Oropharyngeal microbiome alterations in sarcopenia: a nested case-control study in older adults

Sarcopenia, associated with systemic inflammation, respiratory diseases, and known gut dysbiosis, poses a significant health burden. However, the role of the nasopharyngeal and oropharyngeal (NP/OP) microbiome, a critical respiratory-digestive interface, in its pathogenesis remains unknown.

From a cohort of 830 nursing home residents with a sarcopenia prevalence of 61%, we conducted a nested case-control study. Sixty individuals with sarcopenia were propensity-score matched 1:1 with 60 non-sarcopenic controls (N = 120; 50% male). NP/OP swabs underwent full-length 16S rRNA gene sequencing to assess microbial composition and function.

Individuals with sarcopenia exhibited significantly lower OP microbial α-diversity (Shannon p = .016), which remained robust after multivariable adjustment (Shannon p < .05). NP diversity was unchanged. Sarcopenia was associated with an NP/OP microbial profile suggesting increased pro-inflammatory potential: enrichment of Moraxella (NP, linear discriminant analysis [LDA] > 2) and Haemophilus, Lactobacillus amylovorus, Listeriaceae (OP, LDA > 2), alongside depletion of potentially protective taxa (Pasteurellaceae, Alloprevotella tannerae, Prevotella aurantiaca, Eubacterium, Lachnoanaerobaculum) in controls. Specifically, increased Moraxella lincolnii (odds ratio [OR] = 1.068, p < .05) and decreased Eubacterium (OR = 0.968, p < .05) were associated with sarcopenia. Functionally, pathways related to lipopolysaccharide (LPS) biosynthesis and saturated fatty acid metabolism were upregulated in sarcopenia, while short-chain fatty acid (SCFA) and tryptophan metabolism were reduced.

Oropharyngeal microbial dysbiosis, characterized by lower diversity and a pro-inflammatory signature, is associated with sarcopenia. These findings highlight a potential relationship between the upper respiratory tract microbial environment and sarcopenia, a connection previously underappreciated. Understanding the interplay within the respiratory-gut-muscle axis may offer new perspectives on sarcopenia pathophysiology and its links with respiratory diseases.