Potential effects of specific gut microbiota on periodontal disease: a two-sample bidirectional Mendelian randomization study
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SUBMITTER: Xu M
PROVIDER: S-EPMC10834673 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Background Recent observational studies and clinical trials demonstrated an association between gut microbiota and musculoskeletal (MSK) diseases. Nonetheless, whether the gut microbiota composition has a causal effect on the risk of MSK diseases remains unclear. Methods Based on large-scale genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between gut microbiota and six MSK diseases, namely osteoporosis (OP), fracture, sarcopenia, low back pain (LBP), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Instrumental variables for 211 gut microbiota taxa were obtained from the largest available GWAS meta-analysis (n = 18,340) conducted by the MiBioGen consortium. And the summary-level data for six MSK diseases were derived from published GWAS. The inverse-variance weighted (IVW) method was conducted as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses using multiple methods. The Bonferroni-corrected test was used to determine the strength of the causal relationship between gut microbiota and various MSK diseases. Finally, a reverse MR analysis was applied to evaluate reverse causality. Results According to the IVW method, we found 57 suggestive causal relationships and 3 significant causal relationships between gut microbiota and MSK diseases. Among them, Genus Bifidobacterium (β: 0.035, 95% CI: 0.013–0.058, p = 0.0002) was associated with increased left handgrip strength, Genus Oxalobacter (OR: 1.151, 95% CI: 1.065–1.245, p = 0.0003) was correlated with an increased risk of LBP, and Family Oxalobacteraceae (OR: 0.792, 95% CI: 0.698–0.899, p = 0.0003) was linked with a decreased risk of RA. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy, or outliers for the causal effect of specific gut microbiota on MSK diseases (p > 0.05). Reverse MR analysis showed fracture may result in a higher abundance of Family Bacteroidales (p = 0.030) and sarcopenia may lead to a higher abundance of Genus Sellimonas (p = 0.032). Conclusion Genetic evidence suggested a causal relationship between specific bacteria taxa and six MSK diseases, which highlights the association of the “gut-bone/muscle” axis. Further exploration of the potential microbiota-related mechanisms of bone and muscle metabolism might provide novel insights into the prevention and treatment of MSK diseases.
| S-EPMC10469765 | biostudies-literature
Project description:BackgroundAlthough previous studies have suggested a close association between gut microbiota (GM) and intervertebral disc degeneration (IVDD), the causal relationship between them remains unclear. Hence, we thoroughly investigate their causal relationship by means of a two-sample Mendelian randomization (MR) study, aiming to determine the impact of gut microbiota on the risk of developing intervertebral disc degeneration.MethodsSummary data from genome-wide association studies of GM (the MiBioGen) and IVDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. A reverse MR analysis was conducted to assess potential reverse causation.ResultsWe identified nine gut microbial taxa that were causally associated with IVDD (P < 0.05). Following the Benjamini-Hochberg corrected test, the association between the phylum Bacteroidetes and a higher risk of IVDD remained significant (IVW FDR-corrected P = 0.0365). The results of the Cochrane Q test did not indicate heterogeneity (P > 0.05). Additionally, both the MR-Egger intercept test and the MR-PRESSO global test revealed that our results were not influenced by horizontal pleiotropy (P > 0.05). Furthermore, the leave-one-out analysis substantiated the reliability of the causal relationship. In the reverse analysis, no evidence was found to suggest that IVDD has an impact on the gut microbiota.ConclusionOur results validate the potential causal impact of particular GM taxa on IVDD, thus providing fresh insights into the gut microbiota-mediated mechanism of IVDD and laying the groundwork for further research into targeted preventive measures.
| S-EPMC10424333 | biostudies-literature
Project description:BackgroundPrevious observational studies have indicated a correlation between the gut microbiota and influenza; however, the exact nature of the bidirectional causal connection remains uncertain.MethodA two-way, two-sample Mendelian randomization (MR) study was conducted to evaluate the possible causal connection between the gut microbiota and the two outcomes of influenza (pneumonia without influenza and influenza pneumonia). The statistical analysis of gut microbiota is derived from the information of the most extensive meta-analysis (GWAS) conducted by the MiBioGen Alliance, encompassing a sample size of 18,340.The summary statistical data for influenza (not pneumonia, n = 291,090) and influenza pneumonia (n = 342,499) are from GWAS data published by FinnGen consortium R8.Estimate and summarize Single-nucleotide polymorphisms (SNPs) using Inverse variance weighted (IVW), MR Egger, and Weighted median (WM) in bidirectional MR analysis. To assess the heterogeneity, horizontal pleiotropy, and stability of SNPs, we employed Cochran's Q test, MR Egger intercept test, and sensitivity analysis.ResultThe IVW analysis indicated that there was a significant association between influenza infection and five bacterial taxa. Additionally, the abundance changes of seven gut microbiota were found to be causally related to influenza infection. In addition, seven bacterial taxa showed a significant association with the occurrence of influenza pneumonia. The findings from the WM analysis largely support the outcomes of IVW, however, the results of MR egger analysis do not align with IVW. Furthermore, there is no proof to substantiate the cause-and-effect relationship between influenza pneumonia and the composition of gut microbiota.ConclusionThis analysis demonstrates a possible bidirectional causal connection between the prevalence of particular gut microbiota and the occurrence of influenza infection. The presence of certain gut microbiota may potentially contribute to the development of pneumonia caused by influenza. Additional investigation into the interaction between particular bacterial communities and influenza can enhance efforts in preventing, monitoring, and treating influenza.
