AUTHOR=Wang Zi , Han Shuai , Xiao Yinggang , Zhang Yang , Ge Yali , Liu Xin , Gao Ju 

TITLE=Genetically supported causality between gut microbiota and frailty: a two-sample Mendelian randomization study

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1324209

DOI=10.3389/fmicb.2024.1324209

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Background</title><p>A mounting body of evidence suggests a strong connection between gut microbiota and the risk of frailty. However, the question of causality remains unanswered. In this study, we employed a Mendelian randomization (MR) approach to assess potential causal relationships between gut microbiota and the risk of frailty.</p></sec><sec id="sec2"><title>Materials and methods</title><p>Summary statistics for the gut microbiome were obtained from a genome wide association study (GWAS) meta-analysis of the MiBioGen consortium (<italic>N</italic> = 18,340). Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (<italic>N</italic> = 175,226). Our primary analysis utilized the inverse variance weighted (IVW) method. To enhance the robustness of our results, we also applied weighted median methods, MR Egger regression, and MR pleiotropy residual sum and outlier test. Finally, we conducted reverse MR analysis to investigate the potential for reverse causality.</p></sec><sec id="sec3"><title>Results</title><p>IVW method identified 7 bacterial taxa nominally associated with the risk of FI. <italic>Class Bacteroidia</italic> (<italic>p</italic> = 0.033) and <italic>genus Eubacterium ruminantium</italic> group (<italic>p</italic> = 0.028) were protective against FI. In addition, <italic>class Betaproteobacteria</italic> (<italic>p</italic> = 0.042), <italic>genus Allisonella</italic> (<italic>p</italic> = 0.012), <italic>genus Bifidobacterium</italic> (<italic>p</italic> = 0.013), <italic>genus Clostridium innocuum group</italic> (<italic>p</italic> = 0.036) and <italic>genus Eubacterium coprostanoligenes group</italic> (<italic>p</italic> = 0.003) were associated with a higher risk of FI. No pleiotropy or heterogeneity were found.</p></sec><sec id="sec4"><title>Conclusion</title><p>The MR analysis indicates a causal relationship between specific gut microbiota and FI, offering new insights into the mechanisms underlying FI mediated by gut microbiota.</p></sec>