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Anaerobic pathogens associated with OSA may contribute to pathophysiology via amino-acid depletion

TitleAnaerobic pathogens associated with OSA may contribute to pathophysiology via amino-acid depletion
Publication TypePublication
AuthorsElgart M, Zhang Y, Zhang Y, Yu B, Kim Y, Zee PC, Gellman MD, Boerwinkle E, Daviglus ML, Cai J, Redline S, Burk RD, Kaplan R, Sofer T
Date Published2023 Dec
KeywordsAmino Acids, Anaerobiosis, Cohort Studies, Humans, Prospective Studies, Sleep Apnea, Obstructive

BACKGROUND: The human microbiome is linked to multiple metabolic disorders such as obesity and diabetes. Obstructive sleep apnoea (OSA) is a common sleep disorder with several metabolic risk factors. We investigated the associations between the gut microbiome composition and function, and measures of OSA severity in participants from a prospective community-based cohort study: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

METHODS: Bacterial-Wide Association Analysis (BWAS) of gut microbiome measured via metagenomics with OSA measures was performed adjusting for clinical, lifestyle and co-morbidities. This was followed by functional analysis of the OSA-enriched bacteria. We utilized additional metabolomic and transcriptomic associations to suggest possible mechanisms explaining the microbiome effects on OSA.

FINDINGS: Several uncommon anaerobic human pathogens were associated with OSA severity. These belong to the Lachnospira, Actinomyces, Kingella and Eubacterium genera. Functional analysis revealed enrichment in 49 processes including many anaerobic-related ones. Severe OSA was associated with the depletion of the amino acids glycine and glutamine in the blood, yet neither diet nor gene expression revealed any changes in the production or consumption of these amino acids.

INTERPRETATION: We show anaerobic bacterial communities to be a novel component of OSA pathophysiology. These are established in the oxygen-poor environments characteristic of OSA. We hypothesize that these bacteria deplete certain amino acids required for normal human homeostasis and muscle tone, contributing to OSA phenotypes. Future work should test this hypothesis as well as consider diagnostics via anaerobic bacteria detection and possible interventions via antibiotics and amino-acid supplementation.

FUNDING: Described in methods.

Alternate JournalEBioMedicine
PubMed ID38006744
PubMed Central IDPMC10709109
Grant ListHHSN268201300004C / HL / NHLBI NIH HHS / United States
R21 HL145425 / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
R01 HL161012 / HL / NHLBI NIH HHS / United States
R35 HL135818 / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
HHSN268201300003C / HG / NHGRI NIH HHS / United States
Manuscript Lead/Corresponding Author Affiliation: 
HCHS/SOL Baseline Visit - Sleep Center - Harvard Medical School/The Brigham & Women's Hospital
Manuscript Status: