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

doi:10.1038/s41591-020-0764-0

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

Genomic Medicine

Research output: Contribution to journal › Article › peer-review

130 Scopus citations

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.

Original language	English (US)
Pages (from-to)	608-617
Number of pages	10
Journal	Nature medicine
Volume	26
Issue number	4
DOIs	https://doi.org/10.1038/s41591-020-0764-0
State	Published - Apr 1 2020

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

MD Anderson CCSG core facilities

Microbiome Facility

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10.1038/s41591-020-0764-0

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Nagao-Kitamoto, H., Leslie, J. L., Kitamoto, S., Jin, C., Thomsson, K. A., Gillilland, M. G., Kuffa, P., Goto, Y., Jenq, R. R., Ishii, C., Hirayama, A., Seekatz, A. M., Martens, E. C., Eaton, K. A., Kao, J. Y., Fukuda, S., Higgins, P. D. R., Karlsson, N. G., Young, V. B., & Kamada, N. (2020). Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota. Nature medicine, 26(4), 608-617. https://doi.org/10.1038/s41591-020-0764-0

Nagao-Kitamoto, H, Leslie, JL, Kitamoto, S, Jin, C, Thomsson, KA, Gillilland, MG, Kuffa, P, Goto, Y, Jenq, RR, Ishii, C, Hirayama, A, Seekatz, AM, Martens, EC, Eaton, KA, Kao, JY, Fukuda, S, Higgins, PDR, Karlsson, NG, Young, VB & Kamada, N 2020, 'Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota', Nature medicine, vol. 26, no. 4, pp. 608-617. https://doi.org/10.1038/s41591-020-0764-0

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

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.",

author = "Hiroko Nagao-Kitamoto and Leslie, {Jhansi L.} and Sho Kitamoto and Chunsheng Jin and Thomsson, {Kristina A.} and Gillilland, {Merritt G.} and Peter Kuffa and Yoshiyuki Goto and Jenq, {Robert R.} and Chiharu Ishii and Akiyoshi Hirayama and Seekatz, {Anna M.} and Martens, {Eric C.} and Eaton, {Kathryn A.} and Kao, {John Y.} and Shinji Fukuda and Higgins, {Peter D.R.} and Karlsson, {Niclas G.} and Young, {Vincent B.} and Nobuhiko Kamada",

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AU - Leslie, Jhansi L.

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AU - Jin, Chunsheng

AU - Thomsson, Kristina A.

AU - Gillilland, Merritt G.

AU - Kuffa, Peter

AU - Goto, Yoshiyuki

AU - Jenq, Robert R.

AU - Ishii, Chiharu

AU - Hirayama, Akiyoshi

AU - Seekatz, Anna M.

AU - Martens, Eric C.

AU - Eaton, Kathryn A.

AU - Kao, John Y.

AU - Fukuda, Shinji

AU - Higgins, Peter D.R.

AU - Karlsson, Niclas G.

AU - Young, Vincent B.

AU - Kamada, Nobuhiko

PY - 2020/4/1

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N2 - 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.

AB - 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.

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

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MD Anderson CCSG core facilities

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