Antibiotic-Induced Gut Microbiota Dysbiosis Modulates Host Transcriptome and m 6 A Epitranscriptome via Bile Acid Metabolism

• Published in: Advanced science 2024-07, Vol.11 (28), p.e2307981
• Main Authors: Yang, Meng, Zheng, Xiaoqi, Fan, Jiajun, Cheng, Wei, Yan, Tong-Meng, Lai, Yushan, Zhang, Nianping, Lu, Yi, Qi, Jiali, Huo, Zhengyi, Xu, Zihe, Huang, Jia, Jiao, Yuting, Liu, Biaodi, Pang, Rui, Zhong, Xiang, Huang, Shi, Luo, Guan-Zheng, Lee, Gina, Jobin, Christian, Eren, A Murat, Chang, Eugene B, Wei, Hong, Pan, Tao, Wang, Xiaoyun
• Format: Article
• Language: English
• Subjects: Adenosine - analogs & derivatives; Adenosine - metabolism; Animals; Anti-Bacterial Agents - pharmacology; Bile Acids and Salts - metabolism; Disease Models, Animal; Dysbiosis - genetics; Dysbiosis - metabolism; Dysbiosis - microbiology; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - genetics; Male; Mice; Mice, Inbred C57BL; Transcriptome - genetics
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202307981

Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N -methyladenosine (m A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m A epitranscriptome in multiple tissues. Mechanistically, the expression of m A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.