Abstract
Background Obstructive sleep apnoea (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 diversity and composition, which in turn may induce the emergence of OSA-associated morbidities. However, the causal effects of IH-induced gut microbiome changes on the vasculature remain unexplored. Our objective was to assess if vascular dysfunction induced by IH is mediated through gut microbiome changes.
Methods Faecal microbiota transplantation (FMT) was conducted on C57BL/6J naïve mice for 6 weeks to receive either IH or room air (RA) faecal slurry with or without probiotics (VSL#3). In addition to 16S rRNA amplicon sequencing of their gut microbiome, FMT recipients underwent arterial blood pressure 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 VSL#3 or RA for 6 weeks, and arterial blood pressure and coronary artery function assessed.
Results Gut microbiome taxonomic profiles correctly segregated IH from RA in FMT mice and the normalising effect of probiotics emerged. Furthermore, IH-FMT mice exhibited increased arterial blood pressure and TMAO levels, and impairments in aortic and coronary artery function (p<0.05) that were abrogated by probiotic administration. Lastly, treatment with VSL#3 under IH conditions did not attenuate elevations in arterial blood pressure or CAD.
Conclusions Gut microbiome alterations induced by chronic IH underlie, at least partially, the typical cardiovascular disturbances of sleep apnoea and can be mitigated by concurrent administration of probiotics.
Abstract
Intermittent hypoxia-induced gut microbiome alterations elicit cardiovascular disturbances such as hypertension and coronary artery dysfunction that are prevented by probiotic administration https://bit.ly/3KkYzIt
Footnotes
Data availability: Custom scripts used to analyse 16S rRNA amplicon sequencing data are available at https://github.com/ericsson-lab/IH_RA_FMT. All sequencing data have been uploaded to the NCBI Sequence Read Archive (SRA) with SRA BioProject accession number PRJNA888956.
This article has an editorial commentary: https://doi.org/10.1183/13993003.01974-2022
Author contributions: M. Badran, A. Khalyfa, S.B. Bender and A.C. Ericsson performed experiments. M. Badran and A.C. Ericsson analysed data. M. Badran wrote the manuscript. D. Gozal provided the conceptual framework and continuous guidance for the project, and critically reviewed and revised the manuscript. All authors reviewed and approved the contents of the manuscript.
Conflict of interest: All authors declare no conflicts of interest.
Support statement: This study was supported in part by NIH grants HL130984, HL140548 and G061824, and by a Tier 2 Grant from the University of Missouri. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received January 1, 2022.
- Accepted August 10, 2022.
- Copyright ©The authors 2023. For reproduction rights and permissions contact permissions{at}ersnet.org