NTCP蛋白是人类乙肝/丁肝病毒受体，也是抗乙肝/丁肝病毒药物的重要作用靶点。但长期服用NTCP阻断药物的副作用难以通过临床试验和动物实验进行评估。在前期研究中，我们收集到8例罕见的NTCP编码基因p.Ser267Phe纯合突变个体，其NTCP失去大部分功能，因此是研究长期阻断NTCP的安全性的理想模型。我们发现所有的个体维生素D水平降低。在预实验的宏基因组分析中，我们发现这些个体肠道菌属发生改变，有可能与胆汁酸及维生素D代谢相关。本研究计划对NTCP纯合性突变个体进行血液及肠道总胆汁酸和胆汁酸谱的检测，血液维生素D检测并进行个体肠道菌群研究，以揭示NTCP长期阻断后维生素D代谢机制，为理解与控制NTCP阻断药物长期使用的副作用提供理论依据。

NTCP is a receptor for human hepatitis B (HBV)/hepatitis D virus (HDV). However, it is difficult to evaluate the side effects of long-term NTCP blocking drugs in chronic hepatitis by clinical and animal experiments. The homozygosity of p.Ser267Phe of the gene SLC10A1. We previously had identified eight individuals with homozygousp.Ser267Phe mutation in SLC10A1, which code for NTCP, losses most functions of the wild-type gene. Therefore, individuals with homozygousp.Ser267Phe mutation in SLC10A1 provide the best model to study the possible side-effects of the long-term blockage of NTCP by anti-HBV/HDV drugs. The levels of vitamin D in all homozygous individuals was lower than normal range. In the pre-experimental metagenomic analysis, we found that several intestinal bacteria in these individuals altered. Therefore, we propose that in the case of NTCP blockade, lead to changes in the serum and intestinal bile acids, which may affecting the regulation of bile acids and vitamin D metabolism. The aim of this study is to quantify the total bile acid in serum and intestine of homozygote individuals and to study the gut microbiota and transcriptome of NTCP homozygote individuals, so as to reveal the regulation mechanism of gut microbiota participating in vitamin D metabolism after long-term NTCP blockade, and to provide theoretical basis for understanding and controlling the side effects of long-term NTCP blockade drugs.