Gut Microbial Metabolites Fuel Host Antibody Responses.
Gut Microbial Metabolites Fuel Host Antibody Responses.
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DOI：
10.1016/j.chom.2016.07.001
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发表时间：
2016-08-10
影响因子：
30.3
通讯作者：
Kim CH
中科院分区：
文献类型：
--
作者：
Kim M;Qie Y;Park J;Kim CH
抗体生产是一个代谢要求较高的过程，受肠道微生物群的调节，但支持 B 细胞反应的微生物产物仍未完全确定。我们报告说，肠道微生物群产生的短链脂肪酸（SCFA）作为膳食纤维的发酵产物，支持宿主抗体反应。在 B 细胞中，SCFA 会增加乙酰辅酶 A 并调节代谢传感器，以增加氧化磷酸化、糖酵解和脂肪酸合成，从而产生能量和支持抗体产生的构建模块。与此同时，SCFA 控制基因表达以表达血浆 B 细胞分化所需的分子。由于膳食纤维消耗减少或微生物不足而导致 SCFA 产量低的小鼠体内平衡和病原体特异性抗体反应有缺陷，导致病原体易感性更高。然而，SCFA 或膳食纤维的摄入可以恢复这种免疫缺陷。 SCFA 的这种 B 细胞辅助功能在从肠道到全身组织的整个过程中都可以检测到，并且在小鼠和人类 B 细胞中是保守的，凸显了其重要性。
Antibody production is a metabolically demanding process that is regulated by gut microbiota, but the microbial products supporting B cell responses remain incompletely identified. We report that short-chain fatty acids (SCFAs), produced by gut microbiota as fermentation products of dietary fiber, support host antibody responses. In B cells, SCFAs increase acetyl-CoA and regulate metabolic sensors to increase oxidative phosphorylation, glycolysis and fatty acid synthesis, which produce energy and building blocks supporting antibody production. In parallel, SCFAs control gene expression to express molecules necessary for plasma B cell differentiation. Mice with low SCFA production due to reduced dietary fiber consumption or microbial insufficiency are defective in homeostatic and pathogen-specific antibody responses, resulting in greater pathogen susceptibility. However, SCFA or dietary fiber intake restores this immune deficiency. This B cell-helping function of SCFAs is detected from the intestines to systemic tissues and conserved among mouse and human B cells, highlighting its importance.