Changes in the Gut Microbiota of Rats in High-Altitude Hypoxic Environments

Abstract

This study was conducted to investigate the effects of high-altitude hypoxic environments on the gut microbiota. Male Sprague-Dawley rats were randomly divided into three groups, namely, the plain, moderate-altitude hypoxic, and high-altitude hypoxic groups. On the 3rd, 7th, 15th, and 30th days of exposure, fecal samples were collected and analyzed via 16S rRNA gene sequencing technology. Fecal microbiota transplantation (FMT) experiments were also performed. The results showed significant differences between the gut microbiota structure and diversity of rats in the high-altitude hypoxic group and those of rats in the other groups. Further, compared with that of rats in the plain group, the gut microbiota of rats in the two hypoxic groups showed the most significant changes on day 7. Furthermore, the gut microbiota of the rats in the FMT groups exhibited changes and became increasingly similar to those of the rats in the hypoxic groups. We also identified the phylum Firmicutes, genus Akkermansia, and genus Lactobacillus as the core microbiota under hypoxic conditions. Phenotypic analysis indicated a decrease in the proportion of aerobic bacteria and an increase in that of anaerobic bacteria, possibly owing to the high-altitude hypoxic environment. Additionally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including carbohydrate metabolism, energy metabolism, glycan biosynthesis, and metabolism. These findings indicated significant changes in gut microbiota structure and diversity under high-altitude hypoxia, establishing a foundation for further research on the pathogenesis and development of diseases, as well as drug metabolism, under high-altitude hypoxia. IMPORTANCE In this study, we investigated the effects of high-altitude hypoxic environments with low oxygen levels on the gut microbiota characteristics of rats. We observed that high-altitude hypoxia is an important environmental factor that can affect gut microbiota structure and diversity, thereby affecting homeostasis in the host intestinal environment. These findings provide a basis for further studies on disease initiation and development, as well as drug metabolism, in high-altitude hypoxic environments.

Keywords: 16S rRNA gene; diversity; fecal microbiota transplantation; gut microbiota; high-altitude hypoxia; structure.

FIG 1

Diversity analysis of gut microbiota of rats. (A) Dilution curve of Good’s coverage; (B) Pielou index; (C) Shannon index; (D) principal-coordinate analysis with weighted UniFrac distance; (E) ANOSIM for weighted UniFrac. P, plain group; M3, M7, M15, and M30, 3rd, 7th, 15th, and 30th days of the moderate-altitude hypoxic group; H3, H7, H15, and H30, 3rd, 7th, 15th, and 30th days of the high-altitude hypoxic group. Means with same box followed by different superscript letters differ at a P value of <0.05.

FIG 2

Histogram of community structure of gut microbiota in rats at the phylum and genus levels. (A) Phylum level; (B) genus level.

FIG 3

Analysis of differences in the microbiota among different altitudes.

FIG 4

Analysis of differences in the microbiota among different high-hypoxic altitude treatment times. (A) Moderate-altitude hypoxic groups; (B) high-altitude hypoxic groups.

FIG 5

Functional analysis of the gut microbiota in each group of rats. (A) BugBase functional analysis; (B) Tax4Fun functional prediction analysis.

FIG 6

Histogram of community structure of gut microbiota in rats at the phylum and genus levels. (A) Phylum level; (B) genus level. FMT-P, normal rats receiving autoclaved saline; FMT-MH, normal rats receiving fecal suspension from the 7th-day moderate-altitude hypoxic donor rats; FMT-HH, normal rats receiving fecal suspension from the 7th-day high-altitude hypoxic donor rats.

FIG 7

FMT-related associations with gut microbial changes. (A) Phylum level; (B) genus level; (C) principal-coordinate analysis with weighted UniFrac distance.