Causal Effects between Gut Microbiome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Two-Sample Mendelian Randomization Study.

Background: Evidence from previous studies have implicated an important association between gut microbiota (GM) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), but whether there is a definite causal relationship between GM and ME/CFS has not been elucidated. Method: This study obtained instrumental variables of 211 GM taxa from the Genome Wide Association Study (GWAS), and mendelian randomization (MR) study was carried out to assess the effect of gut microbiota on ME/CFS risk from UK Biobank GWAS (2076 ME/CFS cases and 460,857 controls). Inverse variance weighted (IVW) was the primary method to analyze causality in this study, and a series of sensitivity analyses was performed to validate the robustness of the results. Results: The inverse variance weighted (IVW) method indicated that genus Paraprevotella (OR:1.001, 95%CI:1.000-1.003, value of p < 0.05) and Ruminococca- ceae_UCG_014 (OR 1.003, 95% CI 1.000 to 1.005, value of p < 0.05) were positively associated with ME/CFS risk. Results from the weighted median method supported genus Paraprevotella (OR 1.003, 95% CI 1.000 to 1.005, value of p < 0.05) as a risk factor for ME/CFS. Conclusion: This study reveals a causal relationship between genus paraprevotella, genus Ruminococcaceae_UCG_014 and ME/CFS, and our findings provide novel insights for further elucidating the developmental mechanisms mediated by the gut microbiota of ME/CFS.

Gut microbiota and Sjögren's syndrome: a two-sample Mendelian randomization study.

Background: The link between the gut microbiota (GM) and Sjögren's Syndrome (SS) is well-established and apparent. Whether GM is causally associated with SS is uncertain. Methods: The MiBioGen consortium's biggest available genome-wide association study (GWAS) meta-analysis (n=13,266) was used as the basis for a two-sample Mendelian randomization study (TSMR). The causal relationship between GM and SS was investigated using the inverse variance weighted, MR-Egger, weighted median, weighted model, MR-PRESSO, and simple model methods. In order to measure the heterogeneity of instrumental variables (IVs), Cochran's Q statistics were utilized. Results: The results showed that genus Fusicatenibacter (odds ratio (OR) = 1.418, 95% confidence interval (CI), 1.072-1.874, P = 0.0143) and genus Ruminiclostridium9 (OR = 1.677, 95% CI, 1.050-2.678, P = 0.0306) were positively correlated with the risk of SS and family Porphyromonadaceae (OR = 0.651, 95% CI, 0.427-0.994, P = 0.0466), genus Subdoligranulum (OR = 0.685, 95% CI, 0.497-0.945, P = 0.0211), genus Butyricicoccus (OR = 0.674, 95% CI, 0.470-0.967, P = 0.0319) and genus Lachnospiraceae (OR = 0.750, 95% CI, 0.585-0.961, P = 0.0229) were negatively correlated with SS risk using the inverse variance weighted (IVW) technique. Furthermore, four GM related genes: ARAP3, NMUR1, TEC and SIRPD were significant causally with SS after FDR correction (FDR<0.05). Conclusions: This study provides evidence for either positive or negative causal effects of GM composition and its related genes on SS risk. We want to provide novel approaches for continued GM and SS-related research and therapy by elucidating the genetic relationship between GM and SS.

No Causal Effects Detected in COVID-19 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Two Sample Mendelian Randomization Study.

New clinical observational studies suggest that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a sequela of COVID-19 infection, but whether there is an exact causal relationship between COVID-19 and ME/CFS remains to be verified. To investigate whether infection with COVID-19 actually causes ME/CFS, this paper obtained pooled data from the Genome Wide Association Study (GWAS) and analyzed the relationship between COVID susceptibility, hospitalization and severity of COVID and ME/CFS, respectively, using two-sample Mendelian randomization (TSMR). TSMR analysis was performed by inverse variance weighting (IVW), weighted median method, MR-Egger regression and weighted mode and simple mode methods, respectively, and then the causal relationship between COVID-19 and ME/CFS was further evaluated by odds ratio (OR). Eventually, we found that COVID-19 severity, hospitalization and susceptibility were all not significantly correlated with ME/CFS (OR:1.000,1.000,1.000; 95% CI:0.999-1.000, 0.999-1.001, 0.998-1.002; p = 0.333, 0.862, 0.998, respectively). We found the results to be reliable after sensitivity analysis. These results suggested that SARS-CoV-2 infection may not significantly contribute to the elevated risk of developing CFS, and therefore ME/CFS may not be a sequela of COVID-19, but may simply present with symptoms similar to those of CFS after COVID-19 infection, and thus should be judged and differentiated by physicians when diagnosing and treating the disease in clinical practice.

Fiscal Decentralization, Public Health Expenditure and Public Health-Evidence From China.

Since the beginning of the COVID-19 outbreak and the launch of the "Healthy China 2030" strategy in 2019, public health has become a relevant topic of discussion both within and outside China. The provision of public health services, which is determined by public health expenditure, is critical to the regional public health sector. Fiscal decentralization provides local governments with more financial freedom, which may result in changes to public health spending; thus, fiscal decentralization may influence public health at the regional level. In order to study the effects of fiscal decentralization on local public health expenditure and local public health levels, we applied a two-way fixed effect model as well as threshold regression and intermediate effect models to 2008-2019 panel data from China's 30 mainland provinces as well as from four municipalities and autonomous regions to study the effects of fiscal decentralization on public health. The study found that fiscal decentralization has a positive effect on increasing public health expenditure. Moreover, fiscal decentralization can promote improvements in regional public health by increasing public health expenditure and by improving the availability of regional medical public service resources. In addition, fiscal decentralization has a non-linear effect on public health.