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May 2021

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Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients. nature communications 2021. DZHK authors: András Maifeld, Hendrik Bartolomaeus, Ulrike Löber, Ellen G. Avery, Lajos Markó, Nicola Wilck, Anja Mähler, Chia-Yu Chen, Ralf Dechend, Dominik N. Müller, Sofia K. Forslund

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Hypertension, as a component of the metabolic syndrome, is a risk factor for multiple further cardiovascular endpoints. Anecdotally, episodic fasting may improve components of the metabolic syndrome, and it is both seen in many traditional practices and likely to reflect living conditions throughout our evolutionary past, whereas it is absent from the "Western lifestyle". That also incorporates other dietary risk factors, many of which are reversed in the Dietary Approaches to Stop Hypertension (DASH) diet, one of few with substantial evidence backing it. However, efficacy of dietary interventions remains variable, and mechanisms underlying the anecdotal health benefits of fasting are underexplored.

Hypothesizing that 1) fasting operates in part through microbiome changes mediating immune system effects and 2) that episodic fasting can potentiate and prime for a shift to a DASH diet, thereby improving its efficacy, a team lead by Dr Sofia Forslund and Professors Dominik Müller and Andreas Michalsen from the DZHK, Max Delbrück Centre, Charité and Immanuel Krankenhaus Berlin recruited a cohort of metabolic syndrome patients randomly assigned to either begin a DASH diet following a 5-day Buchinger fast or to immediately begin a DASH diet. Probands were followed for three months under deep phenotyping, gut microbiome sequencing and immune cell cytometry, followed by bioinformatic analysis to account for changes in antihypertensive medication occurring during the study as proband health improved.

The analysis shows conclusively that episodic fasting induces pervasive microbiome and immune system shifts, which largely reverse after three months on a DASH diet, whereas a DASH diet alone has little impact, supporting a priming influence. Fasting probands substantially reduced blood pressure, need for antihypertensive medication, or both. Long-term responders also show more persistent changes reflecting bloom of gut bacteria with potential to produce anti-inflammatory short-chain fatty acids either during fasting or during refeeding, with concomitant immune system changes.

Responders are possible to identify already pre-intervention through machine learning, and are characterized pre-intervention by reduced abundance of these commensal bacteria, suggesting nutritional interventions can be personalized for maximal efficacy through identifying those with microbiotal and immune deficits the intervention can ameliorate. The DZHK researchers further validated the effects of fasting in a healthy cohort previously described, and will move forward with fasting intervention studies in cohorts for other health conditions.

Link to Paper

Link to Press Release