Gut microbiota contributes to obstructive sleep apnea-induced hypertension by gut-heart axis in mice

Background

The gut microbiome has been closely linked to obstructive sleep apnea (OSA)-associated hypertension (HTN). However, its precise role in the pathogenesis of OSA-induced HTN remains unclear.

Methods

To clarify the causal relationship between gut dysbiosis and OSA-related HTN, C57BL6J mice were randomly assigned to four groups. Each group underwent fecal microbiota transplantation from healthy individuals (control), OSA patients (OSA group), OSA patients with pre-hypertension (OSA-pHTN group), or OSA patients with HTN (OSA-HTN group). The pro-hypertensive effects of the OSA gut microbiota were verified, and the composition and function of the gut microbiota were compared using 16S rDNA gene sequencing. Additionally, the gut microbiota-related lipopolysaccharide (LPS)/ Toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) pathway in aortic tissues was investigated.

Results

Fecal microbiota transplantation induced increased systolic blood pressure and aortic injury in mice from the OSA, OSA-pHTN and OSA-HTN groups, whereas no significant injury was observed in the control group. These three groups exhibited dysbiosis and impaired intestinal barrier function as evidenced by a reduction in Akkermansia and decreased expression of zonula occludens-1 and Occludin proteins. In addition, LPS, TLR4 and phosphorylated NF-κB expression were increased in aortic tissue from the three groups, and immunofluorescence showed a significant upregulation of TLR4 expression in aortic endothelial cells compared to controls.

Conclusion

This study demonstrates the pro-hypertensive effects of gut microbiota in OSA, mediated through the gut-derived LPS/TLR4/NF-κB pathway. These findings may guide the development of therapeutic strategies focused on restoring gut microbiome homeostasis.