{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:26:38Z","timestamp":1790364398338,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Surgery, Oncology, and Gastroenterology, University of Padua","award":["SID-UniPD"],"award-info":[{"award-number":["SID-UniPD"]}]},{"name":"Distillerie Bonollo Umberto SPA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Recent research highlights Vitis vinifera seeds as a rich source of bioactive proanthocyanidins (PACs) with antioxidant and immunomodulatory effects. Poorly absorbed PACs are metabolized by gut microbiota into active phenolic metabolites. This pilot study in ulcerative colitis patients assessed grape seed extract effects on microbiota, zonulin-related permeability, and quality of life. Methods: This prospective pilot study, conducted at the University Hospital of Padua, evaluated the effects of an eight-week treatment with proanthocyanidins (ECOVITIS\u00ae) on gut microbiota, intestinal permeability (zonulin), and well-being in patients with ulcerative colitis in remission (IBDQ). Fecal and serum samples were collected at T0 and T1. Microbiota analysis was performed through 16S rRNA gene sequencing (QIIME2), zonulin was quantified using an ELISA kit for pre-haptoglobin gene2 (pre-HP2), and HP1\/HP2 genotyping was conducted by quantitative PCR. Statistical analyses (Wilcoxon, ALDEx2, PERMANOVA) assessed microbial diversity and taxonomic changes between pre- and post-treatment samples. Results: Twenty-five ulcerative colitis patients completed the study. IBDQ scores significantly improved after treatment (mean \u0394 = +11.2, p &lt; 0.001), especially in the 11 best IBDQ responders (\u0394 = +24.2, p &lt; 0.001). Microbiota analysis showed increased Lachnospiraceae and Sutterellaceae in responders, while overall diversity remained unchanged. Zonulin levels were unaffected. Conclusions: PAC treatment improved quality of life in ulcerative colitis patients, as shown by increased IBDQ scores. Serum zonulin levels remained unchanged. Microbiota analysis revealed enrichment of Lachnospiraceae and Sutterellaceae families, suggesting beneficial modulation. Limitations include lack of metabolic assessment and a control group, and caution is needed in interpreting zonulin measurements.<\/jats:p>","DOI":"10.3390\/jcm15020888","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:21:40Z","timestamp":1769505700000},"page":"888","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protective Effects of Grapeseed Proanthocyanidins in Ulcerative Colitis: A Pilot Study Evaluating a Potential Therapeutic Strategy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-590X","authenticated-orcid":false,"given":"Sonia","family":"Facchin","sequence":"first","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, 35128 Padua, Italy"},{"name":"Gastroenterology Unit, Azienda Ospedale Universit\u00e0 di Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Agostini","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Azienda Ospedale Universit\u00e0 di Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Laparra-Ruiz","sequence":"additional","affiliation":[{"name":"BMR Genomics S.R.L., Via Redipuglia 22, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9147-4946","authenticated-orcid":false,"given":"Giuseppe","family":"Benvenuto","sequence":"additional","affiliation":[{"name":"BMR Genomics S.R.L., Via Redipuglia 22, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Valle","sequence":"additional","affiliation":[{"name":"BMR Genomics S.R.L., Via Redipuglia 22, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9816-4171","authenticated-orcid":false,"given":"Luisa","family":"Bertin","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3187-2894","authenticated-orcid":false,"given":"Edoardo Vincenzo","family":"Savarino","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, 35128 Padua, Italy"},{"name":"Gastroenterology Unit, Azienda Ospedale Universit\u00e0 di Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108999","DOI":"10.1016\/j.biopha.2019.108999","article-title":"Proanthocyanidins: A Comprehensive Review","volume":"116","author":"Rauf","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1089\/jmf.2008.0096","article-title":"Biological and Medicinal Properties of Grapes and Their Bioactive Constituents: An Update","volume":"12","author":"Yadav","year":"2009","journal-title":"J. Med. Food"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.jada.2011.05.015","article-title":"The Effect of Grape Seed Extract on Cardiovascular Risk Markers: A Meta-Analysis of Randomized Controlled