Interactive Effect of Combined Intermittent and Sustained Hypoxia and High-Fat Diet on the Colonic Mucosal Microbiome and Host Gene Expression in Mice

Abstract

Purpose Gut dysbiosis can cause cardiometabolic disease. Gut dysbiosis can be independently caused by high-fat diet (HFD) and intermittent hypoxia (IH; characterizing obstructive sleep apnea), but the interactive effect of combined intermittent and sustained hypoxia (IH+SH) (characterizing obesity hypoventilation syndrome) and HFD on gut dysbiosis is unclear. We aimed to investigate the interactive effect of a combination of IH and SH and HFD on proximal colonic microbiota and colonic gene expression pattern. Methods Male mice (n=16) were randomly received four different combinations of diet (normal versus HFD) and oxygen conditions (normoxia versus IH+SH) for 4 weeks. Bacterial DNA and mucosal epithelial cell RNA from proximal colon were collected for analysis of adherent microbiome and host’s gene expression analysis. Results HFD during IH+SH (22.6 ± 5.73; SD) led to greater Firmicutes: Bacteroidetes ratio than HFD during normoxia (5.89 ± 1.19; p=0.029). HFD significantly decreased microbial diversity as compared to normal diet, but the addition of IH+SH to HFD mildly reversed such effects. When compared to HFD during normoxia, HFD with combination of IH+SH resulted in changes to host mucosal gene expression for apical junctional complexes and adhesion molecules. Specifically, when compared to HFD during normoxia, HFD during IH+SH led to upregulation of Claudin 2 and Syk (tight junction dysfunction and increased mucosal permeability), while the barrier promoting claudin 4 was downregulated. Conclusion HFD during combined IH and SH causes greater gut dysbiosis and potentially adverse changes in colonic epithelial transcriptome than HFD during normoxia. The latter changes are suggestive of impaired gut barrier function.

Lack of associations between thyroid dysfunction and obstructive sleep apnea-hypopnea syndrome: A meta-analysis

“…Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a prevalent sleep disorder marked by recurrent, partial, or complete episodes of breathing pauses owing to an obstruction of the upper airway during sleep, thereby causing intermittent low blood oxygen saturation. [ 1 , 2 ] Globally, there are close to one billion individuals with OSAHS, with China having the highest number, followed by the United States, Brazil, and other countries. [ 3 ] Recent data depict the prevalence of moderate to severe OSAHS as 49.7% in males and 23.4% in females, with an apnea-hypopnea index (AHI) of 15 events every hour as the standard.…”