Genetical TRPV4 deletion-associated gut microbiota alleviates cardiac dysfunction in mice with diabetic...

Diabetic cardiomyopathy (DCM) is a serious complication associated with diabetes that characterized by the cardiac dysfunction and myocardial fibrosis. Recent studies emphasize the significance of the gut-heart axis in the development of DCM. This current study investigates the effect of systematic-genetical TRPV4 knockout on DCM progression and explores the underlying mechanisms involving gut microbiota modulation and intestinal barrier integrity. The removal of TRPV4 in mice with DCM markedly enhances cardiac performance, decreases myocardial fibrosis, and modifies the composition of gut microbiota, resulting in a significant rise in Bacteroides acidifaciens (BA). TRPV4 deletion also upregulates tight junction proteins (Zonula occludens-1 (ZO-1), Occludin, and Claudin-1) and reduces serum lipopolysaccharide levels. Furthermore, fecal microbiota transplantation from the DCM donors with TRPV4 knockout to the DCM receptors replicates these cardioprotective effects in mice, and administration of BA improves cardiac function and relieves the fibrosis. Our study suggests that the cardioprotective effects of the genetic deletion of TRPV4 are related to changes in the gut microbiome, highlighting the importance of the connection between TRPV4, the gut, and the heart in the disease mechanism and potential therapeutic strategies for DCM.