Proximal colon-derived O-glycosylated mucus encapsulates and modulates the microbiota

被引:197
作者
Bergstrom, Kirk [1 ,2 ]
Shan, Xindi [1 ]
Casero, David [3 ]
Batushansky, Albert [4 ]
Lagishetty, Venu [5 ]
Jacobs, Jonathan P. [6 ]
Hoover, Christopher [1 ]
Kondo, Yuji [1 ]
Shao, Bojing [1 ]
Gao, Liang [1 ]
Zandberg, Wesley [7 ]
Noyovitz, Benjamin [7 ]
McDaniel, J. Michael [1 ]
Gibson, Deanna L. [2 ]
Pakpour, Sepideh [8 ]
Kazemian, Negin [8 ]
McGee, Samuel [1 ]
Houchen, Courtney W. [9 ]
Rao, Chinthalapally V. [9 ]
Griffin, Timothy M. [4 ,10 ]
Sonnenburg, Justin L. [11 ]
McEver, Rodger P. [1 ,10 ]
Braun, Jonathan [3 ]
Xia, Lijun [1 ,10 ]
机构
[1] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA
[2] Univ British Columbia, Dept Biol, Okanagan Campus, Kelowna, BC V1V 1V7, Canada
[3] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Inst, Los Angeles, CA 90048 USA
[4] Oklahoma Med Res Fdn, Aging & Metab Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Vatche & Tamar Manoukian Div Digest Dis, Los Angeles, CA 90095 USA
[6] VA Greater Angeles Healthcare Syst, Div Gastroenterol Hepatol & Parenteral Nutr, Los Angeles, CA 90025 USA
[7] Univ British Columbia, Dept Chem, Okanagan Campus, Kelowna, BC V1V 1V7, Canada
[8] Univ British Columbia, Sch Engn, Okanagan Campus, Kelowna, BC V1V 1V7, Canada
[9] Univ Oklahoma, Hlth Sci Ctr, Dept Internal Med, Oklahoma City, OK 73104 USA
[10] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA
[11] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA
关键词
GUT; COLITIS; GLYCANS; HEALTH; INNER;
D O I
10.1126/science.aay7367
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
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon-derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. Our work shows how proximal colon control of mucin production is an important element in the regulation of host-microbiota symbiosis.
引用
收藏
页码:467 / 472
页数:6
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