CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands.
CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands.
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作者：
宿主和肠道微生物区系之间复杂的相互作用控制着肠道的动态平衡，但仍然知之甚少。在这里，我们揭示了肠道微生物区系与caspase招募结构域家族成员9(CARD9)之间的关系，CARD9是炎症性肠病(IBD)的易感基因，在针对微生物的免疫反应中发挥作用。CARD9通过促进IL-22的产生促进结肠炎的恢复，而CARD9−/−小鼠更容易患结肠炎。在CARD9−/−小鼠中，微生物区系发生了变化，将微生物区系从CARD9−/−转移到野生型、无菌的接受者增加了他们对结肠炎的易感性。来自CARD9−/−小鼠的微生物区系不能将色氨酸代谢成作为芳烃受体配体的代谢物。在给小鼠接种三种能够代谢色氨酸的乳杆菌菌株或用AHR激动剂治疗后，肠道炎症可以减轻。在IBD患者的微生物区系中也观察到AHR配体的产生减少，特别是在那些与IBD相关的CARD9风险等位基因的患者中。我们的发现表明，宿主基因影响肠道微生物区系的组成和功能，改变微生物代谢物的产生和肠道炎症。
Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9−/− mice are more susceptible to colitis. The microbiota is altered in Card9−/− mice, and transfer of the microbiota from Card9−/− to wild-type, germ-free recipients increases their susceptibility to colitis. The microbiota from Card9−/− mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation.
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影响因子：
4.1
作者：
He, Guochun;Zhao, Bin;Denison, Michael S.
通讯作者：
Denison, Michael S.
影响因子：
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影响因子：
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通讯作者：
Colonna, Marco
DOI：
10.1126/science.1221789
发表时间：
2012-06-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iliev ID;Funari VA;Taylor KD;Nguyen Q;Reyes CN;Strom SP;Brown J;Becker CA;Fleshner PR;Dubinsky M;Rotter JI;Wang HL;McGovern DP;Brown GD;Underhill DM
通讯作者：
Underhill DM
DOI：
10.4049/jimmunol.182.2.1146
发表时间：
2009-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Goodridge HS;Shimada T;Wolf AJ;Hsu YM;Becker CA;Lin X;Underhill DM
通讯作者：
Underhill DM