Anthocyanin-enriched purple potato flour modulates gut microbiota and short-chain fatty acids to prevent hypertension: insights from preclinical models and mendelian randomization analysis

Hypertension remains a global health challenge with limited effective non-pharmacological interventions. This study investigated the antihypertensive effects of a potato-based functional diet using purple potato (PP) flour enriched with anthocyanins and potassium in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Over a 9-week dietary intervention, SHR and WKY rats were fed PP or yellow potato (YP) flour supplemented diets for preventive intervention. Blood pressure, serum biomarkers (angiotensin II, endothelin-1, nitric oxide), gut microbiota composition (16S rRNA sequencing), and cecal metabolites (untargeted metabolomics) were analyzed. Molecular docking assessed interactions between purple potato anthocyanins and hypertension-related proteins (endothelin-1, angiotensin II), while Mendelian randomization (MR) analysis evaluated genetic causality between potato intake and hypertension. Compared to YP, PP reduced both systolic blood pressure (SBP) by more than 18.23% in WKY rats but did not significantly affect SBP in SHR rats. PP also lowered serum angiotensin II by 33.08% in SHR rats and increased microbial diversity with elevated <i>Bacteroidota</i> abundance and reduced <i>Firmicutes</i>/<i>Bacteroidetes</i> ratio. Metabolomics analysis identified enriched pathways in bile acid metabolism and fatty acid biosynthesis, correlating with increased short-chain fatty acid (SCFA)-producing bacteria (<i>e.g.</i>, <i>Ruminococcus</i>, <i>Oscillibacter</i>). The metabolomics and gut microbiota correlation analysis indicated important interactions between metabolites and gut microbiota. Potato anthocyanins demonstrated strong binding affinity to endothelin-1/angiotensin II, suggesting direct bioactive potential. MR analysis revealed no causal link between potato intake and hypertension, highlighting the safety of nutrition intervention with potato for hypertension. The findings from this study underscore purple potato as a promising dietary strategy to modulate gut microbiota, enhance SCFA production, and prevent hypertension, emphasizing the role of whole-food interventions in cardiovascular health. Clinical translation, supported by estimated human-equivalent doses (75-150 g dry potato rice noodles per day), warrants further investigation.