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

被引:43
作者
Bel, Shai [1 ]
Elkis, Yoav [1 ]
Elifantz, Hila [1 ]
Koren, Omry [3 ]
Ben-Hamo, Rotem [1 ]
Lerer-Goldshtein, Tal [1 ]
Rahimi, Roni [1 ]
Ben Horin, Shomron [4 ]
Nyska, Abraham [5 ]
Shpungin, Sally [1 ]
Nir, Uri [1 ,2 ]
机构
[1] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-5290002 Ramat Gan, Israel
[2] Bar Ilan Univ, Quaresa Inst Canc Res, IL-5290002 Ramat Gan, Israel
[3] Bar Ilan Univ, Fac Med, IL-1311502 Safed, Israel
[4] Chaim Sheba Med Ctr, Dept Gastroenterol, IL-52621 Tel Hashomer, Israel
[5] Tel Aviv Univ, Sackler Sch Med, IL-36576 Tel Aviv, Israel
关键词
co-housing; inflammatory bowel disease; mucus granule; ENTERIC PATHOGENS; EPITHELIAL-CELLS; GUT MICROBIOTA; MUC2; MUCIN; COLONIZATION; TMF/ARA160; DYSBIOSIS; EXERTS; DOMAIN; MODEL;
D O I
10.1073/pnas.1319114111
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:4964 / 4969
页数:6
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