Gut microbiota changes associated with frailty in older adults: A systematic review of observational studies

Background: Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes, including falls, disability, incapacity and death. While an increasing number of studies suggest that the gut microbiota may play a key role in the pathophysiology of frailty, direct evaluation of the association between gut microbiome alterations and frailty in older adults remains limited.

Aim: To gain insight into gut dysbiosis in frail older adults.

Methods: Seven electronic databases (China National Knowledge Infrastructure, VIP, SinoMed, Wanfang, PubMed, Web of Science and EMBASE) were searched for articles published before October 31, 2023 to identify observational studies that compared the microbiomes of older adults with and without frailty. The diversity and composition of the gut microbiota were the main outcomes used to analyze the associations of changes in the gut microbiota with frailty in older adults. The quality of the included studies was assessed via the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality.

Results: Eleven observational studies with 912 older adults were included in this review. Consistent results revealed a significant difference in the gut microbiota composition between frail and non-frail older adults, with a significant decrease in α diversity and a significant increase in β diversity in frail older adults. The pooled results revealed that at the phylum level, four microbiota (Actinobacteria, Proteobacteria, Verrucomicrobia and Synergistetes) were significantly enriched, and two microbiota (Firmicutes and Fusobacteria) were significantly depleted in frail older adults. At the family level, the results consistently revealed that the abundances of 6 families, most of which belong to the Actinobacteria or Proteobacteria phylum, were greater in frail than in non-frail older adults. At the genus or species level, consistent results from more than two studies revealed that the abundances of the genera Prevotella, Faecalibacterium, and Roseburia were significantly lower in frail older adults; individual studies revealed that the abundances of some genera or species (e.g., Megamonas, Blautia, and Megasphaera) were significantly lower, whereas those of other genera or species (e.g., Bifidobacterium, Oscillospira, Ruminococcus and Pyramidobacter) were significantly greater in frail older adults.

Conclusion: This systematic review suggests that changes in the gut microbiota are associated with frailty in older adults, which is commonly reflected by a reduction in beneficial species and an increase in pathogenic species. However, further studies are needed to confirm these findings.