FMT and Bifidobacterium quadruple viable tablets supplementation modulate gut microbiota to ameliorate high-altitude exposure induced colonic injury.

High-altitude hypoxic environments can induce significant gut microbiota dysbiosis, which in turn triggers colonic inflammation and intestinal barrier injury. This study aims to elucidate the core driving role of the gut microbiota in high-altitude induced colonic injury and to verify the protective effects of Bifidobacterium quadruple viable tablets (BQT). Here, we exposed C57BL/6 mice to acute and subacute exposure in high-altitude environment. High-altitude hypoxia led to colonic tissue damage, including epithelial cell shedding and inflammatory cell infiltration, and significantly reduced gut microbiota diversity in mice, manifested as a decreased Firmicutes/Bacteroidota ratio and increased abundances of Proteobacteria and Verrucomicrobiota. Fecal microbiota transplantation (FMT) improved colonic tissue morphology, reduced inflammatory cytokine levels, and enhanced intestinal barrier function. BQT intervention effectively alleviated colonic inflammation and reversed the down-regulation of tight junction proteins (ZO-1, Occludin, and Claudin-1) induced by hypoxia. In conclusion, gut microbiota dysbiosis is a key factor in high-altitude induced colonic inflammatory injury. FMT and BQT ameliorate high-altitude induced intestinal damage by restoring gut microbiota homeostasis and repairing the intestinal barrier. These findings suggest that supplementation with BQT may serve as a candidate microecological strategy for the prevention and treatment of intestinal injury in high-altitude populations.