Single‐microbe RNA sequencing uncovers unexplored specialized metabolic functions of keystone species in the human gut

作者：Yifei Shen, Wenxin Qu, Mengdi Song, Tianyu Zhang, Chang Liu, Xiaofeng Shi, Xinxin Xu, Jingjing Jiang, Liguo Ding, Fangyu Mo, Zheying Mao, Mingzhu Huang, Ziye Xu, Jiaye Chen, Enhui Shen, Jian Ruan, Jiong Liu, Michael P. Timko, Yu Chen, Longjiang Fan, Shufa Zheng, Yongcheng Wang · 发表于：iMeta · 年份：2025 · DOI：10.1002/imt2.70035 · 被引用次数：9 · 研究领域：Gut microbiota and health、RNA modifications and cancer、Helicobacter pylori-related gastroenterology studies

Abstract The human body is inhabited by trillions of microorganisms that play a crucial role in health and diseases. Our understanding of the species and functional composition of the human gut microbiome is rapidly expanding, but it is still mainly based on taxonomic profiles or gene abundance measurements. As such, little is known about the species–function heterogeneity and dynamic activities in human microecosystem niches. By applying a novel gut‐specific single‐microbe ribonucleic acid (RNA) sequencing and analytical framework on three healthy donors with distinct enterotypes, we created a comprehensive transcriptional landscape of the human gut microbiome and dissected functional specialization in 38,922 single microbes across 198 species. We investigated the functional redundancy and complementarity involved in short‐chain fatty acids related central carbon metabolism and studied the heterogeneity and covariation of single‐microbe metabolic capacity. Comparing the human gut microbiome at different times throughout the day, we were able to map diurnal dynamic activities of the gut microbiome and discovered its association with sub‐population functional heterogeneous. Remarkably, using single‐microbe RNA sequencing, we systematically dissected the metabolic function heterogeneity of Megamonas funiformis , a keystone species in Asian populations. Together with in vitro and in vivo experimental validations, we proved M. funiformis can effectively improve mineral absorption...