MicroRNA‐29a Compromises Hepatic Adiposis and Gut Dysbiosis in High Fat Diet‐Fed Mice via Downregulating Inflammation

Scope miR‐29a expression patterns influence numerous physiological phenomena. Of note, upregulation of miR‐29a ameliorates high‐fat diet (HFD)‐induced liver dysfunctions in mice. However, the miR‐29a effect on gut microbiome composition and HFD‐induced gut microbiota changes during metabolic disturbances remains unclear. The study provides compelling evidence for the protective role of miR‐29a in gut barrier dysfunction and steatohepatitis. Methods and results miR‐29a overexpressed mice (miR‐29aTg) are bred to characterize intestinal, serum biochemical, and fecal microbiota profiling features compared to wild‐type mice (WT). Mice are fed an HFD for 8 months to induce steatohepatitis, and intestinal dysfunction is determined via histopathological analysis. miR‐29aTg has better lipid metabolism capability that decreases total cholesterol and triglyceride levels in serum than WT of the same age. The study further demonstrates that miR‐29aTg contributes to intestinal integrity by maintaining periodic acid Schiff positive cell numbers and diversity of fecal microorganisms. HFD‐induced bacterial community disturbance and steatohepatitis result in more severe WT than miR‐29aTg. Gut microorganism profiling reveals Lactobacillus, Ruminiclostridium_9, and Lachnoclostridium enrichment in miR‐29aTg and significantly decreases interleukin‐6 expression in the liver and intestinal tract. Conclusion This study provides new evidence that sheds light on the host genetic background of miR‐29a, which protects against steatohepatitis and other intestinal disorders. HFD feeding resulted in steatohepatitis, leaky gut, and dysbiosis, with more severe damage in WT than in miR‐29aTg. miR‐29a demonstrated to act as a master regulator influencing numerous physiological phenomena. Notably, miR‐29a accessibility ameliorates HFD‐induced metabolic dysregulation and inflammation. This study provides new evidence to shed light on the miR‐29a link between metabolic homeostasis and advanced intestinal microbiota diversity.