Background Observational studies have indicated a potential link between gut microbiota and sarcopenia. However, the underlying mechanisms and a causal relationship have not been established. Thus, the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits, including low hand grip strength and appendicular lean mass (ALM), to shed light on the gut-muscle axis. Methods To investigate the potential impact of gut microbiota on low hand grip strength and ALM, we utilized a two-sample Mendelian randomization (MR) approach. Summary statistics were obtained from genome-wide association studies of gut microbiota, low hand grip strength, and ALM. The primary MR analysis employed the random-effects inverse-variance weighted (IVW) method. To assess the robustness, we conducted sensitivity analyses using the MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) test to detect and correct for horizontal pleiotropy, as well as the MR-Egger intercept test and leave-one-out analysis. Results Alcaligenaceae, Family XIII, and Paraprevotella were positively associated with the risk of low hand grip strength (P-values < 0.05). Streptococcaceae were negatively associated with low hand grip strength (P-values < 0.05). Eight bacterial taxa (Actinomycetales, Actinomycetaceae, Bacteroidaceae, Porphyromonadaceae, Prevotellaceae, Bacteroides, Marvinbryantia, and Phascolarctobacterium) were associated with a higher risk of ALM (P-values < 0.05). Eubacterium fissicatena group was negatively associated with ALM (P-values < 0.05). Conclusion We found several gut microbiota components causally associated with sarcopenia-related traits. Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota, contributing to a better understanding of the gut-muscle axis.

Background: Alzheimer's disease (AD) has become a common illness affecting the elderly, adding to society's social and financial burden. We used two-sample Mendelian randomization (MR) in this study to determine the association between working status and AD. Methods:We performed a two-sample MR analysis. The genetic associations were derived from the UK Biobank (n = 263,615) and the International Genomics of Alzheimer's Project (n = 63,926). Inverse variance weighted (IVW), MR-Egger, and weighted median were used in the MR analysis. The funnel plot, Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were used in sensitivity analyses.Further risk factor analyses were carried out to look into the potential mediators.Results: Jobs involve heavy manual or physical work (OR = 2.13, 95%CI 1.36-3.36; p = .0011), job involves mainly walking or standing (OR = 1.74, 95%CI 1.19-2.54; p = .004), and job involves shift work (OR = 2.78, 95%CI 1.14-6.80; p = .02) increased the risk of AD in the IVW analysis. There was no heterogeneity and no horizontal pleiotropy in the sensitivity analysis. Risk factor analysis suggested that each of the above association may be mediated by different risk factors. Conclusion:Our study adds to the evidence that the development of AD is associated with the working status (job involves heavy manual or physical work, job involves mainly walking or standing, and job involves shift work) by using extensive human genetic data.

Background Epidemiological evidence relating sleep disorders to end-stage renal disease (ESRD) has been obscure. The present study is sought to examine the association between sleep traits and ESRD. Methods For this analysis, we selected genetic instruments for sleep traits from published genome-wide association studies (GWAS). As instrumental variables, independent genetic variations linked with seven sleep-related features (sleep duration, getting up in the morning, daytime napping, chronotype of morning/evening person, sleeplessness/insomnia, non-snoring, and daytime dozing) were chosen. A two-sample Mendelian randomization (TSMR) study was conducted to assess the causal relationship between sleep traits and ESRD (N = 33,061). The reverse MR analysis subsequently determined the causal relationship between ESRD and sleep traits. The causal effects were estimated using inverse variance weighted, MR-Egger, weighted median. To conduct sensitivity studies, Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plot were used. To study the potential mediators, multivariable mendelian randomization analyses were undertaken further. Results Genetically predicted sleeplessness/ insomnia (OR = 6.11, 95%CI 1.00-37.3, P = 0.049, FDR = 0.105), getting up in the morning easily(OR = 0.23, 95%CI 0.063–0.85; P = 0.0278, FDR = 0.105), non-snoring (OR = 4.76E-02, 95%CI 2.29E-03-0.985, P = 0.0488, FDR = 0.105) was suggestively associated with the risk of ESRD. However, we found no evidence favoring a causal association between other sleep traits and ESRD through the IVW method. Conclusion The present TSMR found no strong evidence of a bidirectional causal association between genetically predicted sleep traits and ESRD.

Inflammatory bowel disease (IBD) has been reported to be associated with hepatobiliary diseases. Previous observational and Mendelian randomization (MR) studies have suggested a causal association between IBD and primary sclerosing cholangitis (PSC). However, it is unclear whether IBD has a causal association with primary biliary cholangitis (PBC): another autoimmune liver disease. We obtained genome-wide association study (GWAS) statistics from published GWASs for PBC, UC, and CD. We screened qualified instrumental variables (IVs) based on the three major assumptions of MR. To determine the causal relationships between UC or CD and PBC, two-sample MR analyses were performed using inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) methods, and sensitivity analyses were conducted to validate the robustness of the results. We also conducted reverse MR analysis to reveal the causal association between PBC and UC or CD. UC was associated with a higher risk of PBC (OR 1.35, 95% CI 1.05–1.73, P = 0.02) in the IVW method, and CD was associated with an increased risk of PBC (OR 1.18, 95% CI 1.03–1.36, P = 0.02) in IVW. The weighted median and MR-Egger regression of both diseases showed a consistent direction but were not statistically significant. Results of the reverse MR analysis did not suggest genetic susceptibility that PBC was associated with an increased risk of UC (OR 1.05, 95% CI 0.95–1.17, P = 0.34) or CD (OR 1.1, 95% CI 0.99–1.20, P = 0.06). The present study revealed that IBD subtypes could increase the incidence of PBC, but in turn, PBC did not increase the incidence of IBD subtypes. Understanding that IBD and PBC constitute mutual risk factors can help with the clinical management of both diseases.

Background Inflammatory bowel disease (IBD) was reported to be associated with hepatobiliary disease. Previous observational and Mendelian randomization (MR) studies suggested a causal association between IBD and primary sclerosing cholangitis (PSC). However, it is unclear whether IBD has causal association with primary biliary cholangitis (PBC): another autoimmune liver disease. Methods We obtained genome-wide association study (GWAS) statistics from published GWASs for PBC, UC and CD. We screened qualified instrumental variables (IVs) based on the three major assumptions of MR. To determine the causal relationship between UC or CD and PBC, two-sample MR analyses were performed using inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods, and sensitivity analyses were conducted to validate the robustness of the results. We also conducted reverse MR analysis to reveal the causal association between PBC and UC or CD. Results UC were associated with a higher risk of PBC (OR = 1.35, 95% CI: 1.05–1.73, P = 0.02) in IVW method. And CD was associated with an increased risk of PBC (OR = 1.18, 95% CI: 1.03–1.36, P = 0.02) in IVW method. The weighted median and MR-Egger regression of both diseases showed a consistent direction but not statistically significant. Results of reverse MR analysis did not suggest genetic susceptibility to psoriasis was associated with increased risk of UC (OR = 1.05, 95% CI: 0.95–1.17, P = 0.34) or CD (OR = 1.1, 95% CI: 0.99–1.20, P = 0.06). Conclusion The present study revealed that IBD subtypes could increase the incidence of PBC, but in turn PBC did not increase the incidence of IBD subtypes. Understanding that IBD and PBC constitute mutual risk factors can help with clinical management of both diseases.