Dominant Bacterial Phyla from the Human Gut Show Widespread Ability To Transform and Conjugate Bile Acids
Dominant Bacterial Phyla from the Human Gut Show Widespread Ability To Transform and Conjugate Bile Acids
复制标题
DOI：
10.1128/msystems.00805-21
复制
发表时间：
2021-08-01
期刊：
影响因子：
6.4
通讯作者：
Amador-Noguez, D.
中科院分区：
文献类型：
--
作者：
Lucas, L. N.;Barrett, K.;Amador-Noguez, D.
肠道细菌通过对宿主合成的初级胆汁酸进行化学修饰来影响人体生理。这些修饰的胆汁酸被称为次级胆汁酸，可以作为信号分子调节宿主的脂肪、葡萄糖和能量代谢，并通过选择性的抗菌特性影响肠道微生物区系的组成。然而，关于单个肠道微生物的胆汁酸转化能力的知识仍然有限。为了帮助解决这一知识缺口，我们筛选了72株细菌分离物，跨越人类肠道中常见的七个主要门，以了解它们对未结合胆汁酸的化学修饰能力。我们发现，代表41个物种的43个分离株能够在体外对人类最丰富的三种未结合胆汁酸中的一种或多种进行修饰：胆酸、鹅去氧胆酸和脱氧胆酸。在这些物种中，有32种以前没有被描述为胆汁酸转换器。检测到的最常见的胆汁酸转化是类固醇核心上3a-、7a-或12a-羟基的氧化，这是一个由羟基类固醇脱氢酶催化的反应。此外，我们发现7a-脱羟基活性分布在不同的细菌属中，我们还观察到了其他几种复杂的胆汁酸转化。最后，我们的筛查揭示了初级和次级胆汁酸与甘氨酸和其他15种氨基酸的广泛细菌结合，导致发现了44种新的微生物结合胆汁酸。重要的是，我们目前关于微生物胆汁酸转化的知识主要来自对相对少数物种的生化研究或依赖于已知胆汁酸转化酶序列同源性的生物信息学预测。因此，关于胆汁酸转化的多样性及其在肠道微生物物种中的表现，仍有许多需要了解。通过对人类肠道中常见的细菌种类进行系统调查，这项研究有助于更好地定义影响胆酸池组成的肠道细菌，这在代谢紊乱和消化道癌症的背景下具有意义。我们的结果极大地扩展了已知的执行不同类型胆汁酸转化的细菌种类。这些知识对于评估微生物群、胆酸池组成和人类健康之间的因果关系至关重要。
Gut bacteria influence human physiology by chemically modifying hostsynthesized primary bile acids. These modified bile acids, known as secondary bile acids, can act as signaling molecules that modulate host lipid, glucose, and energy metabolism and affect gut microbiota composition via selective antimicrobial properties. However, knowledge regarding the bile acid-transforming capabilities of individual gut microbes remains limited. To help address this knowledge gap, we screened 72 bacterial isolates, spanning seven major phyla commonly found in the human gut, for their ability to chemically modify unconjugated bile acids. We found that 43 isolates, representing 41 species, were capable of in vitro modification of one or more of the three most abundant unconjugated bile acids in humans: cholic acid, chenodeoxycholic acid, and deoxycholic acid. Of these, 32 species have not been previously described as bile acid transformers. The most prevalent bile acid transformations detected were oxidation of 3a-, 7a-, or 12a- hydroxyl groups on the steroid core, a reaction catalyzed by hydroxysteroid dehydrogenases. In addition, we found 7a- dehydroxylation activity to be distributed across various bacterial genera, and we observed several other complex bile acid transformations. Finally, our screen revealed widespread bacterial conjugation of primary and secondary bile acids to glycine, a process that was thought to only occur in the liver, and to 15 other amino acids, resulting in the discovery of 44 novel microbially conjugated bile acids.IMPORTANCE Our current knowledge regarding microbial bile acid transformations comes primarily from biochemical studies on a relatively small number of species or from bioinformatic predictions that rely on homology to known bile acid-transforming enzyme sequences. Therefore, much remains to be learned regarding the variety of bile acid transformations and their representation across gut microbial species. By carrying out a systematic investigation of bacterial species commonly found in the human intestinal tract, this study helps better define the gut bacteria that impact composition of the bile acid pool, which has implications in the context of metabolic disorders and cancers of the digestive tract. Our results greatly expand upon the list of bacterial species known to perform different types of bile acid transformations. This knowledge will be vital for assessing the causal connections between the microbiome, bile acid pool composition, and human health.