Yang Yuwei, Gao Wenxing, Zhu Ruixin, Tao Liwen, Chen Wanning, Zhu Xinyue, Shen Mengping, Xu Tingjun, Zhao Tingting, Zhang Xiaobai, Zhu Lixin, Jiao Na
Putuo People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
mSystems. 2025 Jan 21;10(1):e0081724. doi: 10.1128/msystems.00817-24. Epub 2024 Dec 17.
Microbial metabolism of bile acids (BAs) is crucial for maintaining homeostasis in vertebrate hosts and environments. Although certain organisms involved in bile acid metabolism have been identified, a global, comprehensive elucidation of the microbes, metabolic enzymes, and bile acid remains incomplete. To bridge this gap, we employed hidden Markov models to systematically search in a large-scale and high-quality search library comprising 28,813 RefSeq multi-kingdom microbial complete genomes, enabling us to construct a secondary bile acid production gene catalog. This catalog greatly expanded the distribution of secondary bile acid production genes across 11 phyla, encompassing bacteria, archaea, and fungi, and extended to 14 habitats spanning hosts and environmental contexts. Furthermore, we highlighted the associations between secondary bile acids (SBAs) and gastrointestinal and hepatic disorders, including inflammatory bowel disease (IBD), colorectal cancer (CRC), and nonalcoholic fatty liver disease (NAFLD), further elucidating disease-specific alterations in secondary bile acid production genes. Additionally, we proposed the pig as a particularly suitable animal model for investigating secondary bile acid production in humans, given its closely aligned secondary bile acid production gene composition. This gene catalog provides a comprehensive and reliable foundation for future studies on microbial bile acid metabolism, offering new insights into the microbial contributions to health and disease.
Bile acid metabolism is an important function in both host and environmental microorganisms. The existing functional annotations from single source pose limitations on cross-habitat analysis. Our construction of a systematic secondary bile acid production gene catalog encompassing numerous high-quality reference sequences propelled research on bile acid metabolism in the global microbiome, holding significance for the concept of One Health. We further highlighted the potential of the microbiota-secondary bile acid axis as a target for the treatment of hepatic and intestinal diseases, as well as the varying feasibility of using animal models for studying human bile acid metabolism. This gene catalog offers a solid groundwork for investigating microbial bile acid metabolism across different compartments, including humans, animals, plants, and environments, shedding light on the contributions of microorganisms to One Health.
胆汁酸（BAs）的微生物代谢对于维持脊椎动物宿主和环境中的稳态至关重要。尽管已经鉴定出一些参与胆汁酸代谢的生物体，但对微生物、代谢酶和胆汁酸的全面、系统的阐明仍不完整。为了弥补这一差距，我们采用隐马尔可夫模型在一个包含28,813个RefSeq多界微生物完整基因组的大规模、高质量搜索库中进行系统搜索，从而构建了一个次级胆汁酸产生基因目录。该目录极大地扩展了次级胆汁酸产生基因在11个门中的分布，包括细菌、古菌和真菌，并扩展到涵盖宿主和环境背景的14种栖息地。此外，我们强调了次级胆汁酸（SBAs）与胃肠道和肝脏疾病之间的关联，包括炎症性肠病（IBD）、结直肠癌（CRC）和非酒精性脂肪性肝病（NAFLD），进一步阐明了次级胆汁酸产生基因中特定疾病的改变。此外，鉴于猪的次级胆汁酸产生基因组成与人类密切相关，我们提出猪是研究人类次级胆汁酸产生的特别合适的动物模型。这个基因目录为未来微生物胆汁酸代谢研究提供了全面可靠的基础，为微生物对健康和疾病的贡献提供了新的见解。
胆汁酸代谢是宿主和环境微生物中的一项重要功能。来自单一来源的现有功能注释对跨栖息地分析存在局限性。我们构建的包含众多高质量参考序列的系统性次级胆汁酸产生基因目录推动了全球微生物组中胆汁酸代谢的研究，对“同一个健康”概念具有重要意义。我们进一步强调了微生物群 - 次级胆汁酸轴作为治疗肝脏和肠道疾病靶点的潜力，以及使用动物模型研究人类胆汁酸代谢的不同可行性。这个基因目录为研究包括人类、动物、植物和环境在内的不同区室中的微生物胆汁酸代谢提供了坚实基础，揭示了微生物对“同一个健康”的贡献。
