Department of Chemistry and The Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
Division of Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
Microbiome. 2023 Apr 27;11(1):91. doi: 10.1186/s40168-023-01540-y.
Lactic acid bacteria (LAB) produce various bioactive secondary metabolites (SMs), which endow LAB with a protective role for the host. However, the biosynthetic potentials of LAB-derived SMs remain elusive, particularly in their diversity, abundance, and distribution in the human microbiome. Thus, it is still unknown to what extent LAB-derived SMs are involved in microbiome homeostasis.
Here, we systematically investigate the biosynthetic potential of LAB from 31,977 LAB genomes, identifying 130,051 secondary metabolite biosynthetic gene clusters (BGCs) of 2,849 gene cluster families (GCFs). Most of these GCFs are species-specific or even strain-specific and uncharacterized yet. Analyzing 748 human-associated metagenomes, we gain an insight into the profile of LAB BGCs, which are highly diverse and niche-specific in the human microbiome. We discover that most LAB BGCs may encode bacteriocins with pervasive antagonistic activities predicted by machine learning models, potentially playing protective roles in the human microbiome. Class II bacteriocins, one of the most abundant and diverse LAB SMs, are particularly enriched and predominant in the vaginal microbiome. We utilized metagenomic and metatranscriptomic analyses to guide our discovery of functional class II bacteriocins. Our findings suggest that these antibacterial bacteriocins have the potential to regulate microbial communities in the vagina, thereby contributing to the maintenance of microbiome homeostasis.
Our study systematically investigates LAB biosynthetic potential and their profiles in the human microbiome, linking them to the antagonistic contributions to microbiome homeostasis via omics analysis. These discoveries of the diverse and prevalent antagonistic SMs are expected to stimulate the mechanism study of LAB's protective roles for the microbiome and host, highlighting the potential of LAB and their bacteriocins as therapeutic alternatives. Video Abstract.
乳酸菌（LAB）产生各种生物活性次级代谢产物（SMs），赋予 LAB 对宿主的保护作用。然而，LAB 衍生 SMs 的生物合成潜力仍然难以捉摸，尤其是在其多样性、丰度和在人类微生物组中的分布方面。因此，LAB 衍生 SMs 在多大程度上参与微生物组稳态仍然未知。
在这里，我们系统地研究了 31977 个 LAB 基因组中 LAB 的生物合成潜力，鉴定了 2849 个基因簇家族（GCF）中的 130051 个次级代谢产物生物合成基因簇（BGC）。这些 GCF 中的大多数是种特异性的，甚至是菌株特异性的，而且尚未被描述。通过分析 748 个人类相关宏基因组，我们深入了解了 LAB BGC 在人类微生物组中的多样性和生态位特异性。我们发现，大多数 LAB BGC 可能编码具有机器学习模型预测的普遍拮抗活性的细菌素，在人类微生物组中可能发挥保护作用。II 类细菌素是最丰富和最多样化的 LAB SM 之一，在阴道微生物组中特别丰富和占主导地位。我们利用宏基因组和宏转录组分析来指导我们发现功能 II 类细菌素。我们的研究结果表明，这些抗菌细菌素有可能调节阴道中的微生物群落，从而有助于维持微生物组稳态。
我们的研究系统地研究了 LAB 的生物合成潜力及其在人类微生物组中的分布情况，通过组学分析将其与对微生物组稳态的拮抗贡献联系起来。这些发现的多样化和普遍存在的拮抗 SMs 有望刺激对 LAB 对微生物组和宿主保护作用的机制研究，突出了 LAB 及其细菌素作为治疗替代品的潜力。
