{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:59:38Z","timestamp":1792598378958,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009595","name":"Service Public de Wallonie\u2014Economie, Emploi, Recherche","doi-asserted-by":"publisher","award":["6918"],"award-info":[{"award-number":["6918"]}],"id":[{"id":"10.13039\/501100009595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009595","name":"Service Public de Wallonie\u2014Economie, Emploi, Recherche","doi-asserted-by":"publisher","award":["8225"],"award-info":[{"award-number":["8225"]}],"id":[{"id":"10.13039\/501100009595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gut microbiota alterations are intimately linked to chronic constipation upon aging. We investigated the role of targeted changes in the gut microbiota composition in the relief of constipation symptoms after rhubarb extract (RE) supplementation in middle-aged volunteers. Subjects (95% women, average 58 years old) were randomized to three groups treated with RE at two different doses determined by its content of rhein (supplementation of 12.5 mg and 25 mg per day) vs. placebo (maltodextrin) for 30 days. We demonstrated that daily oral supplementation of RE for 30 days was safe even at the higher dose. Stool frequency and consistency, and perceived change in transit problem, transit speed and difficulty in evacuating, investigated by validated questionnaires, were improved in both groups of RE-treated volunteers compared to placebo. Higher abundance of Lachnospiraceae (mainly Roseburia and Agathobacter) only occurred after RE treatment when present at low levels at baseline, whereas an opposite shift in short-chain fatty acid (SCFA) levels was observed in both RE-treated groups (increase) and placebo (decrease). Fecal Lachnospiraceae and SCFA were positively correlated with stool consistency. This study demonstrates that RE supplementation promotes butyrate-producing bacteria and SCFA, an effect that could contribute to relieving chronic constipation in middle-aged persons.<\/jats:p>","DOI":"10.3390\/ijms232314685","type":"journal-article","created":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T02:05:37Z","timestamp":1669341937000},"page":"14685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Constipation Mitigation by Rhubarb Extract in Middle-Aged Adults Is Linked to Gut Microbiome Modulation: A Double-Blind Randomized Placebo-Controlled Trial"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9435-3338","authenticated-orcid":false,"given":"Audrey M.","family":"Neyrinck","sequence":"first","affiliation":[{"name":"Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6456-329X","authenticated-orcid":false,"given":"Bernard","family":"Taminiau","sequence":"additional","affiliation":[{"name":"Fundamental and Applied Research for Animal and Health (FARAH), Faculty of Veterinary Medicine, University of Li\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Herpin","sequence":"additional","affiliation":[{"name":"CEN Nutriment, Groupe CEN, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-2448","authenticated-orcid":false,"given":"Patrice D.","family":"Cani","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"},{"name":"WELBIO-Walloon Excellence in Life Sciences and Biotechnology, WELBIO Department, WEL Research Institute, 1300 Wavre, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9282-8408","authenticated-orcid":false,"given":"Georges","family":"Daube","sequence":"additional","affiliation":[{"name":"Fundamental and Applied Research for Animal and Health (FARAH), Faculty of Veterinary Medicine, University of Li\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3747-3234","authenticated-orcid":false,"given":"Laure B.","family":"Bindels","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2115-6082","authenticated-orcid":false,"given":"Nathalie M.","family":"Delzenne","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yarullina, D.R., Shafigullin, M.U., Sakulin, K.A., Arzamastseva, A.A., Shaidullov, I.F., Markelova, M.I., Grigoryeva, T.V., Karpukhin, O.Y., and Sitdikova, G.F. (2020). Characterization of gut contractility and microbiota in patients with severe chronic constipation. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235985"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e14050","DOI":"10.1111\/nmo.14050","article-title":"Chronic constipation in adults: Contemporary perspectives and clinical challenges. 1: Epidemiology, diagnosis, clinical associations, pathophysiology and investigation","volume":"33","author":"Scott","year":"2020","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1053\/j.gastro.2013.01.047","article-title":"Complex Interactions Among Diet, Gastrointestinal Transit, and Gut Microbiota in Humanized Mice","volume":"144","author":"Kashyap","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Werth, B.L., and Christopher, S.-A. (2021). Laxative Use in the Community: A Literature Review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10010143"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ajg.2011.349","article-title":"Chronic Constipation in the Elderly","volume":"107","author":"Sterler","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"113096","DOI":"10.1016\/j.jep.2020.113096","article-title":"Topical therapy with rhubarb navel plasters in patients with chronic constipation: Results from a prospective randomized multicenter study","volume":"264","author":"Wei","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"R\u00e9gnier, M., Rastelli, M., Morissette, A., Suriano, F., Le Roy, T., Pilon, G., Delzenne, N.M., Marette, A., Van Hul, M., and Cani, P.D. (2020). Rhubarb Supplementation Prevents Diet-Induced Obesity and Diabetes in Association with Increased Akkermansia muciniphila in Mice. Nutrients, 12.","DOI":"10.3390\/nu12102932"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1500899","DOI":"10.1002\/mnfr.201500899","article-title":"Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake, an effect related to the modulation of the gut microbiota","volume":"61","author":"Neyrinck","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jada.2009.03.012","article-title":"Adherence to the French Programme National Nutrition Sant\u00e9 Guideline Score Is Associated with Better Nutrient Intake and Nutritional Status","volume":"109","author":"Estaquio","year":"2009","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mohtashami, L., Amiri, M.S., Ayati, Z., Ramezani, M., Jamialahmadi, T., Emami, S.A., and Sahebkar, A. (2021). Ethnobotanical Uses, Phytochemistry and Pharmacology of Different Rheum Species (Polygonaceae): A Review. Pharmacological Properties of Plant-Derived Natural Products and Implications for Human Health, Springer International