Gut microbiota and oral cavity cancer: a two-sample bidirectional Mendelian randomization study.

This study employs a two-sample bidirectional Mendelian randomization (MR) approach to systematically evaluate the causal relationship between gut microbiota and oral cavity cancer (OCC). To address the challenge in establishing the causal relationship between gut microbiota and OCC, we applied a systematic MR analysis. Utilizing GWAS data from the MiBioGen consortium (18,340 individuals) and UK Biobank (n = 264,137), we selected instrumental variables and employed MR-Egger, weighted median, IVW, and weighted mode analyses. Heterogeneity and pleiotropy were assessed using Cochran's Q test and MR-Egger intercept test. Our findings indicate, at the order level, Bacteroidales (OR = 0.9990, 95% CI = 0.9980-1.0000, P = 0.046), Burkholderiales (OR = 1.0009, 95% CI = 1.0001-1.0018, P = 0.033), and Victivallales (OR = 0.9979, 95% CI = 0.9962-0.9995, P = 0.037) exhibit causality on OCC in the Weighted median, IVW, and MR-Egger analyses, respectively. At the family level, Alcaligenaceae (OR = 1.0012, 95% CI = 1.0004-1.0019, P = 0.002) and Clostridiaceae1 (OR = 0.9970, 95% CI = 0.9948-0.9992, P = 0.027) show causality on OCC in IVW and MR-Egger analyses. At the genus level, Clostridiumsensustricto1 (IVW, OR = 0.9987, 95% CI = 0.9980-0.9995, P = 0.001; MR-Egger, OR = 0.9978, 95% CI = 0.9962-0.9995, P = 0.035), Desulfovibrio (IVW, OR = 1.0008, 95% CI = 1.0001-1.0015, P = 0.016), Eggerthella (IVW, OR = 0.9995, 95% CI = 0.9990-1.0000, P = 0.048), Eubacterium fissicatena group (IVW, OR = 1.0005, 95% CI = 1.0000-1.0009, P = 0.032), and Holdemanella (IVW, OR = 0.9994, 95% CI = 0.9989-0.9999, P = 0.018) are implicated in causing OCC in related analyses. Our study identifies Burkholderiales order, Alcaligenaceae family, Desulfovibrio genus, and Eubacterium fissicatena group as causally increasing OCC risk. In contrast, Bacteroidales order, Victivallales order, Clostridiaceae1 family, Clostridiumsensustricto1 genus, Eggerthella genus, and Holdemanella genus are causally associated with a decreased OCC risk. However, further investigations are essential to delineate an optimal gut microbiota composition and unravel the underlying mechanisms of specific bacterial taxa in OCC pathophysiology.

Sun Z ，Bai C ，Hao D ，Jiang X ，Chen J ... -  《Frontiers in Oncology》

Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study.

The real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D. We leveraged publicly available genome-wide association study (GWAS) summary data to perform MR analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen were used. The summary statistic data for T1D (n = 264,137) were obtained from the latest release from the FinnGen consortium as the outcome of interest. The selection of instrumental variables conformed strictly to a series of preset inclusion and exclusion criteria. MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods were used to assess the causal association. The Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. At the phylum level, only Bacteroidetes was indicated to have causality on T1D (OR = 1.24, 95% CI = 1.01-1.53, P = 0.044) in the IVW analysis. When it comes to their subcategories, Bacteroidia class (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P FDR = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P FDR = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10-4, P FDR = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected. The present study reports that Bacteroidetes phylum, Bacteroidia class, and Bacteroidales order causally increase T1D risk, whereas Eubacterium eligens group genus, which belongs to the Firmicutes phylum, causally decreases T1D risk. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa's role in the pathophysiology of T1D.

Luo M ，Sun M ，Wang T ，Zhang S ，Song X ，Liu X ，Wei J ，Chen Q ，Zhong T ，Qin J ... -  《Frontiers in Cellular and Infection Microbiology》

Causal relationship between gut microbiota with subcutaneous and visceral adipose tissue: a bidirectional two-sample Mendelian Randomization study.

Numerous studies have revealed associations between gut microbiota and adipose tissue. However, the specific functional bacterial taxa and their causal relationships with adipose tissue production in different regions of the body remain unclear. We conducted a bidirectional two-sample Mendelian Randomization (MR) study using aggregated data from genome-wide association studies (GWAS) for gut microbiota and adipose tissue. We employed methods such as inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode to assess the causal relationships between gut microbiota and subcutaneous adipose tissue (SAT) as well as visceral adipose tissue (VAT). Cochran's Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to test for heterogeneity, pleiotropy, and outliers of the instrumental variables, respectively. Reverse MR was employed to evaluate the reverse causal relationships between SAT, VAT, and gut microbiota with significant associations. IVW results demonstrated that Betaproteobacteria were protective factors for SAT production (OR = 0.88, 95% CI: 0.80-0.96, p = 0.005) and VAT production (OR = 0.91, 95% CI: 0.83-0.99, p = 0.030). Various bacterial taxa including Ruminococcaceae UCG002 (OR = 0.94, 95% CI: 0.89-0.99, p = 0.017), Methanobacteria class (OR = 0.96, 95% CI: 0.92-1.00, p = 0.029), and Burkholderiales (OR = 0.90, 95% CI: 0.83-0.98, p = 0.012) were associated only with decreased SAT production. Rikenellaceae RC9 gut group (OR = 1.05, 95% CI: 1.02-1.10, p = 0.005), Eubacterium hallii group (OR = 1.08, 95% CI: 1.01-1.15, p = 0.028), Peptococcaceae (OR = 1.08, 95% CI: 1.01-1.17, p = 0.034), and Peptococcus (OR = 1.05, 95% CI: 1.00-1.10, p = 0.047) were risk factors for SAT production. Meanwhile, Eubacterium fissicatena group (OR = 0.95, 95% CI: 0.91-0.99, p = 0.019), Turicibacter (OR = 0.93, 95% CI: 0.88-0.99, p = 0.022), and Defluviitaleaceae UCG011 (OR = 0.94, 95% CI: 0.89-0.99, p = 0.024) were protective factors for VAT production. Furthermore, Bacteroidetes (OR = 1.09, 95% CI: 1.01-1.17, p = 0.018), Eubacterium eligens group (OR = 1.09, 95% CI: 1.01-1.19, p = 0.037), Alloprevotella (OR = 1.05, 95% CI: 1.00-1.10, p = 0.038), and Phascolarctobacterium (OR = 1.07, 95% CI: 1.00-1.15, p = 0.042) were associated with VAT accumulation. Additionally, reverse MR revealed significant associations between SAT, VAT, and Rikenellaceae RC9 gut group (IVW: OR = 1.57, 95% CI: 1.18-2.09, p = 0.002) as well as Betaproteobacteria (IVW: OR = 1.14, 95% CI: 1.01-1.29, p = 0.029), both acting as risk factors. Sensitivity analyzes during bidirectional MR did not identify heterogeneity or pleiotropy. This study unveils complex causal relationships between gut microbiota and SAT/VAT, providing novel insights into the diagnostic and therapeutic potential of gut microbiota in obesity and related metabolic disorders.

Cao F ，Pan F ，Gong X ，Wang W ，Xu Y ，Cao P ，Wang Y ... -  《-》

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》

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》