Trials","volume":"111","author":"Feringa","year":"2011","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/biof.79","article-title":"Healthy Properties of Proanthocyanidins","volume":"36","author":"Milagro","year":"2010","journal-title":"Biofactors"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/ptr.6518","article-title":"The Effects of Grape Seed Extract on Glycemic Control, Serum Lipoproteins, Inflammation, and Body Weight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"34","author":"Asbaghi","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sochorova, L., Prusova, B., Jurikova, T., Mlcek, J., Adamkova, A., Baron, M., and Sochor, J. (2020). The Study of Antioxidant Components in Grape Seeds. Molecules, 25.","DOI":"10.3390\/molecules25163736"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e1800819","DOI":"10.1002\/mnfr.201800819","article-title":"The Human Metabolism of Nuts Proanthocyanidins Does Not Reveal Urinary Metabolites Consistent with Distinctive Gut Microbiota Metabotypes","volume":"63","author":"Selma","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100617","DOI":"10.1016\/j.fbio.2020.100617","article-title":"Characterization and Bioactivity of Proanthocyanidins during Malay Cherry (Lepisanthes alata) Fruit Ripening","volume":"36","author":"Zhang","year":"2020","journal-title":"Food Biosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1080\/10408398.2017.1418284","article-title":"Proanthocyanidins in Cereals and Pseudocereals","volume":"59","author":"Zhu","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Morazzoni, P., Vanzani, P., Santinello, S., Gucciardi, A., Zennaro, L., Miotto, G., and Ursini, F. (2021). Grape Seeds Proanthocyanidins: Advanced Technological Preparation and Analytical Characterization. Antioxidants, 10.","DOI":"10.3390\/antiox10030418"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3986","DOI":"10.1039\/D0FO00350F","article-title":"Bioavailability of Red Wine and Grape Seed Proanthocyanidins in Rats","volume":"11","author":"Gaillet","year":"2020","journal-title":"Food Funct."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Andersen-Civil, A.I.S., Arora, P., and Williams, A.R. (2021). Regulation of Enteric Infection and Immunity by Dietary Proanthocyanidins. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.637603"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102981","DOI":"10.1016\/j.redox.2023.102981","article-title":"Unraveling the Parahormetic Mechanism Underlying the Health-Protecting Effects of Grapeseed Procyanidins","volume":"69","author":"Baron","year":"2024","journal-title":"Redox Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1590\/s0004-2803.202202000-43","article-title":"Factors Associated with Circulating Zonulin in Inflammatory Bowel Disease","volume":"59","author":"Lacombe","year":"2022","journal-title":"Arq. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16799","DOI":"10.1073\/pnas.0906773106","article-title":"Identification of Human Zonulin, a Physiological Modulator of Tight Junctions, as Prehaptoglobin-2","volume":"106","author":"Tripathi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0002-9440(10)62319-X","article-title":"Plasma Protein Haptoglobin Modulates Renal Iron Loading","volume":"166","author":"Fagoonee","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1134\/S1990750821030069","article-title":"Haptoglobin as a Biomarker","volume":"15","author":"Naryzny","year":"2021","journal-title":"Biochem. Moscow Suppl. Ser. B"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"22462","DOI":"10.1038\/s41598-021-01879-y","article-title":"Novel Role of Zonulin in the Pathophysiology of Gastro-Duodenal Transit: A Clinical and Translational Study","volume":"11","author":"Martinez","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.cgh.2012.08.012","article-title":"Intestinal Permeability and Its Regulation by Zonulin: Diagnostic and Therapeutic Implications","volume":"10","author":"Fasano","year":"2012","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_20","first-page":"171","article-title":"The role of anti-TNF therapy in ulcerative colitis","volume":"67","author":"Urek","year":"2013","journal-title":"Acta Med. Croatica"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/ecco-jcc\/jjab177","article-title":"ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment","volume":"16","author":"Spinelli","year":"2022","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.dld.2010.12.014","article-title":"Validation of the Italian Translation of the Inflammatory Bowel Disease Questionnaire","volume":"43","author":"Ciccocioppo","year":"2011","journal-title":"Dig. Liver Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/309131a0","article-title":"Duplication within the Haptoglobin Hp2 Gene","volume":"309","author":"Maeda","year":"1984","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1373\/clinchem.2008.113126","article-title":"TaqMan-Based Real-Time PCR for Genotyping Common Polymorphisms of Haptoglobin (HP1 and HP2)","volume":"54","author":"Soejima","year":"2008","journal-title":"Clin. