Lucas L N, Barrett K, Kerby R L, Zhang Q, Cattaneo L E, Stevenson D, Rey F E, Amador-Noguez D
Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, Wisconsin, USA.
mSystems. 2021 Aug 31:e0080521. doi: 10.1128/mSystems.00805-21.
Gut bacteria influence human physiology by chemically modifying host-synthesized 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 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 3α-, 7α-, or 12α-hydroxyl groups on the steroid core, a reaction catalyzed by hydroxysteroid dehydrogenases. In addition, we found 7α-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. 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.
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。这些经修饰的胆汁酸，即次级胆汁酸，可作为信号分子调节宿主的脂质、葡萄糖和能量代谢，并通过选择性抗菌特性影响肠道微生物群的组成。然而，关于个体肠道微生物转化胆汁酸能力的了解仍然有限。为了填补这一知识空白，我们筛选了72株细菌分离株，这些分离株来自人类肠道中常见的七个主要门，以检测它们对未结合胆汁酸进行化学修饰的能力。我们发现，43株分离株（代表41个物种）能够对人类三种最丰富的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。其中，32个物种此前未被描述为胆汁酸转化菌。检测到的最常见的胆汁酸转化是类固醇核心上3α-、7α-或12α-羟基的氧化，该反应由羟基类固醇脱氢酶催化。此外，我们发现7α-脱羟基活性分布于各种细菌属中，并且我们还观察到了其他几种复杂的胆汁酸转化。最后，我们的筛选揭示了初级和次级胆汁酸与甘氨酸以及其他15种氨基酸的广泛细菌共轭作用，从而发现了44种新型微生物共轭胆汁酸。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与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有待了解之处。通过对人类肠道中常见细菌物种进行系统研究，本研究有助于更好地确定影响胆汁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重要意义。我们的结果极大地扩充了已知能进行不同类型胆汁酸转化的细菌物种名单。这些知识对于评估微生物群、胆汁酸池组成和人类健康之间的因果关系至关重要。
