Low-Molecular-Weight Fraction of Ripe Pu-erh Tea Protects against Alcohol-Induced Gastric Injury via Gut Microbiota-Dependent Modulation.

Excessive alcohol intake is a major cause of acute alcoholic gastric injury (AGI), yet effective dietary preventive strategies remain limited. Here, ripe Pu-erh tea extract was fractionated into three membrane-separated fractions (T1-T3) and evaluated in preventive and therapeutic mouse models of AGI. The low-molecular-weight fraction T3 (<300 kDa), obtained using a 50 nm ceramic membrane, exhibited the strongest gastroprotective activity, with preventive efficacy exceeding therapeutic efficacy, highlighting the value of early intervention. Preventive T3 administration alleviated gastric mucosal injury, restored PGE2 levels, attenuated inflammation and oxidative stress, and improved intestinal barrier function. These effects were accompanied by gut microbiota remodeling, including enrichment of Dubosiella and Bifidobacterium and increased butyrate production. Antibiotic-mediated microbiota depletion attenuated T3 efficacy, supporting a microbiota-dependent mechanism. Serum metabolomics further indicated regulation of glutathione-related pathways. Overall, T3 represents a promising low-molecular-weight fraction of Pu-erh tea for dietary prevention of AGI through modulation of microbiota-gut-stomach homeostasis.