Abstract: Objective　To explore the mechanism of gut microbiota in intestinal damage in high-altitude hypoxic environment.     Methods    Twenty C57BL/6 mice were randomly divided into a control group and an exposure group according to the ratio of 1:1. After the successful modeling of the 6000-meter high-altitude hypoxia model, the feces, blood and proximal colon tissue of these two groups were collected. The structure of gut microbiota in feces was determined by 16S rDNA analysis. The blood biochemical indexes were detected. The pathological changes of intestinal mucosal structure were observed by HE and PAS staining. The mRNA expression levels of ZO-1, Occludin, IL-6 and TNFα of colon tissue were measured by RT-qPCR.    Results    Compared with the control group, the red blood cell, hemoglobin and hematocrit values of the exposure group significantly increased. The high-altitude hypoxia model was successfully established. The 16S rDNA showed that the gut microbiota was disordered and the diversity declined, the content of the mucin-degrading bacteria Akkermansia and pathogenic bacterias Clostridium XVIII, Prevotella increased, the relative content of the short-chain fatty acids producing bacteria Roseburia, Odoribacter, Lachnospiracea, Butyricicoccus and Olsenella decreased. HE and PAS staining results showed that the interruption of colon epithelial continuity, atrophy of glands, shortening of crypts and reduction of goblet cells, which indicated the damage of intestinal structure and mucosal barrier. The expression levels of tight junction protein Occludin and ZO-1 mRNA decreased, which confirmed the disruption of intestinal mucosal of the exposure group. The expression level of inflammatory factors IL-6 and TNFα increased, which may be related to intestinal inflammatory reaction.   Conclusions   The intestinal damage caused by high-altitude hypoxic environment may be related to the change of gut microbiota. Gut microbiota disorder and diversity decreased, the relative abundance of pathogenic bacteria increased and probiotics decreased. These alterations cause the intestinal mucosal damage, intestinal inflammation, intestinal damage, and finally lead to high-altitude intestinal related diseases.

Key words: High-altitude hypoxia, 　Gut microbiota, 　Intestinal damage, 　Intestinal mucosal barrier