Department for Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt-Goethe University, 60528 Frankfurt, Germany.
Department of Psychiatry and Neurosciences, UPC KU Leuven, Campus Gasthuisberg, KU Leuven, 3000 Leuven, Belgium.
Int J Mol Sci. 2022 Jul 27;23(15):8272. doi: 10.3390/ijms23158272.
The gut microbiota encodes a broad range of enzymes capable of synthetizing various metabolites, some of which are still uncharacterized. One well-known class of microbiota-derived metabolites are the short-chain fatty acids (SCFAs) such as acetate, propionate, butyrate and valerate. SCFAs have long been considered a mere waste product of bacterial metabolism. Novel results have challenged this long-held dogma, revealing a central role for microbe-derived SCFAs in gut microbiota-host interaction. SCFAs are bacterial signaling molecules that act directly on host T lymphocytes by reprogramming their metabolic activity and epigenetic status. They have an essential biological role in promoting differentiation of (intestinal) regulatory T cells and in production of the anti-inflammatory cytokine interleukin-10 (IL-10). These small molecules can also reach the circulation and modulate immune cell function in remote tissues. In experimental models of autoimmune and inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis or diabetes, a strong therapeutic potential of SCFAs through the modulation of effector T cell function was observed. In this review, we discuss current research activities toward understanding a relevance of microbial SCFA for treating autoimmune and inflammatory pathologies from in vitro to human studies.
肠道微生物群编码了广泛的酶，能够合成各种代谢物，其中一些代谢物仍未被描述。一类众所周知的微生物衍生代谢物是短链脂肪酸（SCFAs），如乙酸盐、丙酸盐、丁酸盐和戊酸盐。长期以来，SCFAs 一直被认为是细菌代谢的一种废物产物。新的研究结果挑战了这一长期以来的观点，揭示了微生物衍生的 SCFAs 在肠道微生物群与宿主相互作用中的核心作用。SCFAs 是细菌信号分子，通过重编程宿主 T 淋巴细胞的代谢活性和表观遗传状态，直接作用于宿主 T 淋巴细胞。它们在促进（肠道）调节性 T 细胞分化和产生抗炎细胞因子白细胞介素-10（IL-10）方面具有重要的生物学作用。这些小分子也可以到达循环系统，并调节远处组织中免疫细胞的功能。在自身免疫和炎症性疾病的实验模型中，如炎症性肠病、多发性硬化症或糖尿病，通过调节效应 T 细胞功能，观察到 SCFAs 具有很强的治疗潜力。在这篇综述中，我们讨论了目前从体外到人类研究理解微生物 SCFA 治疗自身免疫和炎症性病理的相关研究活动。