Publishing.","DOI":"10.1007\/978-3-030-64872-5_22"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1016\/j.apmr.2015.08.411","article-title":"Cross-Sectional Study of Bowel Symptoms in Adults With Cerebral Palsy: Prevalence and Impact on Quality of Life","volume":"96","author":"Marciniak","year":"2015","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/j.1365-2036.2010.04273.x","article-title":"Systematic review: Impact of constipation on quality of life in adults and children","volume":"31","author":"Belsey","year":"2010","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/MCG.0000000000001385","article-title":"Effects of Lubiprostone, an Intestinal Secretagogue, on Electrolyte Homeostasis in Chronic Idiopathic and Opioid-induced Constipation","volume":"55","author":"Rao","year":"2020","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1155\/MI.2005.175","article-title":"Serum Levels of the MCP-1 Chemokine in Patients With Ischemic Stroke and Myocardial Infarction","volume":"2005","author":"Arakelyan","year":"2005","journal-title":"Mediat. Inflamm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"140","DOI":"10.5056\/jnm.2011.17.2.140","article-title":"Microflora Modulation of Motility","volume":"17","author":"Quigley","year":"2011","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.bpg.2011.01.003","article-title":"The enteric microbiota in the pathogenesis and management of constipation","volume":"25","author":"Quigley","year":"2011","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.dld.2005.06.008","article-title":"Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation","volume":"37","author":"Khalif","year":"2005","journal-title":"Dig. Liver Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fmed.2019.00019","article-title":"Gut Microbiota and Chronic Constipation: A Review and Update","volume":"6","author":"Ohkusa","year":"2019","journal-title":"Front. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1152\/physiolgenomics.00082.2014","article-title":"Structural changes in the gut microbiome of constipated patients","volume":"46","author":"Zhu","year":"2014","journal-title":"Physiol. Genom."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e1801187","DOI":"10.1002\/mnfr.201801187","article-title":"Abundance of Probiotics and Butyrate-Production Microbiome Manages Constipation via Short-Chain Fatty Acids Production and Hormones Secretion","volume":"63","author":"Zhuang","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1007\/s00253-022-11813-5","article-title":"Targeting intestinal flora and its metabolism to explore the laxative effects of rhubarb","volume":"106","author":"Yang","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s00284-022-02811-x","article-title":"Rhubarb alleviates acute lung injury by modulating gut microbiota dysbiosis in mice","volume":"79","author":"Tang","year":"2022","journal-title":"Curr. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jalanka, J., Major, G., Murray, K., Singh, G., Nowak, A., Kurtz, C., Silos-Santiago, I., Johnston, J.M., de Vos, W.M., and Spiller, R. (2019). The Effect of Psyllium Husk on Intestinal Microbiota in Constipated Patients and Healthy Controls. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020433"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Vacca, M., Celano, G., Calabrese, F.M., Portincasa, P., Gobbetti, M., and De Angelis, M. (2020). The controversial role of human gut lachnospiraceae. Microorganisms, 8.","DOI":"10.3390\/microorganisms8040573"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jep.2013.12.055","article-title":"Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract","volume":"152","author":"Kon","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","first-page":"369","article-title":"Acceleration of large intestine transit time in rats by sennosides and related compounds","volume":"38","year":"1986","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1136\/gut.29.9.1180","article-title":"Changes in colonic motility induced by sennosides in dogs: Evidence of a prostaglandin mediation","volume":"29","author":"Staumont","year":"1988","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jpainsymman.2008.04.016","article-title":"A Review of the Literature on Gender and Age Differences in the Prevalence and Characteristics of Constipation in North America","volume":"37","author":"McCrea","year":"2009","journal-title":"J. Pain Symptom Manag."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1097\/MCO.0b013e32832e6776","article-title":"The impact of physical exercise on the gastrointestinal tract","volume":"12","author":"Burini","year":"2009","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"920","DOI":"10.3109\/00365529709011203","article-title":"Stool Form Scale as a Useful Guide to Intestinal Transit Time","volume":"32","author":"Lewis","year":"1997","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1186\/s13063-018-2648-x","article-title":"The effects of Bifidobacterium animalis ssp. lactis B94 on gastrointestinal wellness in adults with Prader-Willi syndrome: Study protocol for a randomized controlled trial","volume":"19","author":"Alyousif","year":"2018","journal-title":"Trials"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.eurpsy.2018.05.006","article-title":"Patient centric measures for a patient centric era: Agreement and convergent between ratings on The Patient Global Impression of Improvement (PGI-I) scale and the Clinical Global Impressions\u2013Improvement (CGI-S) scale in bipolar and major depressive disorder","volume":"53","author":"Mohebbi","year":"2018","journal-title":"Eur. Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1186\/s12955-018-1049-x","article-title":"A patient-reported pressure ulcer health-related quality of life instrument for use in prevention trials (PU-QOL-P): Psychometric evaluation","volume":"16","author":"Rutherford","year":"2018","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Aoun, S.M., Deas, K., Howting, D., and Lee, G. (2015). Exploring the Support Needs of Family Caregivers of Patients with Brain Cancer Using the CSNAT: A Comparative Study with Other Cancer Groups. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145106"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jchromb.2019.06.013","article-title":"Development of an analytical method to detect short-chain fatty acids by SPME-GC\u2013MS in samples coming from an in vitro gastrointestinal model","volume":"1124","author":"Douny","year":"2019","journal-title":"J. Chromatogr. B"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14685\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:26:07Z","timestamp":1760145967000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":35,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232314685"],"URL":"https:\/\/doi.org\/10.3390\/ijms232314685","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]}}}