• Gabriel Baldanzi, Sergi Sayols-Baixeras, Jenny Theorell-Haglöw, Koen F Dekkers, Ulf Hammar, Diem Nguyen, Yi-Ting Lin, Shafqat Ahmad, Jacob Bak Holm, Henrik Bjørn Nielsen, Louise Brunkwall, Christian Benedict, Jonathan Cedernaes, Sanna Koskiniemi, Mia Phillipson, Lars Lind, Johan Sundström, Göran Bergström, Gunnar Engström, J Gustav Smith, Marju Orho-Melander, Johan Ärnlöv, Beatrice Kennedy, Eva Lindberg, and Tove Fall.
• Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
• Chest. 2023 Aug 1; 164 (2): 503516503-516.

BackgroundOSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism.Research QuestionDoes OSA in adults associate with the composition and functional potential of the human gut microbiota?Study Design And MethodsWe used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.ResultsWe found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.InterpretationOSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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