{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:02:12Z","timestamp":1785733332697,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["15161391"],"award-info":[{"award-number":["15161391"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Dietary intake of fermented soymilk is associated with hypotensive effects, but the mechanisms involved have not been fully elucidated. We investigated the anti-hypertensive effects of soymilk fermented by L. rhamnosus AC1 on DOCA-salt hypertension from the point of view of oxidative stress, inflammatory response and alteration of the gut microbiome. The antioxidant assays in vitro indicated the ethanol extract (EE) of L. rhamnosus AC1 fermented soymilk showed better antioxidative effects than the water extract (WE). Those extracts displayed a hypotensive effect using a tail-cuff approach to measuring blood pressure and improved nitric oxide (NO), angiotensin II (Ang II), tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin factor-6 (IL-6) on DOCA-salt hypertensive rats. Furthermore, cardiac and renal fibrosis were attenuated by those extracts. The gut microbiota analysis revealed that they significantly reduced the abundance of phylum Proteobacteria, its family Enterobacteriaceae and genus Escherichia-Shigella. Moreover, metabolomic profiling revealed several potential gut microbiota-related metabolites which appeared to involve in the development and recovery of hypertension. In conclusion, fermented soymilk is a promising nutritional intervention strategy to improve hypertension via reducing inflammation and reverting dysbiotic microbiota.<\/jats:p>","DOI":"10.3390\/nu14153174","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:15:26Z","timestamp":1659485726000},"page":"3174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Elucidation of Anti-Hypertensive Mechanism by a Novel Lactobacillus rhamnosus AC1 Fermented Soymilk in the Deoxycorticosterone Acetate-Salt Hypertensive Rats"],"prefix":"10.3390","volume":"14","author":[{"given":"Haicui","family":"Wu","sequence":"first","affiliation":[{"name":"Shenzhen Key Lab for Food Biological Safety Control, Hong Kong PolyU Shen Zhen Research Institute, Shenzhen 518000, China"},{"name":"Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China"},{"name":"Research Institute for Future Food, The Hong Kong Polytechnic University, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4149-2983","authenticated-orcid":false,"given":"Tim-Fat","family":"Shum","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China"},{"name":"Research Institute for Future Food, The Hong Kong Polytechnic University, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8306-1826","authenticated-orcid":false,"given":"Jiachi","family":"Chiou","sequence":"additional","affiliation":[{"name":"Shenzhen Key Lab for Food Biological Safety Control, Hong Kong PolyU Shen Zhen Research Institute, Shenzhen 518000, China"},{"name":"Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China"},{"name":"Research Institute for Future Food, The Hong Kong Polytechnic University, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1097\/00004872-200401000-00003","article-title":"Worldwide prevalence of hypertension: A systematic review","volume":"22","author":"Kearney","year":"2004","journal-title":"J. Hypertens."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.annemergmed.2007.11.004","article-title":"Pathophysiology of hypertension","volume":"51","author":"Heilpern","year":"2008","journal-title":"Ann. Emerg. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1589\/jpts.27.303","article-title":"A review of deoxycorticosterone acetate-salt hypertension and its relevance for cardiovascular physiotherapy research","volume":"27","author":"Lee","year":"2015","journal-title":"J. Phys. Ther. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2174\/157340310793566109","article-title":"The DOCA-Salt Hypertensive Rat as a Model of Cardiovascular Oxidative and Inflammatory Stress","volume":"6","author":"Iyer","year":"2010","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1161\/01.HYP.0000202568.01167.B6","article-title":"American Heart Association. Dietary approaches to prevent and treat hypertension: A scientific statement from the American Heart Association","volume":"47","author":"Appel","year":"2006","journal-title":"Hypertension"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10484-006-9004-8","article-title":"The efficacy of behavioral treatments for hypertension","volume":"31","author":"Linden","year":"2006","journal-title":"Appl. Psychophysiol. Biofeedback"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/abm\/16.1.35","article-title":"Clinical effectiveness of non-drug treatment for hypertension: A meta-analysis","volume":"16","author":"Linden","year":"1994","journal-title":"Ann. Behav. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1574-6968.1990.tb04887.x","article-title":"Health and nutritional benefits from lactic acid bacteria","volume":"7","author":"Gilliland","year":"1990","journal-title":"FEMS. Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1002\/jsfa.5880","article-title":"The effect of probiotic-fermented soy milk on enhancing the NO-mediated vascular relaxation factors","volume":"93","author":"Cheng","year":"2013","journal-title":"J. Sci. Food Agric."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/sj.embor.7400731","article-title":"The gut flora as a forgotten organ","volume":"7","author":"Shanahan","year":"2006","journal-title":"EMBO Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1053\/j.gastro.2014.03.001","article-title":"The intestinal metabolome: An intersection between microbiota and host","volume":"146","author":"Ursell","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/4441022a","article-title":"Microbial ecology: Human gut microbes associated with obesity","volume":"444","author":"Ley","year":"2006","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1038\/ismej.2012.43","article-title":"Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans","volume":"6","author":"Sanapareddy","year":"2012","journal-title":"ISME J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1002\/hep.20194","article-title":"Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis","volume":"39","author":"Liu","year":"2004","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Maeda, Y., and Takeda, K. (2017). Role of Gut Microbiota in Rheumatoid Arthritis. J. Clin. Med., 6.","DOI":"10.3390\/jcm6060060"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature11450","article-title":"A metagenome-wide association study of gut microbiota in type 2 diabetes","volume":"490","author":"Qin","year":"2012","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1097\/MNH.0000000000000149","article-title":"Gut microbiota in hypertension","volume":"4","author":"Jose","year":"2015","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wu, H., Shum, T.F., and Chiou, J. (2021). Characterization of the Probiotic Potential of Lactic Acid Bacteria Isolated from Kimchi, Yogurt, and Baby Feces in Hong Kong and Their Performance in Soymilk Fermentation. Microorganisms, 9.","DOI":"10.3390\/microorganisms9122544"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41440-021-00796-x","article-title":"Hypotensive effect of captopril on deoxycorticosterone acetate-salt-induced hypertensive rat is associated with gut microbiota alteration","volume":"45","author":"Wu","year":"2021","journal-title":"Hypertens. