Causal associations between gut microbiota and premature rupture of membranes: a two-sample Mendelian randomization study.

Previous study has indicated a potential link between gut microbiota and maternal pregnancy outcomes. However, the causal relationship between gut microbiota and premature rupture of membranes (PROM) remains a topic of ongoing debate. A two-sample Mendelian Randomization (MR) study was used to investigate the relationship between gut microbiota and PROM. Genetic data on gut microbiota was obtained from the MiBioGen consortium's largest genome-wide association study (GWAS) (n=14,306). Genetic data on PROM (3011 cases and 104247 controls) were sourced from publicly available GWAS data from the Finnish National Biobank FinnGen consortium. Various methods including Inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were utilized to assess the causal relationship by calculating the odd ratio (OR) value and confidence interval (CI). Sensitivity analyses for quality control were performed using MR-Egger intercept tests, Cochran's Q tests, and leave-one-out analyses. The IVW method revealed that class Mollicutes (IVW, OR=0.773, 95%CI: 0.61-0.981, pval = 0.034), genus Marvinbryantia (IVW, OR=00.736, 95%CI: 0.555-0.977, pval = 0.034), genus Ruminooccaceae UCG003 (IVW, OR=0.734, 95%CI: 0.568-0.947, pval = 0.017) and phylum Tenericutes (IVW, OR=0.773, 95%CI: 0.566-1.067, pval = 0.034) were associated with a reduced risk of PROM, while genus Collinsella (IVW, OR=1.444, 95%CI: 1.028-2.026, pval = 0.034), genus Intestinibacter (IVW, OR=1.304, 95%CI: 1.047-1.623, pval = 0.018) and genus Turicibacter (IVW, OR=1.282, 95%CI: 1.02-1.611, pval = 0.033) increased the risk of PROM. Based on the other four supplementary methods, six gut microbiota may have a potential effect on PROM. Due to the presence of pleiotropy (pval=0.045), genus Lachnoclostridium should be ruled out. No evidence of horizontal pleiotropy or heterogeneity was found in other microbiota (pval >0.05). In this study, we have discovered a causal relationship between the presence of specific probiotics and pathogens in the host and the risk of PROM. The identification of specific gut microbiota associated with PROM through MR studies offers a novel approach to diagnosing and treating this condition, thereby providing a new strategy for clinically preventing PROM.

Zhang L ，Li Q ，Huang J ，Zou Q ，Zou H ，Zhang X ，Su Y ，Li C ... -  《Frontiers in Immunology》

Gut microbiota and autism spectrum disorders: a bidirectional Mendelian randomization study.

Li Z ，Liu S ，Liu F ，Dai N ，Liang R ，Lv S ，Bao L ... -  《Frontiers in Cellular and Infection Microbiology》

Two-sample Mendelian randomization to study the causal association between gut microbiota and atherosclerosis.

