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

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

研究成果: Article査読

55 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)608-617
ページ数10
ジャーナルNature medicine
26
4
DOI
出版ステータスPublished - 2020 4月 1

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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