title: Reprogrammed and transmissible intestinal microbiota confer diminished susceptibility to induced colitis in TMF-/- mice.
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 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.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences and Quaresa Institute for Cancer Research, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Shai
authors.initials: S
authors.lastname: Bel
authors.forename: Yoav
authors.initials: Y
authors.lastname: Elkis
authors.forename: Hila
authors.initials: H
authors.lastname: Elifantz
authors.forename: Omry
authors.initials: O
authors.lastname: Koren
authors.forename: Rotem
authors.initials: R
authors.lastname: Ben-Hamo
authors.forename: Tal
authors.initials: T
authors.lastname: Lerer-Goldshtein
authors.forename: Roni
authors.initials: R
authors.lastname: Rahimi
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben Horin
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.forename: Sally
authors.initials: S
authors.lastname: Shpungin
authors.forename: Uri
authors.initials: U
authors.lastname: Nir
mesh_terms: D000818:Animals; D048430:Cell Shape; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology* / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004268:DNA-Binding Proteins; D004198:Disease Susceptibility / Q000382:microbiology / Q000473:pathology; D005243:Feces / Q000382:microbiology; D000077614:Golgi Matrix Proteins; D007422:Intestines / Q000382:microbiology* / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota; D055262:Mucin-2 / Q000378:metabolism; D009093:Mucus / Q000378:metabolism; D055503:Protein Multimerization; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency* / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000172:deficiency* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D000077614:Golgi Matrix Proteins; D055262:Mucin-2; C554202:Tmf1 protein, mouse; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D044767:Ubiquitin-Protein Ligases
keywords: co-housing; inflammatory bowel disease; mucus granule