Université de Rouen Normandie, INSERM UMR 1073, Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau, Rouen, France.
Université de Rouen Normandie, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
Gut Microbes. 2022 Jan-Dec;14(1):2108280. doi: 10.1080/19490976.2022.2108280.
The gut microbiota produces a wide variety of metabolites, which interact with intestinal cells and contribute to host physiology. The effect of gut commensal bacteria on host protein SUMOylation, an essential ubiquitin-like modification involved in various intestinal functions, remains, however, unknown. Here, we show that short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) produced by the gut microbiota increase protein SUMOylation in intestinal cells in a pH-dependent manner. We demonstrate that these metabolites inactivate intestinal deSUMOylases and promote the hyperSUMOylation of nuclear matrix-associated proteins. We further show that BCFAs inhibit the NF-κB pathway, decrease pro-inflammatory cytokine expression, and promote intestinal epithelial integrity. Together, our results reveal that fatty acids produced by gut commensal bacteria regulate intestinal physiology by modulating SUMOylation and illustrate a new mechanism of dampening of host inflammatory responses triggered by the gut microbiota.
肠道微生物群产生多种代谢物，这些代谢物与肠道细胞相互作用，有助于宿主生理机能。然而，肠道共生菌对宿主蛋白 SUMOylation 的影响，即一种参与各种肠道功能的必需泛素样修饰，仍然未知。在这里，我们表明肠道微生物群产生的短链脂肪酸 (SCFAs) 和支链脂肪酸 (BCFAs) 以 pH 依赖的方式增加肠道细胞中的蛋白质 SUMOylation。我们证明这些代谢物可使肠道去 SUMO 酶失活，并促进核基质相关蛋白的过度 SUMOylation。我们进一步表明，BCFAs 可抑制 NF-κB 通路，减少促炎细胞因子的表达，促进肠道上皮完整性。总之，我们的研究结果表明，肠道共生菌产生的脂肪酸通过调节 SUMOylation 来调节肠道生理机能，并阐明了肠道微生物群触发的宿主炎症反应的抑制的新机制。
