Zhao Ni, Geng Peiling, Perez Alejandro Gaher, Maya Anakha Chandramana, Yadav Brijesh, Du Yuxuan, Ge Yong
Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health San Antonio, San Antonio, Texas, USA.
Department of Electrical and Computer Engineering, University of Texas at San Antonio, San Antonio, Texas, USA.
mSystems. 2025 Aug 19;10(8):e0079025. doi: 10.1128/msystems.00790-25. Epub 2025 Jul 9.
The gut is the most complex microbial ecosystem in the body that greatly influences human immune and metabolic health. However, the functional understanding of gut microbiome is hampered by our limited ability to obtain bacterial cultures for experimental validation, particularly low-abundant species that may carry specific functions but are often overlooked by population-based analyses. Here, we isolated and characterized a novel strain of (named Bp 531D) from human gut microbiota, representing the first butyrate-producing human isolate within a phylogenetic clade of complex. Comparative whole-genome analysis revealed a unique capability of Bp 531D for one-carbon metabolism and a high abundance of mobile genetic elements, including six prophages and plentiful transposons, reflecting its evolutionary flexibility. Oral administration of the bacterium profoundly altered gut microbiome composition in C57BL/6 mice, leading to controlled microbial oxidative signaling and calibrated carbohydrate metabolic function in the gut. RNA sequencing (RNA-seq) analysis demonstrated notable functional programming of colonic ECs, whereupon Bp 531D primarily restricted the biosynthesis of cholesterols and activated the pathway of antigen processing and presentation. Furthermore, the expression of MHC class II was correlatively heightened in colonic dendritic cells (DCs), and the frequencies of interleukin-10- (IL-10) and IL-22-producing T helper 17 (Th17) cells were significantly elevated in mice treated with Bp 531D compared to controls. Our findings uncover the crucial roles of in supporting intestinal homeostasis and provide a novel functional modulator to potentially optimize microbial strategies for improving intestinal health.IMPORTANCEReduced abundance of the genus has been associated with human intestinal disorders, including inflammatory bowel diseases. While supplementation of mitigates intestinal inflammation, it is unclear whether other species critically contribute to intestinal microbial and immune homeostasis. We identified a novel species within human gut microbiota and characterized its detailed intestinal functions using the C57BL/6 mouse model. Our findings may further highlight the genetic and functional diversities of the gut microbiome.
肠道是人体中最复杂的微生物生态系统，对人类免疫和代谢健康有重大影响。然而，由于我们获取细菌培养物用于实验验证的能力有限，尤其是对于那些可能具有特定功能但在基于群体的分析中经常被忽视的低丰度物种，阻碍了我们对肠道微生物群功能的理解。在此，我们从人类肠道微生物群中分离并鉴定了一种新菌株（命名为Bp 531D），它代表了在复杂系统发育分支中首个产生丁酸盐的人类分离株。比较全基因组分析揭示了Bp 531D在一碳代谢方面的独特能力以及大量的移动遗传元件，包括六个原噬菌体和丰富的转座子，反映了其进化灵活性。口服该细菌可显著改变C57BL/6小鼠的肠道微生物群组成，导致肠道内微生物氧化信号得到控制以及碳水化合物代谢功能得到校准。RNA测序（RNA-seq）分析表明结肠上皮细胞有显著的功能编程，在此过程中Bp 531D主要限制胆固醇的生物合成并激活抗原加工和呈递途径。此外，结肠树突状细胞（DCs）中MHC II类分子的表达相应升高，与对照组相比，用Bp 531D处理的小鼠中产生白细胞介素-10（IL-10）和IL-22的辅助性T细胞17（Th17）细胞的频率显著升高。我们的研究结果揭示了在维持肠道稳态中的关键作用，并提供了一种新的功能调节剂，有可能优化改善肠道健康的微生物策略。重要性 属丰度降低与包括炎症性肠病在内的人类肠道疾病有关。虽然补充可减轻肠道炎症，但尚不清楚其他物种是否对肠道微生物和免疫稳态有重要贡献。我们在人类肠道微生物群中鉴定出一个新物种，并使用C57BL/6小鼠模型对其详细的肠道功能进行了表征。我们的研究结果可能会进一步突出肠道微生物群的遗传和功能多样性。
