠更容易感染CDI。

健康人源微生物菌群或芽孢杆菌的移植降低了琥珀酸内酯的水平，并恢复了UC-HMA小鼠的定植抗性。因此，IL-22介导的宿主糖基化促进了与艰难梭菌竞争营养位的共生细菌的生长。

据了解，宿主免疫在肠道菌群介导的CDI抵抗中的参与尚不完全清楚。

附：英文原文

Title: Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota

Author: Hiroko Nagao-Kitamoto, Jhansi L. Leslie, Sho Kitamoto, Chunsheng Jin, Kristina A. Thomsson, Merritt G. Gillilland, 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

Issue&Volume: 2020-02-17

Abstract: 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.

DOI: 10.1038/s41591-020-0764-0

Source: https://www.nature.com/articles/s41591-020-0764-0