Journal Article

Intestinal epithelial Tet2 deficiency reprograms the gut microbiota through bile acid metabolic alterations

Huo, Fengjiao, Lv, Shuyao, Wang, Nan, Zhang, Shuaishuai, Mi, Taotao, Liu, Qing, Liu, Hailiang

2026

Overview

While the gut microbiota is known to influence host physiology, the molecular mechanisms by which the host epigenetically regulates microbial composition remain largely unexplored. Our work reveals that the epigenetic enzyme Tet2 in intestinal epithelial cells acts as a master regulator of gut microbial ecology by modulating bile acid metabolism. The discovery that Tet2 deletion drives hyocholic acid (HCA) accumulation—which exerts age-dependent effects on Lactobacillus and Akkermansia —provides a novel principle for understanding host–microbe interactions across the lifespan. By linking epithelial DNA demethylation to bile acid transport and microbial phenotype, we establish a previously unrecognized Tet2-ASBT-HCA pathway that expands the conceptual framework for microbiota research. These insights open new avenues for therapeutic interventions aimed at reversing microbial dysbiosis through epigenetic or metabolic modulation.

• Publisher: American Society for Microbiology
• Subject: Animal Models of Host-Microbiome Interactions / Epigenomics / Functional Genomics / Gut Microbiota / Host-Associated Microbiota / Host-Microbial Interactions / Host-Microbiome Interactions / Mechanisms of Host-Microbiome Communication / Methylation / Microbial Ecology and Evolution / Microbial Epigenomics / Microbial Genomics / Microbial Metabolism / Microbial Physiology and Genetics / Microbiome and Barrier Function / Microbiome and Disease Susceptibility / Microbiome and Host Metabolism / Microbiome Research / Observation / Protein Modification