Tuberculosis Research Program at the Centenary Institute, The University of Sydney , Camperdown, Australia.
Department of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine , Durham, NC, USA.
Gut Microbes. 2020 Nov 9;12(1):1-11. doi: 10.1080/19490976.2020.1824563.
Short-chain fatty acids (SCFAs) are produced by microbial fermentation of dietary fiber in the gut. Butyrate is a particularly important SCFA with anti-inflammatory properties and is generally present at lower levels in inflammatory diseases associated with gut microbiota dysbiosis in mammals. We aimed to determine if SCFAs are produced by the zebrafish microbiome and if SCFAs exert conserved effects on zebrafish immunity as an example of the non-mammalian vertebrate immune system. We demonstrate that bacterial communities from adult zebrafish intestines synthesize all three main SCFA , although SCFA were below our detectable limits in zebrafish intestines . Immersion in butyrate, but not acetate or propionate, reduced the recruitment of neutrophils and M1-type pro-inflammatory macrophages to wounds. We found conservation of butyrate sensing by neutrophils via orthologs of the () gene. Neutrophils from Hcar1-depleted embryos were no longer responsive to the anti-inflammatory effects of butyrate, while macrophage sensitivity to butyrate was independent of Hcar1. Our data demonstrate conservation of anti-inflammatory butyrate effects and identify the presence of a conserved molecular receptor in fish.
短链脂肪酸(SCFAs)是肠道中膳食纤维被微生物发酵产生的。丁酸盐是一种特别重要的具有抗炎特性的 SCFA,在与哺乳动物肠道微生物失调相关的炎症性疾病中,其含量通常较低。我们旨在确定 SCFAs 是否由斑马鱼微生物组产生,以及 SCFAs 是否对斑马鱼免疫产生保守作用,以此作为非哺乳动物脊椎动物免疫系统的一个例子。我们证明,来自成年斑马鱼肠道的细菌群落可以合成所有三种主要的 SCFA,但 SCFA 在斑马鱼肠道中的含量低于我们的检测限。丁酸浸泡,而不是乙酸或丙酸浸泡,可减少中性粒细胞和 M1 型促炎巨噬细胞向伤口的募集。我们发现,通过 ()基因的同源物,中性粒细胞对丁酸盐的感应具有保守性。来自 Hcar1 耗尽胚胎的中性粒细胞对丁酸盐的抗炎作用不再敏感,而巨噬细胞对丁酸盐的敏感性不依赖于 Hcar1。我们的数据表明,抗炎性丁酸盐作用具有保守性,并确定了鱼类中存在保守的分子受体。