School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Microbiome. 2019 Jan 23;7(1):9. doi: 10.1186/s40168-019-0628-3.
Bile salt hydrolase plays an important role in bile acid-mediated signaling pathways, which regulate lipid absorption, glucose metabolism, and energy homeostasis. Several reports suggest that changes in the composition of bile acids are found in many diseases caused by dysbacteriosis.
Here, we present the taxonomic identification of bile salt hydrolase (BSH) in human microbiota and elucidate the abundance and activity differences of various bacterial BSH among 11 different populations from six continents. For the first time, we revealed that bile salt hydrolase protein sequences (BSHs) are distributed in 591 intestinal bacterial strains within 117 genera in human microbiota, and 27.52% of these bacterial strains containing BSH paralogs. Significant variations are observed in BSH distribution patterns among different populations. Based on phylogenetic analysis, we reclassified these BSHs into eight phylotypes and investigated the abundance patterns of these phylotypes among different populations. From the inspection of enzyme activity among different BSH phylotypes, BSH-T3 showed the highest enzyme activity and is only found in Lactobaclillus. The phylotypes of BSH-T5 and BSH-T6 mainly from Bacteroides with high percentage of paralogs exhibit different enzyme activity and deconjugation activity. Furthermore, we found that there were significant differences between healthy individuals and patients with atherosclerosis and diabetes in some phylotypes of BSHs though the correlations were pleiotropic.
This study revealed the taxonomic and abundance profiling of BSH in human gut microbiome and provided a phylogenetic-based system to assess BSHs activity by classifying the target sequence into specific phylotype. Furthermore, the present work disclosed the variation patterns of BSHs among different populations of geographical regions and health/disease cohorts, which is essential to understand the role of BSH in the development and progression of related diseases.
胆盐水解酶在胆汁酸介导的信号通路中发挥重要作用，该通路调节脂质吸收、葡萄糖代谢和能量稳态。有几项报告表明，许多由菌群失调引起的疾病中都发现了胆汁酸组成的变化。
在这里，我们对人类微生物群中的胆盐水解酶（BSH）进行了分类鉴定，并阐明了来自六大洲的 11 个人群中各种细菌 BSH 的丰度和活性差异。我们首次揭示了胆盐水解酶蛋白序列（BSHs）分布在人类微生物群 117 个属的 591 个肠道细菌菌株中，其中 27.52%的细菌菌株含有 BSH 旁系同源物。不同人群中 BSH 的分布模式存在显著差异。基于系统发育分析，我们将这些 BSH 重新分类为 8 个宗型，并研究了这些宗型在不同人群中的丰度模式。通过对不同 BSH 宗型的酶活性进行检查，BSH-T3 表现出最高的酶活性，仅存在于乳杆菌属中。BSH-T5 和 BSH-T6 的宗型主要来自拟杆菌属，其旁系同源物比例较高，表现出不同的酶活性和去结合活性。此外，我们发现，尽管相关性是多效的，但在某些 BSH 宗型中，健康个体与动脉粥样硬化和糖尿病患者之间存在显著差异。
本研究揭示了人类肠道微生物组中 BSH 的分类和丰度特征，并提供了一种基于系统发育的方法，通过将目标序列分类到特定的宗型来评估 BSH 的活性。此外，本工作揭示了不同地理区域和健康/疾病队列人群中 BSH 的变化模式，这对于理解 BSH 在相关疾病的发生和发展中的作用至关重要。
