Fasting alters the gut microbiome with sustained blood pressure and body weight reduction in metabolic syndrome patients

Abstract Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. We show that in hypertensive metabolic syndrome (MetS) patients (n=35), a 5-day fast followed by a modified DASH diet (Dietary Approach to Stop Hypertension) reduced systolic blood pressure (SBP), antihypertensive medication need, and body-mass index (BMI) at three months post intervention compared to a modified DASH diet alone (n=36). Fasting altered the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses revealed a positive correlation of circulating mucosa-associated invariant T (MAIT) cells, non-classical monocytes and CD4+ effector T cells with SBP. Furthermore, regulatory T cells (Tregs) positively correlated with BMI and weight. Machine learning could predict sustained SBP-responsiveness within the fasting group from baseline immunome data, identifying CD8+ effector T cells, Th17 cells and Tregs as important contributors to the model. The high-resolution multi-omics data highlights fasting as a promising non-pharmacological intervention in MetS.