Abstract
Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4+ effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8+ effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia, and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.
Highlights
Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet
As we have previously reported a major influence of common metabolic syndrome (MetS) drugs on the microbiota[11], we accounted for any changes in medication regime or dosage in our statistical tests, alongside controlling for important demographic features such as age and sex
An opposing pattern was shown by a poorly characterized Lachnospira sp., which had a higher abundance in responders at baseline (Fig. 8a). These findings indicate that baseline state of the gut microbiome in these MetS patients predicts individual degree of success of the fasting+Dietary Approaches to Stop Hypertension (DASH) intervention
Summary
Fasting affects the gut microbiome and immunome. As we have previously reported a major influence of common MetS drugs on the microbiota[11], we accounted for any changes in medication regime or dosage in our statistical tests, alongside controlling for important demographic features such as age and sex. There were substantial and significant (PERMANOVA P = 0.001) differences in microbial composition within individuals during fasting, reflecting a characteristic intervention-induced shift, which later partially reverted following a 3-month refeeding period on a DASH diet (Fig. 1d, Supplementary Data 1 and Fig. 1a). This was echoed by analogous significant (PERMANOVA P = 0.001) changes in host immune cell composition during the intervention, revealing a fasting-specific signature, which likewise largely reversed during refeeding (Fig. 1e, Supplementary Data 1). Fasting increased the abundance of monocytes (CD14 +CD11c+CD19−CD3−) and TCRγ/δ+ T cells These changes were reversed upon refeeding (Fig. 1h, Supplementary Data 1).
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