AUTHOR=Bo Fuduo , Teng Hong , Shi Jianwei , Luo Zhengxiang , Xu Yang , Pan Ruihan , Xia Yan , Zhu Shuaishuai , Zhang Yansong , Zhang Wenbin 

TITLE=Exploring the causal relationship between gut microbiota and frailty: a two-sample mendelian randomization analysis

JOURNAL=Frontiers in Medicine

VOLUME=Volume 11 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1354037

DOI=10.3389/fmed.2024.1354037

ISSN=2296-858X

ABSTRACT=Background: Frailty is a complex geriatric syndrome that seriously affects the quality of life of older adults. In previous observational studies, frailty was strongly associated with the gut microbiota; however, further investigation is necessary to establish a causal link. To bridge this gap, we conducted a bidirectional Mendelian randomisation study to assess the causal relationship between frailty as measured by the frailty index, and gut microbiota composition.

Methods: Instrumental variables for the frailty index (N=175, 226) and 211 gut bacteria (N=18,340) were obtained through a genome-wide association study; a two-sample Mendelian randomisation was performed to assess whether gut microbiota is causally associated with frailty. In addition, we performed inverse Mendelian randomisation analyses to examine the direction of causality. Inverse variance weighting was used as the primary method in this study, supplemented by horizontal pleiotropy and sensitivity analyses to increase confidence in the results.

Results: Bacteroidia (b=-0.041, SE=0.017, P=0.014) and Eubacterium ruminantium (b=-0.027, SE=0.012, P=0.028) were protective against frailty amelioration. Additionally, five types of bacteria were associated with high frailty: Betaproteobacteria (b=0.049, SE=0.024, P=0.042), Bifidobacterium (b=0.042, SE=0.016, P=0.013), Clostridium innonocuum (b=0.023, SE=0.011, P=0.036), Eubacterium coprostanoligenes (b=0.054, SE=0.018, P=0.003), and Allisonella (b=0.032, SE=0.013, P=0.012). By contrast, frailty affected Butyrivibrio in the gut microbiota (b=1.225, SE=0.570, P=0.031). The results remained stable during sensitivity and validation analyses.

Conclusion: Our findings strengthen the evidence for a bidirectional causal link between the gut microbiota and frailty. A deeper understanding of this relationship is essential to optimally enhance the care of older adults and improve their quality of life.