Hypobaric hypoxia affects gut microbiota of rats through affected community assembly, reduced network resilience, and metabolic reprogramming.

In host-microbe interactions, host diet and environmental stress are key driving factors shaping the gut microbiota. Although previous studies have shown that hypoxia affects the structure and function of the gut microbiota in rodents, most have relied on 16S rRNA gene sequencing and lacked analysis of community assembly mechanisms, co-occurrence networks, and functional pathways. Here, we used metagenomic next-generation sequencing (mNGS) to examine the gut microbiota of rats exposed to hypobaric hypoxia (WH, simulated 6000 m altitude) compared to WL group (2100 m altitude). Hypoxia significantly altered β-diversity of gut microbiota, but did not affect its α-diversity. Community assembly was primarily governed by stochastic processes, with hypoxia stress reducing their impact. Microbial co-occurrence networks were dominated by positive correlations, although network resilience and stability declined under hypoxia. Helicobacter and Eubacterium were identified as high-abundance differentiating genera, and Akkermansia muciniphila was significantly enriched in WH group. Functional analysis revealed alterations in pathways related to protein synthesis and carbohydrate metabolism, suggesting that hypoxia may affect nutrient utilization by the host. Overall, these findings provide a comprehensive view of how hypoxic stress reshapes the gut microbiota of rats, offering new insights into microbial dynamics under environmental stress.