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=11

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=<sec id="sec1"><title>Background</title><p>Frailty is a complex geriatric syndrome that seriously affects the quality of life of older adults. Previous observational studies have reported a strong relationship of frailty with the gut microbiota; however, further studies are warranted to establish a causal link. Accordingly, we aimed to conduct a bidirectional Mendelian randomization study to assess the causal relationship between frailty, as measured by the frailty index, and gut microbiota composition.</p></sec><sec id="sec2"><title>Methods</title><p>Instrumental variables for the frailty index (<italic>N</italic> = 175, 226) and 211 gut bacteria (<italic>N</italic> = 18,340) were obtained through a genome-wide association study. A two-sample Mendelian randomization analysis was performed to assess the causal relationship of gut microbiota with frailty. Additionally, we performed inverse Mendelian randomization analyses to examine the direction of causality. Inverse variance weighting was used as the primary method in this study, which was supplemented by horizontal pleiotropy and sensitivity analyses to increase confidence in the results.</p></sec><sec id="sec3"><title>Results</title><p><italic>Bacteroidia</italic> (<italic>b</italic> = −0.041, SE = 0.017, <italic>p</italic> = 0.014) and <italic>Eubacterium ruminantium</italic> (<italic>b</italic> = −0.027, SE = 0.012, <italic>p</italic> = 0.028) were protective against frailty amelioration. Additionally, the following five bacteria types were associated with high frailty: <italic>Betaproteobacteria</italic> (<italic>b</italic> = 0.049, SE = 0.024, <italic>p</italic> = 0.042), <italic>Bifidobacterium</italic> (<italic>b</italic> = 0.042, SE = 0.016, <italic>p</italic> = 0.013), <italic>Clostridium innocuum</italic> (<italic>b</italic> = 0.023, SE = 0.011, <italic>p</italic> = 0.036), <italic>E. coprostanoligenes</italic> (<italic>b</italic> = 0.054, SE = 0.018, <italic>p</italic> = 0.003), and <italic>Allisonella</italic> (<italic>b</italic> = 0.032, SE = 0.013, <italic>p</italic> = 0.012). Contrastingly, frailty affected <italic>Butyrivibrio</italic> in the gut microbiota (<italic>b</italic> = 1.225, SE = 0.570, <italic>p</italic> = 0.031). The results remained stable within sensitivity and validation analyses.</p></sec><sec id="sec4"><title>Conclusion</title><p>Our findings strengthen the evidence of a bidirectional causal link between the gut microbiota and frailty. It is important to elucidate this relationship to optimally enhance the care of older adults and improve their quality of life.</p></sec>