Intermittent fasting has shown promise in the management of hypertension, but the mechanistic explanation for this effect remains largely obscure. Studies in experimental animals suggest that intermittent fasting acts on hypertension by modifying the microbiome and particularly by increasing levels of intestinal Bacteroides. Human data, however, are lacking. Here we conducted a clinical trial [ChiCTR2000034646] to investigate the effects of 15-week intermittent fasting on individuals with hypertension. We observe that long-term intermittent fasting effectively counteracts high blood pressure, as demonstrated by significant reduction in systolic blood pressure (144±4.8 [S.E.M.] mmHg at baseline vs. 129±5.6 mmHg at 15 weeks, p=0.004) and diastolic blood pressure (94±5.2 mmHg vs. 79±2.9 mmHg, p=0.005), as well as serum uric acid (410 ± 38 mmol/L at baseline vs. 307 ± 5.5 mmol/L at 15 weeks, p=0.032), which is a strong risk marker for hypertension. Importantly, this effect is associated with significant remodeling of the fecal microbiome (p=0.041). Mirroring earlier data in experimental rodents, we observe a strong inverse correlation between levels of genus Bacteroides and blood pressure (R=-0.608, p=0.04). Our results strongly support the notion that the genus Bacteroides is a major determinant of blood pressure in hypertensive individuals.

Importance While intermittent fasting is generally recognized to be beneficial for patients with high blood pressure, the mechanistic basis for this effect is not resolved. Based on animal data, however, a role of the microbiome and especially the genus Bacteroides has been suggested. Thus prompted, we conducted a clinical trial in hypertensive individuals to link the fecal microbiome to changes in blood pressure. We observed strong correlations between improved blood pressure and fecal levels of the genus Bacteroides. In conjunction with the body of contemporary biomedical literature our data suggest that the effect of intermittent fasting on blood pressure is mediated through Bacteroides opening a novel avenue for rational treatment of this condition.

The authors have declared no competing interest.

ChiCTR2000034646

https://www.chictr.org.cn

This study was partly funded by grant (KICH2.V4P.22.015) of the Dutch Organization for Scientific Research and the Dutch Cancer Foundation.

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The ethics committee of Northwest Minizu University gave ethical approval for this work.

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The sequence data have been deposited with links to BioProject accession No. PRJNA1118570 in the DNA Data Bank of BioProject database (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1118570). Source data of figures is included in the supporting files.