Background: Growing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship.Objective: To reveal the causal association between gut microbiota and AD, we conducted a two-sample Mendelian randomization (MR) analysis.Materials and Methods: We assessed genome-wide association study (GWAS) summary statistics for gut microbiota and six common ADs, namely, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes (T1D), and celiac disease (CeD), from published GWASs. Two-sample MR analyses were first performed to identify causal bacterial taxa for ADs in discovery samples. Significant bacterial taxa were further replicated in independent replication outcome samples. A series of sensitivity analyses was performed to validate the robustness of the results. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation.Results: Combining the results from the discovery and replication stages, we identified one causal bacterial genus, Bifidobacterium. A higher relative abundance of the Bifidobacterium genus was associated with a higher risk of T1D [odds ratio (OR): 1.605; 95% CI, 1.339–1.922; P_FDR = 4.19 × 10⁻⁷] and CeD (OR: 1.401; 95% CI, 1.139–1.722; P_FDR = 2.03 × 10⁻³), respectively. Further sensitivity analyses validated the robustness of the above associations. The results of reverse MR analysis showed no evidence of reverse causality from T1D and CeD to the Bifidobacterium genus.Conclusion: This study implied a causal relationship between the Bifidobacterium genus and T1D and CeD, thus providing novel insights into the gut microbiota-mediated development mechanism of ADs.

Appendicular lean mass (ALM) is a heritable trait associated with loss of lean muscle mass and strength, or sarcopenia, but its genetic determinants are largely unknown. Here we conducted a genome-wide association study (GWAS) with 450,243 UK Biobank participants to uncover its genetic architecture. A total of 1059 conditionally independent variants from 799 loci were identified at the genome-wide significance level (p < 5 × 10⁻⁹), all of which were also significant at p < 5 × 10^–5 in both sexes. These variants explained ~15.5% of the phenotypic variance, accounting for more than one quarter of the total ~50% GWAS-attributable heritability. There was no difference in genetic effect between sexes or among different age strata. Heritability was enriched in certain functional categories, such as conserved and coding regions, and in tissues related to the musculoskeletal system. Polygenic risk score prediction well distinguished participants with high and low ALM. The findings are important not only for lean mass but also for other complex diseases, such as type 2 diabetes, as ALM is shown to be a protective factor for type 2 diabetes.

Objective: The purpose of the present study was to evaluate the effectiveness of probiotics on type II diabetes mellitus (T2DM).Methods: We performed a comprehensive search on PubMed, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journal Databases, Wan Fang database and China biology medicine disc for relevant studies published before June 2019. Glycated hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR) and fasting blood glucose (FBG) were used as indicators for T2DM. Inverse-variance weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for the mean HbA1c, FBG and HOMA-IR changes from baseline.Results: 15 randomized controlled trials (RCT) with a total of 902 participants were included into the meta-analysis. Considering the clinical heterogeneity caused by variation of dosage and duration of probiotic treatment, random-effects model was used to estimate the pooled WMD. Significantly greater reduction in HbA1c% (WMD = − 0.24, 95% CI [− 0.44, − 0.04],p = 0.02), FBG (WMD = − 0.44 mmol/L, 95% CI [− 0.74, − 0.15],p = 0.003) and HOMA-IR (WMD = − 1.07, 95% CI [− 1.58, − 0.56],p < 0.00001) were observed in probiotics treated group. Further sensitivity analysis verified the reliability and stability of our results.Conclusion: The results of our meta-analysis indicated that probiotics treatment may reduce HbA1c, FBG and insulin resistance level in T2DM patients. More clinical data and research into the mechanism of probiotics are needed to clarify the role of probiotics in T2DM.

Although recent studies have revealed an association between the composition of the gut microbiota and obesity, whether specific gut microbiota cause obesity has not been determined. The aim of this study is to determine the causal relationship between specific gut microbiota and abdominal obesity. Based on genome-wide association study (GWAS) summary statistics, we performed a 2-sample Mendelian randomization (MR) analysis to evaluate whether the gut microbiota affects abdominal obesity. Gut microbiota GWAS in 1126 twin pairs (age range, 18–89 years; 89% were females) from the TwinsUK study were used as exposure data. The primary outcome tested was trunk fat mass (TFM) GWAS in 492,805 participants (age range, 40–69 years; 54% were females) from the UK Biobank. The gut microbiota were classified at family, genus, and species levels. A feature was defined as a distinct family, genus, or species. MR analysis was mainly performed by an inverse variance–weighted test or Wald ratio test, depending on the number of instrumental variables (IVs) involved. A sensitivity analysis was performed on significant results by a weighted median test and a weighted genetic risk score (GRS) analysis. Results of MR analyses provided evidence of a causal association between 3 microbiota features and TFM, including 1 family [Lachnosiraceae; P = 0.02; β = 0.001 (SEE, 4.28 × 10⁻⁴)], 1 genus [Bifidobacterium; P = 5.0 × 10⁻⁹; β = −0.08 (SEE, 0.14)], and 1 species [Prausnitzii; P = 0.03; β = −0.007 (SEE, 0.003)]. Both the weighted median test and GRS analysis successfully validated the association of the genetically predicted family, Lachnosiraceae (P_{weighted median} = 0.03; P_GRS = 0.004). Our findings provided evidence of a causal association between gut microbiota and TFM in UK adults and identified specific bacteria taxa that may regulate the fat metabolism, thus offering new direction for the treatment of obesity.