Interactions between host and intestinal crypt-resided biofilms are controlled by epithelial fucosylation
Xue-Kun Guo,
Jiali Wang,
Vincent P. van Hensbergen,
Jintao Liu,
Huji Xu,
Xiaoyu Hu
Affiliations
Xue-Kun Guo
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing 100084, China; Corresponding author
Jiali Wang
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing 100084, China
Vincent P. van Hensbergen
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing 100084, China
Jintao Liu
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing 10084, China
Huji Xu
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; School of Clinical Medicine and School of Medicine, Tsinghua University, Beijing 100084, China; Department of Rheumatology and Immunology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; Corresponding author
Xiaoyu Hu
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing 100084, China; Corresponding author
Summary: As highly organized consortia of bacteria, biofilms have long been implicated in aggravating inflammation. However, our understanding regarding in vivo host-biofilm interactions in the complex tissue environments remains limited. Here, we show a unique pattern of crypt occupation by mucus-associated biofilms during the early stage of colitis, which is genetically dependent on bacterial biofilm-forming capacity and restricted by host epithelial α1,2-fucosylation. α1,2-Fucosylation deficiency leads to markedly augmented crypt occupation by biofilms originated from pathogenic Salmonella Typhimurium or indigenous Escherichia coli, resulting in exacerbated intestinal inflammation. Mechanistically, α1,2-fucosylation-mediated restriction of biofilms relies on interactions between bacteria and liberated fucose from biofilm-occupied mucus. Fucose represses biofilm formation and biofilm-related genes in vitro and in vivo. Finally, fucose administration ameliorates experimental colitis, suggesting therapeutic potential of fucose for biofilm-related disorders. This work illustrates host-biofilm interactions during gut inflammation and identifies fucosylation as a physiological strategy for restraining biofilm formation.
