Bacterial and host fucosylation maintain IgA homeostasis to limit intestinal inflammation in mice.

Inflammatory bowel disease is associated with several genetic risk loci. Loss-of-function mutation in the α1,2-fucosyltransferase (fut2) gene, which alters fucosylation on the surface of intestinal epithelial cells, is one example. However, whether bacterial fucosylation can contribute to gut inflammation is unclear. Here we show that host fucosylation status influences fucosylation biosynthesis by gut commensal bacteria. Mice colonized with faecal microbiota of Fut2 knockout mice or Bacteroides fragilis with lower surface fucosylation are predisposed to colitis. This was supported by human cohort data showing that bacterial fucosylation levels decrease in patients with inflammatory bowel disease and correlate with intestinal inflammation. Using a mouse model for Bacteroides fragilis to explore the role of fucosylation in gut immunity, we show that the fucosylation status of epithelial cells and bacteria is critical for maintaining B cell responses in the gut. Host-derived and dietary fucose mediate immunoglobulin A (IgA) recognition of gut microbiota, and this interaction facilitates the translocation of commensals to Peyer's patches and alters the immune landscape of Peyer's patches with increased germinal centre B cells and IgA-secreting antigen-specific B cells. Finally, dietary fucose enhances the IgA response against Salmonella and protects against systemic bacterial dissemination. This highlights the role of host and bacterial fucosylation in maintaining IgA homeostasis and immune escape mechanisms.