Protective Effects of Grapeseed Proanthocyanidins in Ulcerative Colitis: A Pilot Study Evaluating a Potential Therapeutic Strategy

<b>Background/Objectives</b>: Recent research highlights <i>Vitis vinifera</i> 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. <b>Methods</b>: This prospective pilot study, conducted at the University Hospital of Padua, evaluated the effects of an eight-week treatment with proanthocyanidins (ECOVITIS^®) 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. <b>Results</b>: Twenty-five ulcerative colitis patients completed the study. IBDQ scores significantly improved after treatment (mean Δ = +11.2, <i>p</i> < 0.001), especially in the 11 best IBDQ responders (Δ = +24.2, <i>p</i> < 0.001). Microbiota analysis showed increased <i>Lachnospiraceae</i> and <i>Sutterellaceae</i> in responders, while overall diversity remained unchanged. Zonulin levels were unaffected. <b>Conclusions:</b> 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 <i>Lachnospiraceae</i> and <i>Sutterellaceae</i> families, suggesting beneficial modulation. Limitations include lack of metabolic assessment and a control group, and caution is needed in interpreting zonulin measurements.