According to some recent observational studies, the gut microbiota influences atherosclerosis via the gut microbiota-artery axis. However, the causal role of the gut microbiota in atherosclerosis remains unclear. Therefore, we used a Mendelian randomization (MR) strategy to try to dissect this causative link. The biggest known genome-wide association study (GWAS) (n = 13,266) from the MiBioGen collaboration was used to provide summary data on the gut microbiota for a two-sample MR research. Data on atherosclerosis were obtained from publicly available GWAS data from the FinnGen consortium, including cerebral atherosclerosis (104 cases and 218,688 controls), coronary atherosclerosis (23,363 cases and 187,840 controls), and peripheral atherosclerosis (6631 cases and 162,201 controls). The causal link between gut microbiota and atherosclerosis was investigated using inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode approaches, among which inverse variance weighting was the main research method. Cochran's Q statistic was used to quantify the heterogeneity of instrumental variables (IVs), and the MR Egger intercept test was used to assess the pleiotropy of IVs. Inverse-variance-weighted (IVW) estimation showed that genus Ruminiclostridium 9 had a protective influence on cerebral atherosclerosis (OR = 0.10, 95% CI: 0.01-0.67, P = 0.018), while family Rikenellaceae (OR = 5.39, 95% CI: 1.50-19.37, P = 0.010), family Streptococcaceae (OR = 6.87, 95% CI: 1.60-29.49, P = 0.010), genus Paraprevotella (OR = 2.88, 95% CI: 1.18-7.05, P = 0.021), and genus Streptococcus (OR = 5.26, 95% CI: 1.28-21.61, P = 0.021) had pathogenic effects on cerebral atherosclerosis. For family Acidaminococcaceae (OR = 0.87, 95% CI: 0.76-0.99, P = 0.039), the genus Desulfovibrio (OR = 0.89, 95% CI: 0.80-1.00, P = 0.048), the genus RuminococcaceaeUCG010 (OR = 0.80, 95% CI: 0.69-0.94, P = 0.006), and the Firmicutes phyla (OR = 0.87, 95% CI: 0.77-0.98, P = 0.023) were protective against coronary atherosclerosis. However, the genus Catenibacterium (OR = 1.12, 95% CI: 1.00-1.24, P = 0.049) had a pathogenic effect on coronary atherosclerosis. Finally, class Actinobacteria (OR = 0.83, 95% CI: 0.69-0.99, P = 0.036), family Acidaminococcaceae (OR = 0.76, 95% CI: 0.61-0.94, P = 0.013), genus Coprococcus2 (OR = 0.76, 95% CI: 0.60-0.96, P = 0.022), and genus RuminococcaceaeUCG010 (OR = 0.65, 95% CI: 0.46-0.92, P = 0.013), these four microbiota have a protective effect on peripheral atherosclerosis. However, for the genus Lachnoclostridium (OR = 1.25, 95% CI: 1.01-1.56, P = 0.040) and the genus LachnospiraceaeUCG001 (OR = 1.22, 95% CI: 1.04-1.42, P = 0.016), there is a pathogenic role for peripheral atherosclerosis. No heterogeneity was found for instrumental variables, and no considerable horizontal pleiotropy was observed. We discovered that the presence of probiotics and pathogens in the host is causally associated with atherosclerosis, and atherosclerosis at different sites is causally linked to specific gut microbiota. The specific gut microbiota associated with atherosclerosis identified by Mendelian randomization studies provides precise clinical targets for the treatment of atherosclerosis. In the future, we can further examine the gut microbiota's therapeutic potential for atherosclerosis if we have a better grasp of the causal relationship between it and atherosclerosis.

Jiang S ，Yu C ，Lv B ，He S ，Zheng Y ，Yang W ，Wang B ，Li D ，Lin J ... -  《Frontiers in Immunology》

Uncovering a causal connection between the Lachnoclostridium genus in fecal microbiota and non-alcoholic fatty liver disease: a two-sample Mendelian randomization analysis.

Dai W ，Cai D ，Zhou S ，Li A ，Xie J ，Zhang J ... -  《Frontiers in Microbiology》

Association between gut microbiota and spinal stenosis: a two-sample mendelian randomization study.

Considerable evidence has unveiled a potential correlation between gut microbiota and spinal degenerative diseases. However, only limited studies have reported the direct association between gut microbiota and spinal stenosis. Hence, in this study, we aimed to clarify this relationship using a two-sample mendelian randomization (MR) approach. Data for two-sample MR studies was collected and summarized from genome-wide association studies (GWAS) of gut microbiota (MiBioGen, n = 13, 266) and spinal stenosis (FinnGen Biobank, 9, 169 cases and 164, 682 controls). The inverse variance-weighted meta-analysis (IVW), complemented with weighted median, MR-Egger, weighted mode, and simple mode, was used to elucidate the causality between gut microbiota and spinal stenosis. In addition, we employed mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and the MR-Egger intercept test to assess horizontal multiplicity. Cochran's Q test to evaluate heterogeneity, and "leave-one-out" sensitivity analysis to determine the reliability of causality. Finally, an inverse MR analysis was performed to assess the reverse causality. The IVW results indicated that two gut microbial taxa, the genus Eubacterium fissicatena group and the genus Oxalobacter, have a potential causal relationship with spinal stenosis. Moreover, eight potential associations between genetic liability of the gut microbiota and spinal stenosis were implied. No significant heterogeneity of instrumental variables or horizontal pleiotropy were detected. In addition, "leave-one-out" sensitivity analysis confirmed the reliability of causality. Finally, the reverse MR analysis revealed that no proof to substantiate the discernible causative relationship between spinal stenosis and gut microbiota. This analysis demonstrated a possible causal relationship between certain particular gut microbiota and the occurrence of spinal stenosis. Further studies focused on the mechanism of gut microbiota-mediated spinal stenosis can lay the groundwork for targeted prevention, monitoring, and treatment of spinal stenosis.

Li J ，Wei J ，Wang J ，Xu T ，Wu B ，Yang S ，Jing S ，Wu H ，Hao H ... -  《Frontiers in Immunology》