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5853238","DOI":"10.1155\/2017\/5853238","article-title":"Oxidative Stress and Inflammation in Cardiovascular Disease","volume":"2017","author":"Zazueta","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Koliada, A., Syzenko, G., Moseiko, V., Budovska, L., Puchkov, K., Perederiy, V., Gavalko, Y., Dorofeyev, A., Romanenko, M., and Tkach, S. (2017). Association between body mass index and Firmicutes\/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiol., 17.","DOI":"10.1186\/s12866-017-1027-1"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e13443","DOI":"10.14814\/phy2.13443","article-title":"Gut inflammation and dysbiosis in human motor neuron disease","volume":"5","author":"Rowin","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1161\/HYPERTENSIONAHA.115.05315","article-title":"Gut dysbiosis is linked to hypertension","volume":"65","author":"Yang","year":"2015","journal-title":"Hypertension"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40168-016-0222-x","article-title":"Gut microbiota dysbiosis contributes to the development of hypertension","volume":"5","author":"Li","year":"2017","journal-title":"Microbiome"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1152\/physiol.00026.2016","article-title":"The Hypertension Pandemic: An Evolutionary Perspective","volume":"32","author":"Rossier","year":"2017","journal-title":"Physiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s11906-017-0731-4","article-title":"DOCA-Salt Hypertension: An Update","volume":"19","author":"Basting","year":"2017","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_27","first-page":"88","article-title":"Malignant Hypertension Produced by Treatment with Desoxycorticosterone Acetate and Sodium Chloride","volume":"49","author":"Selye","year":"1943","journal-title":"Can. Med. Assoc. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1161\/01.RES.36.2.300","article-title":"Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: Role of renin and sodium in vascular changes","volume":"36","author":"Gavras","year":"1975","journal-title":"Circ. Res."},{"key":"ref_29","first-page":"75","article-title":"Interrelationships of sodium intake, hypertension, and norepinephrine storage in the rat","volume":"24","author":"Krakoff","year":"1969","journal-title":"Circ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/ajh\/6.6.487","article-title":"Myocardial fibrosis in the rat with mineralocorticoid excess. Prevention of scarring by amiloride","volume":"6","author":"Campbell","year":"1993","journal-title":"Am. J. Hypertens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/01.RES.20.1.136","article-title":"Catecholamine metabolism in experimental hypertension in the rat","volume":"20","author":"Krakoff","year":"1967","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/BF02889368","article-title":"Deveolpment of hypertension in rats maintained on a sodium deficient diet and bearing a mammotropic tumor (MtTF4)","volume":"19","author":"Molteni","year":"1975","journal-title":"Virchows Arch. B Cell Pathol."},{"key":"ref_33","first-page":"S143","article-title":"Reversal of cardiac fibrosis in deoxycorticosterone acetate-salt hypertensive rats by inhibition of the renin-angiotensin system","volume":"10","author":"Brown","year":"1999","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1152\/physiolgenomics.00081.2016","article-title":"Alterations in the gut microbiota can elicit hypertension in rats","volume":"49","author":"Adnan","year":"2017","journal-title":"Physiol. Genom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s11906-017-0734-1","article-title":"The Gut, Its Microbiome, and Hypertension","volume":"19","author":"Richards","year":"2017","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"894","DOI":"10.3168\/jds.S0022-0302(00)74953-8","article-title":"Probiotic bacteria: Selective enumeration and survival in dairy foods","volume":"83","author":"Shah","year":"2000","journal-title":"J. Dairy Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wildman, R. (2016). Handbook of Nutraceuticals and Functional Foods, CRC Press. [2nd ed.].","DOI":"10.1201\/9781420006186"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1111\/j.1365-2621.2002.tb08866.x","article-title":"Enzymic Transformation of Isoflavone Phytoestrogens in Soymilk by \u03b2-Glucosidase-Producing Bifidobacteria","volume":"67","author":"Tsangalis","year":"2002","journal-title":"J. Food Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.fm.2005.01.020","article-title":"Antioxidative activities of soymilk fermented with lactic acid bacteria and bifidobacteria","volume":"23","author":"Wang","year":"2006","journal-title":"Food Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ijfoodmicro.2006.04.034","article-title":"Mutagenicity and antimutagenic effect of soymilk fermented with lactic acid bacteria and bifidobacteria","volume":"111","author":"Hsieh","year":"2006","journal-title":"Int. J. Food Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e003698","DOI":"10.1161\/JAHA.116.003698","article-title":"Gut Microbiota Promote Angiotensin II-Induced Arterial Hypertension and Vascular Dysfunction","volume":"5","author":"Karbach","year":"2016","journal-title":"J. Am. Heart Assoc."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/15\/3174\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:01:06Z","timestamp":1760140866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/15\/3174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,2]]},"references-count":41,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["nu14153174"],"URL":"https:\/\/doi.org\/10.3390\/nu14153174","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,2]]}}}