Effects of Myeloid Hif-1β Deletion on the Intestinal Microbiota in Mice under Environmental Hypoxia

Abstract

External environmental factors can cause an imbalance in intestinal flora. For people living in the extremes of a plateau climate, lack of oxygen is a primary health challenge that leads to a series of reactions. We wondered how intestinal microorganisms might change in a simulated plateau environment and what changes might occur in the host organism and intestinal microorganisms in the absence of hypoxia-related factors. In this study, mice carrying a knockout of hypoxia-inducible factor 1β (Hif-1β) in myeloid cells and wild-type mice were raised in a composite hypoxic chamber to simulate a plateau environment at 5,000 m of elevation for 14 days. The mice carrying the myeloid Hif-1β deletion displayed aggravated hypoxic phenotypes in comparison to and significantly greater weight loss and significantly higher cardiac index values than the wild-type group. The levels of some cytokines increased in the hypoxic environment. Analysis of 16S rRNA sequencing results showed that hypoxia had a significant effect on the gut microbiota in both wild-type and Hif-1β-deficient mice, especially on the first day. The levels of members of the Bacteroidaceae family increased continuously from day 1 to day 14 in Hif-1β deletion mice, and they represented an obviously different group of bacteria at day 14 compared with the wild-type mice. Butyrate-producing bacteria, such as Butyricicoccus, were found in wild-type mice only after 14 days in the hypoxic environment. In conclusion, hypoxia caused heart enlargement, greater weight loss, and obvious microbial imbalance in myeloid Hif-1β-deficient mice. This study revealed genetic and microecological pathways for research on mechanisms of hypoxia.

Keywords: Hif-1β; gut microbiota; hypoxia; imbalance; myeloid cell.