Microbial metabolites, short-chain fatty acids, restrain tissue bacterial load, chronic inflammation, and associated cancer in the colon of mice.
Microbial metabolites, short-chain fatty acids, restrain tissue bacterial load, chronic inflammation, and associated cancer in the colon of mice.
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DOI：
10.1002/eji.201747122
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发表时间：
2018-07
影响因子：
5.4
通讯作者：
Kim CH
中科院分区：
文献类型：
--
作者：
Kim M;Friesen L;Park J;Kim HM;Kim CH
肠道免疫系统受微生物及其代谢物的调节。肠道微生物代谢产物在调节肠道炎症和肿瘤发生中的作用尚不完全清楚。我们系统地研究了短链脂肪酸(SCFA)及其受体(GPR43或GPR41)在调节组织细菌负荷、急性和慢性炎症反应以及肠癌发生中的作用。SCFA受体缺陷小鼠，尤其是GPR43缺陷小鼠，在启动适当的急性免疫反应以促进屏障免疫方面存在缺陷，并在上皮损伤后出现失控的慢性炎症反应。此外，GPR43基因缺陷小鼠的肠道癌变增加。膳食纤维和SCFA通过GPR43依赖和独立的方式抑制肠道炎症和癌症。GPR43的有益作用不是通过改变微生物区系实现的，而是通过宿主组织细胞和造血细胞实现的。我们发现，无法抑制共生细菌对结肠组织的入侵与GPR43缺陷小鼠肠道中Th17驱动的慢性炎症和癌变的增加有关。总之，我们的结果揭示了SCFA-GPR43轴在抑制细菌入侵以及与之相关的结肠慢性炎症和癌变方面的有益功能。
The intestinal immune system is regulated by microbes and their metabolites. The roles of gut microbial metabolites in regulating intestinal inflammation and tumorigenesis are incompletely understood. We systematically studied the roles of short-chain fatty acids (SCFAs) and their receptors (GPR43 or GPR41) in regulating tissue bacterial load, acute versus chronic inflammatory responses, and intestinal cancer development. SCFA receptor-, particularly GPR43-, deficient mice were defective in mounting appropriate acute immune responses to promote barrier immunity, and developed uncontrolled chronic inflammatory responses following epithelial damage. Further, intestinal carcinogenesis was increased in GPR43-deficient mice. Dietary fiber and SCFA administration suppressed intestinal inflammation and cancer in both GPR43-dependent and independent manners. The beneficial effect of GPR43 was not mediated by altered microbiota but by host tissue cells and hematopoietic cells to a lesser degree. We found that inability to suppress commensal bacterial invasion into the colonic tissue is associated with the increased chronic Th17-driven inflammation and carcinogenesis in the intestine of GPR43-deficient mice. In sum, our results reveal the beneficial function of the SCFA-GPR43 axis in suppressing bacterial invasion and associated chronic inflammation and carcinogenesis in the colon.
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影响因子：
6
作者：
Kim CH;Park J;Kim M
通讯作者：
Kim M
影响因子：
29.4
作者：
Kang SG;Wang C;Matsumoto S;Kim CH
通讯作者：
Kim CH
影响因子：
10.5
作者：
Brennan CA;Garrett WS
通讯作者：
Garrett WS
影响因子：
30.3
作者：
Kelly CJ;Zheng L;Campbell EL;Saeedi B;Scholz CC;Bayless AJ;Wilson KE;Glover LE;Kominsky DJ;Magnuson A;Weir TL;Ehrentraut SF;Pickel C;Kuhn KA;Lanis JM;Nguyen V;Taylor CT;Colgan SP
通讯作者：
Colgan SP
肠道微生物群形成短链脂肪酸及其对人代谢的影响。
影响因子：
12.2
作者：
Morrison DJ;Preston T
通讯作者：
Preston T