This study identified distinct microbial and functional signatures associated with frailty syndrome in older adults, with Eggerthella, Parabacteroides, and Erysipelatoclostridium enriched in frail individuals and Christensenellaceae R-7 group, Erysipelotrichaceae UCG-003, and Hungatella enriched in non-frail individuals, highlighting the complex interplay between gut microbiota and host physiology in aging.
Key Findings
Results
Eggerthella, Parabacteroides, and Erysipelatoclostridium were significantly more abundant in frailty syndrome individuals, while Christensenellaceae R-7 group, Erysipelotrichaceae UCG-003, and Hungatella were enriched in non-frail individuals.
Analysis was based on 16S rRNA gene sequencing of fecal samples from 203 older adults (FS: n=64, NFS: n=139).
These consistent taxonomic patterns were observed when comparing frailty syndrome versus non-frailty syndrome groups.
The Christensenellaceae R-7 group was also associated with better mobility in addition to being enriched in non-frail individuals.
Results
Metagenomics analysis identified 680 KEGG functions differing between frailty syndrome and non-frailty syndrome groups, categorized into 28 metabolic pathways.
Frailty syndrome individuals had overrepresented biotin metabolism, antimicrobial resistance, and energy production pathways.
Frailty syndrome individuals had underrepresented ribosomal and protein synthesis and sporulation pathways.
Both 16S rRNA gene and metagenomics sequencing were used for functional analysis.
Results
Resistome analysis identified the tetM/tetO (K18220) gene as the most abundant antimicrobial resistance gene, with tetracycline, β-lactam, and macrolide resistance primarily mediated by antibiotic efflux and transporters.
Antimicrobial resistance pathways were overrepresented in frailty syndrome individuals.
Resistance mechanisms were primarily mediated by antibiotic efflux and transporters.
Three major classes of antibiotic resistance were identified: tetracycline, β-lactam, and macrolide.
Results
Age and diabetes acted as confounding factors in frailty syndrome for both 16S rRNA gene and metagenomics sequencing analyses after adjusting for covariates.
Covariates were adjusted for in the analysis of gut microbiota differences between frailty syndrome and non-frailty syndrome groups.
Both age and diabetes were identified as confounding factors in the relationship between gut microbiota and frailty syndrome.
This confounding effect was consistent across both 16S rRNA gene sequencing and metagenomics sequencing approaches.
Methods
The study analyzed the role of gut microbiota in frailty syndrome and related comorbidities including sarcopenia, impaired lower extremity function, and anthropometric variables.
A total of 203 older adults were included: 64 with frailty syndrome and 139 non-frailty syndrome participants.
Both 16S rRNA gene sequencing and metagenomics sequencing of fecal samples were employed.
Associated comorbidities assessed included sarcopenia, impaired lower extremity function (ILEF), and anthropometric variables.
The Christensenellaceae R-7 group was specifically associated with better mobility, linking microbiota composition to lower extremity function.
Barberá A, Ortolá R, Sotos-Prieto M, Rodríguez-Artalejo F, Moya A, Ruiz-Ruiz S. (2026). The Role of the Gut Microbiome in the Complex Network of Frailty Syndrome and Associated Comorbidities in Aging.. Aging cell. https://doi.org/10.1111/acel.70365