Abstract
Rationale Obstructive sleep apnea (OSA) is a chronic prevalent condition characterised by intermittent hypoxia (IH) and is associated with endothelial dysfunction and coronary artery disease (CAD). OSA can induce major changes in gut microbiome (GM) diversity and composition, which in turn may induce the emergence of OSA-associated morbidities. However, the causal effects of IH-induced GM changes on the vasculature remain unexplored.
Objectives To assess if vascular dysfunction induced by IH is mediated through GM changes.
Methods Fecal microbiota transplantation (FMT) was conducted on C57BL/6J naïve mice for 6 weeks to receive either IH or room air (RA) fecal slurry with or without probiotics (VSL3). In addition to 16S rRNA amplicon sequencing of their GM, FMT recipients underwent arterial blood pressure (aBP) and coronary artery and aorta function testing, and their trimethylamine N-oxide (TMAO) and plasma acetate levels were determined. Finally, C57BL/6J mice were exposed to IH, IH treated with VSL3, or RA for 6 weeks, and assessed aBP and coronary artery function.
Results GM taxonomic profiles correctly segregated IH from RA in FMT mice, and the normalising effect of probiotics emerged. Furthermore, IH-FMT mice exhibited increased aBP and TMAO levels, and impairments in aortic and coronary artery function (p<0.05) that were abrogated by probiotic administration. Lastly, Treatment with VSL3 under IH conditions did not attenuate elevations in aBP or CAD.
Conclusions Thus, GM alterations induced by chronic IH underlie, at least partially, the typical cardiovascular disturbances of sleep apnea, and can be mitigated by concurrent administration of probiotics.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: All authors declare no conflicts of interest.
- Received January 1, 2022.
- Accepted August 10, 2022.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
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