Accumulating evidence indicates that gut microbiota closely correlates with the tumorigenesis of digestive system cancers (DSCs). However, whether the causality between gut microbiota and DSCs exists is unknown. Genome-wide association study (GWAS) summary statistics for gut microbiota and DSCs and the bidirectional two-sample Mendelian randomization (MR) analysis were utilized to assess the causality between gut microbiota and DSCs. Sensitivity analyses were performed to evaluate the robustness of our results. We found that the genus Eggerthella (OR = 0.464, 95%CI: 0.27 to 0.796, p = 0.005) was negatively associated with the risk of gastric cancer. The genetically predicted genus Lachnospiraceae FCS020 group (OR = 0.607, 95%CI: 0.439 to 0.84, p = 0.003) correlated with a lower risk of colorectal cancer, and genus Turicibacter (OR = 0.271, 95%CI: 0.109 to 0.676, p = 0.005) was a protective factor for liver cancer. In the reverse MR, DSCs regulated the relative abundance of specific strains of gut microbiota. We comprehensively screened the association between gut microbiota and DSCs using a bidirectional two-sample MR analysis and identified the causality between several microbial taxa and DSCs. Our discoveries are beneficial for the development of novel microbial markers and microbiota-modifying therapeutics for DSC patients.

Several observational studies have indicated the potential associations among calcium, vitamin D (Vit-D), and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subject to residual confounding factors and reverse causation. Therefore, we aimed to explore the bidirectional causal effects among serum calcium, Vit-D, PTH, and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis of the datasets from IEU OpenGWAS database. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratios (ORs) with their 95% confidence intervals (CIs). The results of the inverse variance weighted method did not reveal any causal relationship between the genetically predisposed calcium (OR = 0.92, 95% CI: 0.80–1.06, p = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83–1.19, p = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a decreased level of PTH (beta: −0.19, 95%CI: −0.34 to −0.04, p = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms via which IBS affects serum PTH need to be further investigated.

Background: Previous studies indicate that gut microbiota correlates to primary sclerosing cholangitis (PSC), but the causation is still unclear. We sought to reveal the causal relationship between gut microbiota and PSC with a bidirectional two-sample Mendelian randomization (MR) analysis. Methods: The large-scale genome-wide association study (GWAS) summary statistics and a bidirectional two-sample MR study were used to assess the causality between gut microbiota and PSC. Multiple sensitivity analyses were used to identify the robustness of our results. Results: Three microbial taxa causally correlated to PSC. Genus Ruminococcaceae UCG002 (OR: 1.855, 95% CI: 1.068–3.220, P = 0.028) increased the risk of PSC. Class Betaproteobacteria (OR: 0.360, 95% CI: 0.171–0.758, P = 0.007), and genus Ruminiclostridium6 (OR: 0.474, 95% CI: 0.219–0.820, P = 0.011) had protective effects on PSC. In addition, we found the causal relationship of PSC with higher abundance of genus Dialister (beta: 0.059, 95% CI: 0.017–0.102, P = 0.006), genus Veillonella (beta: 0.065, 95% CI: 0.016–0.113, P = 0.009), class Melainabacteria (beta: 0.073, 95% CI: 0.012–0.133, P = 0.019), and order Gastranaerophilales (beta: 0.072, 95% CI: 0.011–0.113, P = 0.133). Conclusion: Our study reveals the causality between gut microbiota and PSC, providing new insights into the pathological mechanisms of PSC and facilitating the development of novel biomarkers and disease-modifying therapeutics for PSC from the perspective of gut microbiota.

Objective: Previous observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear.Methods: We explored the causal relationship between PDs and NTGDs through bidirectional two-sample Mendelian randomization (MR) study. Large-scale genome-wide association study (GWAS) summary statistics and bidirectional two-sample MR study were used to assess the causality between PDs and NTGDs. Multiple sensitivity analyses were used to identify the robustness of our results.Results: We found that major depression was causally associated with increased risk of gastric ulcer (OR: 1.812, 95% CI: 1.320–2.487, p < 0.001) and irritable bowel syndrome (OR: 1.645, 95% CI: 1.291–2.097, p < 0.001). Meanwhile, genetically predicted gastroesophageal reflux disease contributed to the increased risk of anxiety disorders (OR: 1.425, 95% CI: 1.295–1.568, p < 0.001), and ulcerative colitis was related to increased risk of attention deficit/hyperactivity disorder (OR: 1.042, 95% CI: 1.008–1.078, p = 0.0157).Conclusion: Our study provided MR evidence to support the close causality and identify the specific direction between eight PDs and eight common NTGDs. Experimental studies to further examine the causality, underlying mechanism, and therapeutic potential of PDs and NTGDs are required.

Background: Upper gastrointestinal (GI) diseases, including gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastritis and duodenitis (GD), stomach cancer, and esophageal cancer, pose significant global health and economic challenges. This study analyzes their trends, regional disparities, risk factors, and future projections from 1990 to 2046. Methods: Using the 2021 Global Burden of Disease database, we analyzed incidence, prevalence, mortality, and disability-adjusted life years (DALYs) across 204 countries, 21 regions, and five Socio-demographic Index (SDI) levels. Temporal trends were assessed with estimated annual percentage change and joinpoint regression. Decomposition analysis evaluated the contributions of population growth, aging, and epidemiological changes to changes in absolute disease burden. Risk-attributable fractions identified socioeconomic and behavioral factors, and Bayesian models projected future burdens. Results: From 1990 to 2021, global burdens of PUD, GD, stomach cancer, and esophageal cancer decreased, while GERD increased, particularly in middle SDI regions. Regional and sex disparities persisted, with higher burdens in lower SDI areas. Aging drove absolute disease burden in high-middle SDI regions, while population growth dominated in lower SDI regions. Smoking and alcohol significantly contributed to upper GI cancers. Projections suggest continued GERD increases and a modest PUD rebound, especially in aging and resource-limited populations. Conclusion: Evolving upper GI disease patterns highlight persistent health inequities. Targeted public health interventions are essential to mitigate future burdens and promote equitable digestive health outcomes globally.