Bacteroidaceae, Bacteroides, and Veillonella: emerging protectors against Graves' disease.

Graves' disease (GD) is the most common cause of hyperthyroidism, and its pathogenesis remains incompletely elucidated. Numerous studies have implicated the gut microbiota in the development of thyroid disorders. This study employs Mendelian randomization analysis to investigate the characteristics of gut microbiota in GD patients, aiming to offer novel insights into the etiology and treatment of Graves' disease. Two-sample Mendelian randomization (MR) analysis was employed to assess the causal relationship between Graves' disease and the gut microbiota composition. Gut microbiota data were sourced from the international consortium MiBioGen, while Graves' disease data were obtained from FINNGEN. Eligible single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Multiple analysis methods, including inverse variance-weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-RAPS, were utilized. Sensitivity analyses were conducted employing MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis as quality control measures. The Mendelian randomization study conducted in a European population revealed a decreased risk of Graves' disease associated with Bacteroidaceae (Odds ratio (OR) [95% confidence interval (CI)]: 0.89 [0.89 ~ 0.90], adjusted P value: <0.001), Bacteroides (OR: [95% CI]: 0.555 [0.437 ~ 0.706], adjusted P value: <0.001), and Veillonella (OR [95% CI]: 0.632 [0.492 ~ 0.811], adjusted P value: 0.016). No significant evidence of heterogeneity, or horizontal pleiotropy was detected. Furthermore, the preliminary MR analysis identified 13 bacterial species including Eubacterium brachy group and Family XIII AD3011 group, exhibiting significant associations with Graves' disease onset, suggesting potential causal effects. A causal relationship exists between gut microbiota and Graves' disease. Bacteroidaceae, Bacteroides, and Veillonella emerge as protective factors against Graves' disease development. Prospective probiotic supplementation may offer a novel avenue for adjunctive treatment in the management of Graves' disease in the future.

Liu S ，Li F ，Cai Y ，Ren L ，Sun L ，Gang X ，Wang G ... -  《Frontiers in Cellular and Infection Microbiology》

Unraveling the mystery: a Mendelian randomized exploration of gut microbiota and different types of obesity.

Numerous studies have demonstrated the influence of gut microbiota on the development of obesity. In this study, we utilized Mendelian randomization (MR) analysis to investigate the gut microbiota characteristics among different types of obese patients, aiming to elucidate the underlying mechanisms and provide novel insights for obesity treatment. Two-sample multivariable Mendelian randomization (MR) analysis was employed to assess causal relationships between gut microbiota and various obesity subtypes. Gut microbiota data were obtained from the international consortium MiBioGen, and data on obese individuals were sourced from the Finnish National Biobank FinnGen. Eligible single-nucleotide polymorphisms (SNPs) were selected as instrumental variables. Various analytical methods, including inverse variance weighted (IVW), MR-Egger regression, weighted median, MR-RAPS, and Lasso regression, were applied. Sensitivity analyses for quality control included MR-Egger intercept tests, Cochran's Q tests, and leave-one-out analyses and others. Mendelian randomization studies revealed distinct gut microbiota profiles among European populations with different obesity subtypes. Following multivariable MR analysis, we found that Ruminococcaceae UCG010 [Odds Ratio (OR): 0.842, 95% confidence interval (CI): 0.766-0.926, Adjusted P value: 0.028] independently reduced the risk of obesity induced by excessive calorie intake, while Butyricimonas [OR: 4.252, 95% CI: 2.177-8.307, Adjusted P value: 0.002] independently increased the risk of medication-induced obesity. For localized adiposity, Pasteurellaceae [OR: 0.213, 95% CI: 0.115-0.395, Adjusted P value: <0.001] acted as a protective factor. In the case of extreme obesity with alveolar hypoventilation, lactobacillus [OR: 0.724, 95% CI: 0.609-0.860, Adjusted P value: 0.035] reduced the risk of its occurrence. Additionally, six gut microbiota may have potential roles in the onset of different types of obesity. Specifically, the Ruminococcus torques group may increase the risk of its occurrence. Desulfovibrio and Catenabacterium may serve as protective factors in the onset of Drug-induced obesity. Oxalobacteraceae, Actinomycetaceae, and Ruminiclostridium 9, on the other hand, could potentially increase the risk of Drug-induced obesity. No evidence of heterogeneity or horizontal pleiotropy among SNPs was found in the above studies (all P values for Q test and MR-Egger intercept > 0.05). Gut microbiota abundance is causally related to obesity, with distinct gut microbiota profiles observed among different obesity subtypes. Four bacterial species, including Ruminococcaceae UCG010, Butyricimonas, Pasteurellaceae and lactobacillus independently influence the development of various types of obesity. Probiotic and prebiotic supplementation may represent a novel approach in future obesity management.