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing Real-Time PCR Data by the Comparative C(T) Method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Barandouzi, Z.A., Starkweather, A.R., Henderson, W.A., Gyamfi, A., and Cong, X.S. (2020). Altered Composition of Gut Microbiota in Depression: A Systematic Review. Front. Psychiatry, 11.","DOI":"10.3389\/fpsyt.2020.00541"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jiang, D., Goswami, R., Dennis, M., Heimsath, H., Kozlowski, P.A., Ardeshir, A., Van Rompay, K.K.A., De Paris, K., Permar, S.R., and Surana, N.K. (2023). Sutterella and Its Metabolic Pathways Positively Correlate with Vaccine-Elicited Antibody Responses in Infant Rhesus Macaques. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1283343"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108116","DOI":"10.1016\/j.diabres.2020.108116","article-title":"The Genus Sutterella Is a Potential Contributor to Glucose Metabolism Improvement after Roux-En-Y Gastric Bypass Surgery in T2D","volume":"162","author":"Wang","year":"2020","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13592","DOI":"10.1021\/acs.jafc.2c03464","article-title":"Study on the Interaction between Four Typical Carotenoids and Human Gut Microflora Using an in Vitro Fermentation Model","volume":"70","author":"Dai","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.immuni.2025.02.003","article-title":"Bile Acid Receptor FXR Promotes Intestinal Epithelial Ferroptosis and Subsequent ILC3 Dysfunction in Neonatal Necrotizing Enterocolitis","volume":"58","author":"Zhang","year":"2025","journal-title":"Immunity"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e70277","DOI":"10.1111\/liv.70277","article-title":"Role of Gut-Derived Endotoxins in Porto-Sinusoidal Vascular Disorder: Comparison Between Patients with and without Portal Hypertension","volume":"45","author":"Overi","year":"2025","journal-title":"Liver Int."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bagnato, C., Magna, A., Mereu, E., Bernardini, S., Bartimoccia, S., Marti, R., Lazzerini, P.E., D\u2019Amico, A., Ettorre, E., and Desideri, G. (2025). Impact of Hospitalization on Sarcopenia, NADPH-Oxidase 2, Oxidative Stress, and Low-Grade Endotoxemia in Elderly Patients. Antioxidants, 14.","DOI":"10.3390\/antiox14030304"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1080\/00365521.2021.1879247","article-title":"Colonic Paracellular Permeability and Circulating Zonulin-Related Proteins","volume":"56","author":"Bednarska","year":"2021","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Scheffler, L., Crane, A., Heyne, H., T\u00f6njes, A., Schleinitz, D., Ihling, C.H., Stumvoll, M., Freire, R., Fiorentino, M., and Fasano, A. (2018). Widely Used Commercial ELISA Does Not Detect Precursor of Haptoglobin2, but Recognizes Properdin as a Potential Second Member of the Zonulin Family. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00022"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ajamian, M., Steer, D., Rosella, G., and Gibson, P.R. (2019). Serum Zonulin as a Marker of Intestinal Mucosal Barrier Function: May Not Be What It Seems. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0210728"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Power, N., Turpin, W., Espin-Garcia, O., Smith, M.I., CCC GEM Project Research Consortium, and Croitoru, K. (2021). Serum Zonulin Measured by Commercial Kit Fails to Correlate with Physiologic Measures of Altered Gut Permeability in First Degree Relatives of Crohn\u2019s Disease Patients. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.645303"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e27321","DOI":"10.4161\/tisb.27321","article-title":"The Role of Haptoglobin and Its Related Protein, Zonulin, in Inflammatory Bowel Disease","volume":"1","author":"Vanuytsel","year":"2013","journal-title":"Tissue Barriers"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/2\/888\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:29:46Z","timestamp":1769506186000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/2\/888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["jcm15020888"],"URL":"https:\/\/doi.org\/10.3390\/jcm15020888","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]}}}