Fecal Microbiota Transplantation on Hypertension: an exploratory, multi-center, randomized, blinded, placebo-controlled trial

Background: Along with contribution of gut microbiota on hypertension established, novel strategy of fecal microbiota transplantation(FMT) on hypertension treatment has been proposed and yet to be investigated in clinic. Methods: A randomized, blinded, placebo-controlled clinical trial (2021/03-2021/12, ClinicalTrials.gov, NCT04406129) recruited hypertension patients from seven centers in China, orally receiving FMT or placebo capsules via three visits. Randomization was performed at a 1:1 ratio in blocks of four and stratified by center, by independent statistician. Intention-to-treat principle including all randomized participants with at least one intervention was implemented. Primary outcome was office systolic blood pressure(SBP) decreasing from baseline to day 30 visit. Adverse events(AEs) as safety measures were evaluated through three-month follow up. Alterations were assessed in BP measures, fecal microbiome and plasma metabolome as exploratory analysis. Findings: This study recruited 124 patients(mean age 43 years, 73.4% men) receiving FMT (n=63) and placebo (n=61) capsules, respectively. Participants with DOOTE AEs(13(20.6%) vs 9(14.8%), p=0.39) and primary outcome(6.28(11.83) vs 5.77(10.06) mmHg, p=0.62) were comparable between groups. One-week SBP reduction after FMT was explored with between-arm difference of -4.34(95% CI, -8.1 to -0.58, p=0.024) mmHg but cannot persist even after repeated intervention. Shifts on microbial richness and structure were identified with recovered phyla of Firmicutes and Bacterioidetes. Responding species and metabolites correlated with SBP were identified of Eggerthella lenta, Erysipelatoclostridium ramosum, Anaerostipes hadrus, Gemella haemolysans, Streptococcus vestibularis,Parabacteroides merdae, Prevotella copri, Bacteroides galacturonicus, Eubacterium sp CAG 180, Desulfovibrio piger, Megamonas hypermegale, Collinsella stercoris, Coprococcus catus, Allisonella histaminiformans, and tyrosine, glutamine, aspartate, phenylalanine, methionine, serine, sarcosine, asparagine. Interpretation: Safety but unsustainable BP reduction is observed of in the first trial of FMT on hypertension. Additional studies on intervening specific microbes with metabolite-targeting and BP-modulating features are needed.