Gut Microbiota Contributes to Spontaneous Colitis in E3 Ligase Itch-Deficient Mice [MUCOSAL IMMUNOLOGY]

Key Points

  • Spontaneous colitis in Itch-deficient mice is associated with altered gut microbiota.

  • Alterations in gut microbiota are independent of elevated IL-17 in Itch-deficient mice.

  • Bacteroides vulgatus induces colonic inflammation in Itch−/− mice.

Abstract

Inflammatory bowel diseases are associated with complex shifts in microbiota composition. However, it remains unclear whether specific subsets of commensal bacteria induce inflammatory bowel diseases in genetically susceptible hosts. In this study, we found that deficiency of the E3 ligase Itch, which leads to spontaneous colitis and rectal prolapse, is associated with alteration of the gut microbiota. 16S rRNA sequencing showed expansion of colitogenic Bacteroides sp. in Itch−/− mice. Treatment with broad-spectrum antibiotics substantially reduced colonic inflammation in Itch−/− mice. Microbiota of Itch−/− mice failed to induce spontaneous colitis upon transfer to Itch+/+ mice but aggravated chemically induced colitis. Furthermore, we found that Bacteroides vulgatus, which is expanded in Itch−/− mice, was sufficient to induce colon inflammation in Itch−/− mice.

Footnotes

  • This work was supported by grants from the National Institutes of Health (R01-DK115668-01), the Cancer Prevention Research Institute of Texas (RP160577), Baylor Charles A. Sammons Cancer Center and Baylor Scott and White Research Institute–Translational Genomics Research Institute collaborative grants (to K.V.), and Grant R01-DK117001 from the National Institutes of Health (to A.L.T.).

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article:

    DKO
    double knockout
    DSS
    dextran sulfate sodium
    FOB
    fecal occult blood
    IBD
    inflammatory bowel disease
    MMP
    matrix metalloproteinase
    OTU
    operational taxonomic unit
    WT
    wild-type
    ΘYC
    Yue and Clayton.
  • Received October 23, 2017.
  • Accepted February 10, 2020.

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