Alterations in gut microbiota and their associations with cardiac injury in rats after exposure to continuous normobaric hypoxia

Abstract:

[Objective] To investigate the alterations in gut microbiota and their associations with the biomarkers of myocardial hypertrophy induced by continuous normobaric hypoxia in rats. [Methods] Sixteen specific-pathogen-free female Sprague-Dawley rats were randomly assigned into two groups: the normoxia group and the hypoxia group. After adaptation for 1 week, the rats in the hypoxia group were immediately placed into the hypoxic chamber with the oxygen concentration at 10% for 30 d, and the rats without hypoxia treatment were set as the control. We monitored the body weight of each rat daily, determined the haematological and biochemical parameters as well as the organ coefficients at the end of the experiments. Further, we collected stools from each rat before (day 0) and after hypoxia challenge (day 30) to test the gut microbiota by using 16S rRNA gene sequencing. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the mRNA levels of gene ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide), Myh6 (myosin heavy chain 6), and Myh7 (myosin heavy chain 7), the biomarkers of myocardial hypertrophy in the right ventricular tissue. Spearman correlation analysis was performed to explore the links between intestinal microbiomes and parameters. [Results] Hypoxia reduced the body weight, increased the erythrocyte count, hemoglobin level, and hematocrit, and failed to affect the counts of leukocytes and platelets. Hypoxia increased the right ventricular index, enhanced the activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in the serum, and up-regulated the mRNA levels of BNP and Myh7 in right ventricular tissue, which suggested pathologically myocardial hypertrophy after hypoxia challenge for 30 d. Hypoxia significantly altered the alpha diversity and beta diversity of gut microbiota in rats. The results of linear discriminant analysis effect size (LEfSe) showed that the rats exposed to hypoxia had lower relative abundance of Prevotellaceae and Lachnospiraceae and higher relative abundance of Lactobacilliaceae and Lactobacillus than the control rats. LDH was positively correlated with Monoglobus and Papilibacter and negatively correlated with Defluvialeaceae_UCG-011. CK was positively correlated with strain RF39. The expression of BNP was positively correlated with Ruminocochaceae_UCG_009, and that of Myh6 was positively correlated with Prevotellaceae_NK3B31_group and Helicobacter.[Conclusion] The species richness, evenness, and composition of gut microbiota in rats are greatly affected after exposure to continuous normobaric hypoxia. The changes of gut microbiota have correlations with the biomarkers of myocardial hypertrophy induced by hypoxia, indicating that gut microbiota plays a crucial role in hypoxia-induced myocardial hypertrophy.