Kombucha Prevents Indomethacin‐Induced Enteric Damage in Wistar Rat by Enhancing Epithelial Gut Barrier and Modulating Gut Microbiota

Kombucha is a fermented beverage with high contents of antioxidants and probiotics. Enteric damage due to uncontrolled consumption of non-steroidal anti-inflammatory drugs (NSAIDs) represents a significant cause of morbidity and mortality. This study aimed to evaluate the preventive effects of kombucha against indomethacin-induced enteric damage. Wistar rats were divided into control (Ctrl), supplemented with kombucha (Komb), indomethacin-induced enteric damage (Indo), and indomethacin-induced enteric damage and supplemented with kombucha (Indo-Komb) groups. We analyzed ulcer index, histological changes, gene expression of intestinal barrier function genes, and microbiota phyla in cecal content. Kombucha supplementation reduced ulcer index and intestinal inflammation, which improved survival (<i>p</i> = 0.0291), maintained body weight, (<i>p</i> < 0.001) and avoided the drop in levels of hemoglobin, hematocrit, and erythrocytes (<i>p</i> < 0.001). Histopathological analyses of intestines revealed impaired integrity of villi with inflammatory infiltrates, which were significantly prevented with kombucha supplementation (<i>p</i> = 0.0024 and <i>p</i> = 0.0017, respectively). Rats that received kombucha upregulated the expression of tight junction genes <i>Muc2</i>, <i>Cldn1</i>, and <i>Ocln</i> (<i>p</i> = 0.027, <i>p</i> = 0.024, <i>p</i> < 0.001, respectively). The upregulation of the oxidative and inflammatory markers <i>Nos2</i>, <i>Mpo</i>, and <i>Tnf</i> was prevented by kombucha intake (<i>p</i> < 0.001). Additionally, kombucha ameliorated the dysbiosis in indomethacin-induced enteric damaged rats by reduction of <i>Proteobacteria</i> (<i>p</i> < 0.001) while increasing <i>Firmicutes</i> abundance. This study demonstrated that kombucha consumption is a viable strategy to delay NSAID-induced enteric damage through enhancement of intestinal barrier integrity and prevention of dysbiosis.