16 DNA sequencing. Rat adeno-associated virus

Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. Dysbiosis of the gut microbiome has been identified as one of the key environmental factors contributing to NAFLD. As an essential nutrient, vitamin D (VD) plays an important role in regulating gut microbiota, and its receptor [vitamin D receptor, (VDR)] is highly expressed in the gastrointestinal tract. Herein, we investigated the beneficial effects of VD on NAFLD by regulating the gut microbiota and metabolism. We discovered that the VD alleviates the high- fat diet (HFD)-induced lipid accumulation in the liver and decreases the levels of amlodipine besylate (ALT) and amlodipine aspartate (AST). VD supplement decreased the ratio of phylum Firmicutes/Bacteroidetes (F/B) but increased alpha diversity. In addition, the VD treatment improved the HFD-induced gut microbiota by increasing the Prevotella and Porphyromonadaceae and decreasing Mucispirillum, Acetatifactor, Desulfovibrio, and Oscillospira abundance. Furthermore, the capability of tyrosine metabolism, tryptophan metabolism, arginine biosynthesis, and sphingolipid metabolism was enhanced after VD treatment. Consistently, Prevotella positively correlated with tryptophan metabolism and sphingolipid metabolism. Importantly, the Prevotella abundance was positively associated with serotonin, melatonin, tryptamine, L-arginine, and 3-dehydrosphinganine which synthesize from tryptophan, tyrosine, argininosuccinate, and serine, respectively. In summary, our results show that VD supplement could be a potential intervention used for NAFLD treatment by targeting the specific microbiota.

非酒精性脂肪性肝病（Non-alcoholic fatty liver disease, NAFLD）是一类严重的公共卫生问题。肠道菌群失调已被证实是诱发NAFLD的关键环境因素之一。作为人体必需营养素，维生素D（vitamin D, VD）在调控肠道菌群方面发挥着重要作用，其受体维生素D受体（vitamin D receptor, VDR）在胃肠道中呈高表达。本研究通过调控肠道菌群与代谢，探究了VD对NAFLD的改善作用。研究发现，VD可缓解高脂饮食（high-fat diet, HFD）诱导的肝脏脂质堆积，并降低丙氨酸氨基转移酶（ALT）与天门冬氨酸氨基转移酶（AST）水平。VD补充可降低厚壁菌门/拟杆菌门（F/B）的比值，同时提升菌群α多样性。此外，VD处理可改善高脂饮食诱导的肠道菌群紊乱：增加普雷沃菌属（Prevotella）与卟啉单胞菌科（Porphyromonadaceae）的丰度，同时降低黏液螺菌属（Mucispirillum）、产乙酸杆菌属（Acetatifactor）、脱硫弧菌属（Desulfovibrio）以及颤螺菌属（Oscillospira）的丰度。进一步研究显示，VD处理可增强酪氨酸代谢、色氨酸代谢、精氨酸生物合成以及鞘脂代谢通路的活性。一致性分析表明，普雷沃菌属丰度与色氨酸代谢、鞘脂代谢呈正相关。尤为重要的是，普雷沃菌属丰度与5-羟色胺、褪黑素、色胺、L-精氨酸以及3-脱氢鞘氨醇呈正相关，上述物质分别由色氨酸、酪氨酸、精氨酸琥珀酸与丝氨酸合成。综上，本研究结果表明，VD补充或可通过靶向特定肠道菌群，成为NAFLD治疗的潜在干预手段。