炎症性肠病（IBD）是一类慢性肠道炎症疾病，主要包括克罗恩病和溃疡性结肠炎。原花青素C1（PCC1）是一种从葡萄籽中提取的天然产物，具有明显的抗炎活性。本研究探讨了PCC1用于IBD治疗的潜在用途及其与宿主细胞和微生物相关的机制。利用葡聚糖硫酸钠（DSS）诱导小鼠IBD的经典模型，发现PCC1可以通过保护肠黏膜屏障，从而达到预防IBD的作用。PCC1预处理具有抗炎作用，并改善小鼠IBD模型的多种病理表型，其中包括减少体重减轻情况、降低疾病活动指数（DAI）和增加结肠长度，以及对黏膜屏障有明显保护（如屏障厚度和黏液溶解酶的活性）。自噬标记物微管相关蛋白1轻链3（LC3）结果显示，与非模型组小鼠相比，PCC1预处理组肠道上皮细胞中的LC3表达水平显著升高。PCC1改变了粪便菌群的组成，其中提高了Akkermansia muciniphila和Christensenella minuta的丰度。粪菌移植（FMT）实验结果表明，将PCC1处理过的动物的微生物组移植到PCC1未处理过的动物体内可提供保护作用。代谢谱分析结果表明，PCC1预处理组和FMT组的菌群衍生代谢物戊酸的水平都有所升高。同时，补充这种短链脂肪酸（SCFA）对IBD也起到很好的防治作用。最后，抑制剂实验证实了肠上皮杯状细胞中的FOXO1信号介导戊酸对黏液层的有益作用。综上，PCC1通过改变菌群产生抗炎作用和防治IBD。并且本研究证明了利用多种直接干预措施（如PCC1、FMT和补充戊酸）改善黏膜屏障损伤以治疗IBD的原理可行性。

Inflammatory bowel disease (IBD) refers to a pair of prevalent conditions (Crohn’s disease and ulcerative colitis) distinguished by persistent inflammation of the large intestine. Procyanidin C1 (PCC1) is a naturally occurring substance derived from grape seeds that has demonstrated notable anti-inflammatory properties. This study examines the potential utility of PCC1 as a treatment for IBD and subsequently examines the host-cell- and microbiome-related mechanisms underlying the detected therapeutic benefits. Working with a classic dextran sodium sulfate (DSS)-induced mouse IBD model, we show that PCC1 protects the mucosal barrier and thereby confers strong protective effects against IBD. PCC1 pretreatment resulted in anti-inflammatory effects and protection against multiple pathological phenotypes in the IBD model mice, including reduced weight loss, lower disease activity index (DAI) totals, and enhanced colon size, as well as obviously beneficial effects on the mucosal barrier (e.g., barrier thickness and activity of mucus-degrading enzymes). We also analyzed the autophagy marker microtubule- associated protein1 light chain 3 (LC3) and found that the level of LC3 was significantly elevated in the intestinal epithelial cell samples of the PCC1-pretreatment group as compared with the non-model mice samples. PCC1 altered the fecal microbiome composition, which included elevating the abundance of Akkermansia muciniphila and Christensenella minuta. Fecal microbiome transplant (FMT) experiments showed that delivering a microbiome from PCC1-treated animals into PCC1-naïve animals conferred protection. Metabolic profiling revealed that both the PCC1-pretreatment and PCC1 FMT groups had elevated levels of the microbiota-derived metabolite valeric acid, and supplementation with this short-chain fatty acid (SCFA) also conferred strong protection against IBD. Finally, inhibitor experiments confirmed that the beneficial effects of valeric acid on the mucus layer are mediated by FOXO1 signaling in the goblet cells of the intestinal epithelium. Beyond showing that PCC1 confers anti-inflammatory effects and protection against IBD by altering the microbiome, our study demonstrates proof of principle for multiple straightforward interventions (PCC1, FMT, and valeric acid supplementation) for ameliorating mucosal barrier damage to treat IBD.