Reprogrammed and transmissible intestinal microbiota confer diminished susceptibility to induced colitis in TMF-/- mice

Shai Bel, Yoav Elkis, Hila Elifantz, Omry Koren, Rotem Ben-Hamo, Tal Lerer-Goldshtein, Roni Rahimi, Shomron Ben Horin, Abraham Nyska, Sally Shpungin, Uri Nir

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Tata Element Modulatory Factor (TMF/ARA160) is a multifunctional Golgi-associated protein, which accumulates in colonic enterocytes and goblet cells. Mice lacking TMF/ARA160 (TMF-/-) produce thick and uniform colonic mucus that resists adherent bacterial colonization and diminishes susceptibility of these mice to induced acute colitis, through a mechanism that is not fully understood. Here, we show that mucus secretion by goblet cells is altered in the colon of TMF-/- mice, resulting in the formation of a highly oligomerized colonic gel-forming mucin, MUC2. Microbiome analysis revealed a shift in the microbiota of TMF-/- mice leading to predominance of the Firmicutes phylum and a significantly higher abundance of probiotic beneficial bacterial species. Notably, this trait was transmissible, and when cohoused with wild-type animals, TMF-/- mice influenced the microbiota and diminished the susceptibility of wildtype mice to chemically induced dextran sulfate sodium colitis. Thus, altered mucus secretion in TMF-/- mouse colons is accompanied by a reprogrammed intestinal microbiota, leading to a transmissible reduced sensitivity to induced colitis.

Original languageEnglish
Pages (from-to)4964-4969
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number13
DOIs
StatePublished - 1 Apr 2014

Keywords

  • Co-housing
  • Inflammatory bowel disease
  • Mucus granule

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