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

Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4964-9. doi: 10.1073/pnas.1319114111. Epub 2014 Mar 17.


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 wild-type 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.

Keywords: co-housing; inflammatory bowel disease; mucus granule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Shape
  • Colitis / chemically induced
  • Colitis / microbiology*
  • Colitis / pathology*
  • Colon / metabolism
  • Colon / pathology
  • Colon / ultrastructure
  • DNA-Binding Proteins
  • Disease Susceptibility / microbiology
  • Disease Susceptibility / pathology
  • Feces / microbiology
  • Golgi Matrix Proteins
  • Intestines / microbiology*
  • Intestines / pathology*
  • Intestines / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota*
  • Mucin-2 / metabolism
  • Mucus / metabolism
  • Protein Multimerization
  • Transcription Factors
  • Ubiquitin-Protein Ligases / deficiency*
  • Ubiquitin-Protein Ligases / metabolism
  • Vesicular Transport Proteins / deficiency*
  • Vesicular Transport Proteins / metabolism


  • DNA-Binding Proteins
  • Golgi Matrix Proteins
  • Mucin-2
  • Tmf1 protein, mouse
  • Transcription Factors
  • Vesicular Transport Proteins
  • Ubiquitin-Protein Ligases