Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial
Abstract Background On the basis of the contribution of the gut microbiota to hypertension development, a novel strategy involving fecal microbiota transplantation (FMT) has been proposed to treat hypertension, but its efficacy has not been investigated in the clinic. Methods In a randomized, blinde...
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BMC
2025-05-01
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| Online Access: | https://doi.org/10.1186/s40168-025-02118-6 |
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| author | Luyun Fan Junru Chen Qi Zhang Jie Ren Youren Chen Jinfeng Yang Lu Wang Zihong Guo Peili Bu Bingpo Zhu Yanyan Zhao Yang Wang Xiaoyan Liu Wenjie Wang Zhenzhen Chen Qiannan Gao Lemin Zheng Jun Cai |
| author_facet | Luyun Fan Junru Chen Qi Zhang Jie Ren Youren Chen Jinfeng Yang Lu Wang Zihong Guo Peili Bu Bingpo Zhu Yanyan Zhao Yang Wang Xiaoyan Liu Wenjie Wang Zhenzhen Chen Qiannan Gao Lemin Zheng Jun Cai |
| author_sort | Luyun Fan |
| collection | DOAJ |
| description | Abstract Background On the basis of the contribution of the gut microbiota to hypertension development, a novel strategy involving fecal microbiota transplantation (FMT) has been proposed to treat hypertension, but its efficacy has not been investigated in the clinic. Methods In a randomized, blinded, placebo-controlled clinical trial (2021/03–2021/12, ClinicalTrials.gov, NCT04406129), hypertensive patients were recruited from seven centers in China, and received FMT or placebo capsules orally at three visits. The patients were randomized at a 1:1 ratio in blocks of four and stratified by center by an independent statistician. The intention-to-treat principle was implemented, as all randomized participants who received at least one intervention were included. The primary outcome was the decrease in office systolic blood pressure (SBP) from baseline to the day 30 visit. Adverse events (AEs) were recorded through the 3-month follow-up to assess safety measures. Alterations in BP, the fecal microbiome, and the plasma metabolome were assessed via exploratory analyses. Results This study included 124 patients (mean age 43 years, 73.4% men) who received FMT (n = 63) or placebo (n = 61) capsules. The numbers of participants who experienced AEs (13 (20.6%) vs. 9 (14.8%), p = 0.39) and the primary outcome (6.28 (11.83) vs. 5.77 (10.06) mmHg, p = 0.62) were comparable between the groups. The FMT group presented a decrease in SBP after 1 week of FMT, with a between-arm difference of − 4.34 (95% CI, − 8.1 to − 0.58; p = 0.024) mmHg, but this difference did not persist even after repeated intervention. After FMT, shifts in microbial richness and structure were identified and the abundance of the phyla Firmicutes and Bacteroidetes was altered. Decreases in the abundances of Eggerthella lenta, Erysipelatoclostridium ramosum, Anaerostipes hadrus, Gemella haemolysans, and Streptococcus vestibularis and increases in the abundances of Parabacteroides merdae, Prevotella copri, Bacteroides galacturonicus, Eubacterium sp. CAG 180, Desulfovibrio piger, Megamonas hypermegale, Collinsella stercoris, Coprococcus catus, and Allisonella histaminiformans were identified and correlated with office SBP. Those species were also correlated with responding and inversely office SBP-associated metabolites including tyrosine, glutamine, aspartate, phenylalanine, methionine, serine, sarcosine, and/or asparagine. Conclusions Safety but unsustainable BP reduction was observed in the first trial of the effects of FMT on hypertension. Additional intervention studies on specific microbes with metabolite-targeting and BP-modulating features are needed. Video Abstract |
| format | Article |
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| institution | DOAJ |
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| publishDate | 2025-05-01 |
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| series | Microbiome |
| spelling | doaj-art-15c3fc79eaab46b99989d7983c2fcfc82025-08-20T03:08:43ZengBMCMicrobiome2049-26182025-05-0113111810.1186/s40168-025-02118-6Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trialLuyun Fan0Junru Chen1Qi Zhang2Jie Ren3Youren Chen4Jinfeng Yang5Lu Wang6Zihong Guo7Peili Bu8Bingpo Zhu9Yanyan Zhao10Yang Wang11Xiaoyan Liu12Wenjie Wang13Zhenzhen Chen14Qiannan Gao15Lemin Zheng16Jun Cai17Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Chinese Institutes for Medical ResearchState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauThe Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking UniversityShanxi Bethune HospitalDepartment of Cardiology, Second Affiliated Hospital of Shantou University Medical CollegeThe People’s Hospital of Ji Xian DistrictBeijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Chinese Institutes for Medical ResearchFuwai Yunnan Cardiovascular HospitalQilu Hospital of Shandong UniversitySouthern University of Science and Technology HospitalMedical Research & Biometrics Center, National Center for Cardiovascular Dieases, Fuwai Hospital Chinese Academy of Medical SciencesMedical Research & Biometrics Center, National Center for Cardiovascular Dieases, Fuwai Hospital Chinese Academy of Medical SciencesDepartment of Cardiology, Heart Center, Beijing, Key Laboratory of Hypertension Research, Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical UniversityState Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Chinese Institutes for Medical ResearchState Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeReproductive and Genetic Hospital of CITIC-XiangyaBeijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Chinese Institutes for Medical ResearchAbstract Background On the basis of the contribution of the gut microbiota to hypertension development, a novel strategy involving fecal microbiota transplantation (FMT) has been proposed to treat hypertension, but its efficacy has not been investigated in the clinic. Methods In a randomized, blinded, placebo-controlled clinical trial (2021/03–2021/12, ClinicalTrials.gov, NCT04406129), hypertensive patients were recruited from seven centers in China, and received FMT or placebo capsules orally at three visits. The patients were randomized at a 1:1 ratio in blocks of four and stratified by center by an independent statistician. The intention-to-treat principle was implemented, as all randomized participants who received at least one intervention were included. The primary outcome was the decrease in office systolic blood pressure (SBP) from baseline to the day 30 visit. Adverse events (AEs) were recorded through the 3-month follow-up to assess safety measures. Alterations in BP, the fecal microbiome, and the plasma metabolome were assessed via exploratory analyses. Results This study included 124 patients (mean age 43 years, 73.4% men) who received FMT (n = 63) or placebo (n = 61) capsules. The numbers of participants who experienced AEs (13 (20.6%) vs. 9 (14.8%), p = 0.39) and the primary outcome (6.28 (11.83) vs. 5.77 (10.06) mmHg, p = 0.62) were comparable between the groups. The FMT group presented a decrease in SBP after 1 week of FMT, with a between-arm difference of − 4.34 (95% CI, − 8.1 to − 0.58; p = 0.024) mmHg, but this difference did not persist even after repeated intervention. After FMT, shifts in microbial richness and structure were identified and the abundance of the phyla Firmicutes and Bacteroidetes was altered. Decreases in the abundances of Eggerthella lenta, Erysipelatoclostridium ramosum, Anaerostipes hadrus, Gemella haemolysans, and Streptococcus vestibularis and increases in the abundances of Parabacteroides merdae, Prevotella copri, Bacteroides galacturonicus, Eubacterium sp. CAG 180, Desulfovibrio piger, Megamonas hypermegale, Collinsella stercoris, Coprococcus catus, and Allisonella histaminiformans were identified and correlated with office SBP. Those species were also correlated with responding and inversely office SBP-associated metabolites including tyrosine, glutamine, aspartate, phenylalanine, methionine, serine, sarcosine, and/or asparagine. Conclusions Safety but unsustainable BP reduction was observed in the first trial of the effects of FMT on hypertension. Additional intervention studies on specific microbes with metabolite-targeting and BP-modulating features are needed. Video Abstracthttps://doi.org/10.1186/s40168-025-02118-6Fecal microbiota transplantationHypertensionMicrobiomeMetabolome |
| spellingShingle | Luyun Fan Junru Chen Qi Zhang Jie Ren Youren Chen Jinfeng Yang Lu Wang Zihong Guo Peili Bu Bingpo Zhu Yanyan Zhao Yang Wang Xiaoyan Liu Wenjie Wang Zhenzhen Chen Qiannan Gao Lemin Zheng Jun Cai Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial Microbiome Fecal microbiota transplantation Hypertension Microbiome Metabolome |
| title | Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial |
| title_full | Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial |
| title_fullStr | Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial |
| title_full_unstemmed | Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial |
| title_short | Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial |
| title_sort | fecal microbiota transplantation for hypertension an exploratory multicenter randomized blinded placebo controlled trial |
| topic | Fecal microbiota transplantation Hypertension Microbiome Metabolome |
| url | https://doi.org/10.1186/s40168-025-02118-6 |
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