Improving gut dysbiosis and impaired gut–brain axis has been a potent therapeutic strategy for treating myocardial infarction (MI). Geniposide (GEN), a traditional Chinese medicine extract, has demonstrated substantial cardioprotective properties post‐MI. Nevertheless, the effect of GEN on gut microbial, gut–brain communication, and its potential mechanism remains unclear. In this study, we initially found that GEN significantly alleviated MI‐induced cardiac dysfunction from echocardiographic data and decreased myocardial fibrosis, inflammation, apoptosis and hypertrophy post‐MI. Additionally, we investigated the effects of GEN on gut pathology, and observed that GEN led to a remarkable change in gut microbiota as evidenced by altering β‐diversity and short‐chain fatty acids (SCFAs) levels, and alleviated intestinal damage indicated by reduced inflammation and barrier permeability post‐MI. Finally, our investigation into brain pathology revealed that GEN induced a remarkable inhibition in PVN inflammation and sympathetic activity following MI. Collectively, these findings imply that the cardioprotective effects of GEN against MI were mediated possibly via an improvement in the impaired gut–brain axis. Mechanically, GEN‐induced increase of microbiota‐derived SCFAs might be the critical factor linking gut microbiota and reduced neuroinflammation with PVN, which leads to the suppression of sympathetic activation, therefore protecting the myocardium against MI‐induced damage.

Cardiovascular disease (CVD) and chronic kidney disease (CKD) are the leading causes of mortality and health burden worldwide

Objects: Taurine exhibits protective effects in the context of cardiovascular pathophysiology. A range of evidence suggests that hypertension activates inflammatory responses and oxidative stress in the paraventricular nucleus (PVN), elevating the arterial tone and sympathetic activity, while it induces gut–brain axis dysfunction in the context of hypertension. However, the mechanism underlying taurine’s anti-hypertensive effects via the gut–brain axis remains unclear. Method: Male spontaneously hypertensive rats (SHRs) were administered 3% taurine in their drinking water for eight weeks, with their arterial pressure measured weekly. Molecular techniques were employed to investigate taurine’s effects on the hypertensive gut and PVN. Additionally, 16S rRNA gene sequencing was used to analyze the gut microbiota composition, and untargeted metabolomics was applied to assess the fecal metabolites following taurine supplementation. Results: Taurine supplementation not only reduced the blood pressure, sympathetic activity, and inflammatory and oxidative stress in the PVN but also improved the cardiac pathology and microbiota composition while alleviating gut inflammation in hypertensive rats. The untargeted metabolite analysis indicated that the primary effect of the taurine intervention in SHRs was exerted on tryptophan metabolism. The levels of serum metabolites such as kynurenine, L-tryptophan, serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) were altered in hypertensive rats following taurine treatment. Conclusions: Taurine supplementation restored the microbiota balance, strengthened the mucosal barrier, reduced intestinal inflammation, and stimulated tryptophan metabolism. The metabolites derived from the gut microbiota likely crossed the brain barrier and reached the paraventricular nucleus, thereby reducing the inflammatory responses and oxidative stress in the PVN via gut–brain communication, leading to decreased sympathetic nerve activity and blood pressure in the studied hypertensive rats.