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

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Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota
Nature Medicine ( IF 82.9 ) Pub Date : 2020-02-17 , DOI: 10.1038/s41591-020-0764-0
Hiroko Nagao-Kitamoto ₁ , Jhansi L Leslie _{2,

3,

4} , Sho Kitamoto ₁ , Chunsheng Jin ₅ , Kristina A Thomsson ₅ , Merritt G Gillilland ₁ , Peter Kuffa ₁ , Yoshiyuki Goto _{6,

7,

8} , Robert R Jenq ₉ , Chiharu Ishii ₁₀ , Akiyoshi Hirayama ₁₀ , Anna M Seekatz _{2,

11} , Eric C Martens ₃ , Kathryn A Eaton ₃ , John Y Kao ₁ , Shinji Fukuda _{10,

12,

13,

14} , Peter D R Higgins ₁ , Niclas G Karlsson ₅ , Vincent B Young _{2,

3} , Nobuhiko Kamada ₁

Affiliation

Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI, USA.
Division of Infectious Disease, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
The University of Virginia, Washington, VA, USA.
Institute of Biomedicine, Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan.
Division of Mucosal Symbiosis, International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
AMED-PRIME, Japan Agency for Medical Research and Development, Tokyo, Japan.
Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston TX, USA.
Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan.
Clemson University, Columbia, SC, USA.
Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Ebina, Japan.
Transborder Medical Research Center, University of Tsukuba, Tsukuba, Japan.
PRESTO, Japan Science and Technology Agency, Kawaguchi, Japan.

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.

中文翻译：

白细胞介素 22 介导的宿主糖基化通过调节肠道微生物群的代谢活动预防艰难梭菌感染

宿主免疫参与肠道菌群介导的艰难梭菌感染 (CDI) 的定植抗性尚不完全清楚。在这里，我们表明由肠道菌群定植诱导的白细胞介素 (IL)-22 对于预防人类微生物群相关 (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，从而促进消耗琥珀酸的细菌考拉杆菌属的生长。在肠道微生物组内。考拉杆菌降低了管腔琥珀酸盐的可用性，这是一种对艰难梭菌生长至关重要的代谢产物，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。移植健康的人源微生物群或考拉杆菌降低了 UC-HMA 小鼠的管腔琥珀酸盐水平并恢复了定植抗性。因此，IL-22 介导的宿主糖基化促进了与艰难梭菌竞争营养生态位的共生细菌的生长。

更新日期：2020-02-17

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