Liu S ，Li F ，Cai Y ，Ren L ，Sun L ，Gang X ，Wang G ... -  《-》

The Causal Relationship between the Morning Chronotype and the Gut Microbiota: A Bidirectional Two-Sample Mendelian Randomization Study.

Chen M ，Wang Z ，Tan DS ，Wang X ，Ye Z ，Xie Z ，Zhang D ，Wu D ，Zhao Y ，Qu Y ，Jiang Y ... -  《Nutrients》

Causal effects of gut microbiota on chalazion: a two-sample Mendelian randomization study.

To investigate the causal relationship between gut microbiota (GM) and chalazion through Mendelian randomization (MR) analysis. GM-related genome-wide association studies (GWAS) were obtained from the International Consortium MiBioGen. Genetic data for chalazion were sourced from the MRC Integrative Epidemiology Unit (IEU) Open GWAS database. Five MR methods, including inverse variance weighted (IVW), were employed to estimate causal relationships. Cochran's Q test was used to detect heterogeneity, the MR-Egger intercept test and MR-PRESSO regression were utilized to detect horizontal pleiotropy, and the leave-one-out method was employed to validate data stability. We identified 1,509 single nucleotide polymorphisms (SNPs) across 119 genera as instrumental variables (IVs) (p < 1 × 10-5). According to the inverse variance weighted (IVW) estimate, the Family XIII AD3011 group (OR = 1.0018, 95% CI 1.0002-1.0035, p = 0.030) and Catenibacterium (OR = 1.0013, 95% CI 1.0002-1.0025, p = 0.022) were potentially associated with increased risk of chalazion. Conversely, Veillonella (OR = 0.9986, 95% CI 0.9974-0.9999, p = 0.036) appeared to provide protection against chalazion. There was no evidence of heterogeneity or pleiotropy. This study uncovered the causal relationship between GM and chalazion, pinpointing Catenibacterium and Family XIII AD3011 group as potential risk contributors, while highlighting Veillonella as a protective factor. In-depth investigation into the potential mechanisms of specific bacteria in chalazion was essential for providing novel therapeutic and preventive strategies in the future.

Zhang W ，Gu X ，Zhao Q ，Wang C ，Liu X ，Chen Y ，Zhao X ... -  《Frontiers in Medicine》

Relationship between gut microbiota and thyroid function: a two-sample Mendelian randomization study.

Numerous observational studies have indicated a link between the composition of gut microbiota and thyroid function. Nevertheless, the precise causal relationship between gut microbiota and thyroid function remains uncertain. In this two-sample Mendelian randomization study, we utilized summary data from a genome-wide association study of gut microbiota composition in 18,340 participants from 24 cohorts, as well as summary statistics on thyroid hormones and thyroid-stimulating hormone from the ThyroidOmics Consortium and summary statistics on hypothyroidism and hyperthyroidism from the FinnGen R8 release. Five different methods, including inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode, were employed to examine the causal relationship between gut microbiota and thyroid function. Reverse Mendelian randomization analysis was conducted for taxa identified as having a causal relationship with thyroid function in the Mendelian randomization analysis. To assess the robustness of the results, sensitivity analyses were conducted employing Cochran's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. Through MR analysis of 211 microbial taxa and 4 phenotypes, we identified a total of 34 gut microbiota taxa that were associated with the outcomes. After using the bonferroni method for multiple testing correction, phylum Actinobacteria (id.400) had a protective effect on hypothyroidism (OR=0.883, 95% CI: 0.817-0.955, P=0.002), and class Deltaproteobacteria (id.3087) had a protective effect on hyperthyroidism (OR=0.549, 95% CI: 0.374-0.805, P=0.002). According to the results of reverse MR analysis, no significant causal effect of the four phenotypes was found on gut microbiota. No significant horizontal pleiotropy was detected based on MR-Egger intercept test and MR-PRESSO global test. Through two-sample MR analysis, we identified specific gut microbiota taxa at the genetic level that are predicted to have a causal relationship with thyroid function, which may serve as useful biomarkers for early disease diagnosis.

Xie L ，Zhao H ，Chen W 《Frontiers in Endocrinology》