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 meters of elevation for 14 days. The mice carrying the myeloid Hif-1β deletion displayed aggravated hypoxic phenotypes, significantly greater weight loss, and significantly higher cardiac index values compared with the wild-type group. The levels of some cytokines increased under 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 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 only found in wild-type mice 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 reveals genetic and microecological pathways for research on mechanisms of hypoxia.

Hypoxia: The “Invisible Pusher” of Gut Microbiota

“…During environmental hypoxia in mice, the Bacteroidetes abundance increased at both the family and genus levels from days 1 to 14 in mice with hypoxia inducible factor-1 (HIF-1) deficiency in their bone marrow cells. This difference was significant compared with that of the wild-type group ( Han N. et al, 2020 ) and was consistent with previous findings that Bacteroidetes was more abundant in HIF-1-deficient mice than in wild-type mice ( Sun et al, 2020 ).…”

Identification and cross-validation of autophagy-related genes in cardioembolic stroke

“…In humans, the levels of HIF-1 transcripts are directly correlated with those of hypothalamic transcripts for proteins involved in inflammation, regulation of apoptosis, autophagy, and the ubiquitin/proteasome system; in mice with high fat diet, diet-induced obesity was accompanied by increased HIF-1 expression ( 52 ). Moreover, mice carrying the myeloid HIF-1β deletion displayed aggravated hypoxic phenotypes and significantly greater weight loss and significantly higher cardiac index values than the wild-type group ( 53 ). Considering that platelet thrombus formation is usually positively correlated with hyperlipidemia, the increase of HIF-1β might indicate the accumulated inflammation and the disorder of lipid metabolism in CE stroke.…”

HIF‐1α targeted deletion in myeloid cells decreases MDSC accumulation and alters microbiome in neonatal mice

“…As mentioned before, we are not aware of other studies investigating an impact of MDSC on intestinal microbiome composition. However, it has been shown that a myeloid knockout of HIF‐1β leads to altered microbiome composition in mice exposed to hypoxia [59]. Conversely, metabolites produced by the intestinal microbiome were shown to influence the expression of HIF‐1α; for example, short chain fatty acids (SCFA) cause HIF‐α stabilization by inhibition of prolylhydroxylases (PHDs) [60].…”