Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota
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 microbi...
Gespeichert in:
Veröffentlicht in: | Nature medicine 2020-04, Vol.26 (4), p.608-617 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | 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.
In germ-free mice colonized with human microbiota, mucosal IL-22 signaling promotes the growth of succinate-consuming commensal bacteria via host mucus glycosylation, and transplantation of these bacteria limits
Clostridioides difficile
infection. |
---|---|
ISSN: | 1078-8956 1546-170X |
DOI: | 10.1038/s41591-020-0764-0 |