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.

The saying "pastry chef to your cakes" is derisory for some professional careers. For example Elyar Fox , journalists are used to sharing jobs with people who have never studied the degree. In the world of fashion, this reality is not so far away. The Capsuled collections that actresses and soccer players develop for certain brands, as well as Vents journal announcements like the one about singer Rihanna as the creative director of a Puma line, made me wonder. What does it take to become a creative director of a fashion brand? Today we outline it For example conews feed

Introduction

Fasting can prolong survival and reduce disease burden in rodent models, and possibly in humans1. In contrast, today’s Western diet promotes cardiometabolic disease (CMD)2. How diet affects the gut microbiota, immune system and subsequently host (patho)physiology is not fully understood, and information is lacking on how periodic fasting affects the gut microbiome in patients with metabolic syndrome (MetS). To reduce CMD risk, exercise and a healthy diet are often prescribed. Shifting from a “Western diet” to a healthier “Mediterranean-like” DASH diet3 to achieve optimal nutrition and negative energy balance is recommended, although compliance is a major hurdle. Our study is the first of its kind to investigate the effects of a lifestyle modification in combination with fasting therapy in patients with MetS using a multi-omics approach by combining gut microbiome analysis and deep immunophenotyping. The “Western diet” is known to induce metabolic inflammation, accelerating CMD4. The gut microbiota is a delicate ecosystem that plays a pivotal role in health and disease. Dysbiosis has been observed as a characteristic of several inflammatory, cardiovascular, and metabolic disorders (e.g. obesity)5, including hypertension6,7. The “healthy” gut microbiome is relatively stable, although various factors such as antibiotics, intestinal infections, and profound dietary or lifestyle changes, such as moving on or off a “Western diet”, can induce transient or persistent changes to this ecosystem. Traditionally, fasting plays an important role in different cultural and religious practices. Dramatic caloric restriction not only affects host health and physiology, but also has an impact on the microbiome8,9,10. Here, we studied the role of fasting in cardiovascular risk patients with MetS (Table 1). Five days of fasting followed by 3 months of a modified DASH diet induced distinct microbiome and immunome changes not seen under DASH alone, as well as a sustained SBP benefit even 3 months post-intervention. Applying machine-learning algorithms, we were able to make effective predictions regarding which patients would respond positively to treatment via BP reduction from either baseline immunome or 16S microbiome data. The microbial signature for BP responsiveness generalizes to a recently published cohort investigating the impact of fasting in 15 healthy male volunteers, as do many of the microbiome changes upon fasting. These data highlight fasting followed by a shift to a health-promoting diet as a promising non-pharmacological intervention for patients with hypertensive MetS, with possible implications for a wider spectrum of health states.