| S-EPMC10580584 | biostudies-literature
Project description:IntroductionPrevious research has reported that the gut microbiota performs an essential role in sleep through the microbiome-gut-brain axis. However, the causal association between gut microbiota and sleep remains undetermined.MethodsWe performed a two-sample, bidirectional Mendelian randomization (MR) analysis using genome-wide association study summary data of gut microbiota and self-reported sleep traits from the MiBioGen consortium and UK Biobank to investigate causal relationships between 119 bacterial genera and seven sleep-associated traits. We calculated effect estimates by using the inverse-variance weighted (as the main method), maximum likelihood, simple model, weighted model, weighted median, and MR-Egger methods, whereas heterogeneity and pleiotropy were detected and measured by the MR pleiotropy residual sum and outlier method, Cochran's Q statistics, and MR-Egger regression.ResultsIn forward MR analysis, inverse-variance weighted estimates concluded that the genetic forecasts of relative abundance of 42 bacterial genera had causal effects on sleep-associated traits. In the reverse MR analysis, sleep-associated traits had a causal effect on 39 bacterial genera, 13 of which overlapped with the bacterial genera in the forward MR analysis.DiscussionIn conclusion, our research indicates that gut microbiota may be involved in the regulation of sleep, and conversely, changes in sleep-associated traits may also alter the abundance of gut microbiota. These findings suggest an underlying reciprocal causal association between gut microbiota and sleep.
| S-EPMC10461450 | biostudies-literature
Project description:ObjectiveThe 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.MethodsWe 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.ResultsAt 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.ConclusionsThe 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.
| S-EPMC10258312 | biostudies-literature
Project description:BackgroundGrowing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional.MethodsA bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method.ResultsIn the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found.ConclusionOur study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.
| S-EPMC10765819 | biostudies-literature
Project description:BackgroundRecent studies have suggested a relationship between gut microbiota and non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). However, the nature and direction of this potential causal relationship are still unclear. This study used two-sample Mendelian randomization (MR) to clarify the potential causal links.MethodsSummary-level Genome-Wide Association Studies (GWAS) statistical data for gut microbiota and NAFLD/NASH were obtained from MiBioGen and FinnGen respectively. The MR analyses were performed mainly using the inverse-variance weighted (IVW) method, with sensitivity analyses conducted to verify the robustness. Additionally, reverse MR analyses were performed to examine any potential reverse causal associations.ResultsOur analysis, primarily based on the IVW method, strongly supports the existence of causal relationships between four microbial taxa and NAFLD, and four taxa with NASH. Specifically, associations were observed between Enterobacteriales (P =0.04), Enterobacteriaceae (P =0.04), Lachnospiraceae UCG-004 (P =0.02), and Prevotella9 (P =0.04) and increased risk of NAFLD. Dorea (P =0.03) and Veillonella (P =0.04) could increase the risks of NASH while Oscillospira (P =0.04) and Ruminococcaceae UCG-013 (P=0.005) could decrease them. We also identified that NAFLD was found to potentially cause an increased abundance in Holdemania (P =0.007) and Ruminococcus2 (P =0.002). However, we found no evidence of reverse causation in the microbial taxa associations with NASH.ConclusionThis study identified several specific gut microbiota that are causally related to NAFLD and NASH. Observations herein may provide promising theoretical groundwork for potential prevention and treatment strategies for NAFLD and its progression to NASH in future.
| S-EPMC10722258 | biostudies-literature
Project description:Recent studies have shown altered gut microbiome composition in patients with scoliosis. However, the causal effect of gut microbiota on scoliosis remains unknown. A Mendelian randomization (MR) study was conducted to quantify the impact of 191 gut microbiome taxa's instrumental variables from the MibioGen Genome-wide association study (GWAS) on scoliosis risk using data from the FinnGen GWAS (1168 cases and 16,4682 controls). Inverse variance weighted (IVW) was the main method, and MR results were verified by sensitive analysis. Bilophila, Eubacterium (eligens group), Prevotella9, and Ruminococcus2 were discovered to have a protective effect on the risk of scoliosis. Ruminococcaceae UCG009, Catenibacterium, Coprococcus2, Eubacterium (ventriosum group), Lachnospiraceae (FCS020 group), Ruminiclostridium6, and Mollicutes RF9 may increase the occurrence of scoliosis. Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analysis confirmed the robustness of the MR results. Our study identified four protective bacteria taxa on scoliosis and seven microbiota that may increase scoliosis occurrence. Further MR analysis is required to corroborate our findings, using a more sophisticated technique to obtain estimates with less bias and greater precision or GWAS summary data with more gut microbiome and scoliosis patients.
| S-EPMC10641244 | biostudies-literature
Project description:BackgroundSeveral studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal relationship between GM and HSCR remains unknown.MethodsIn this study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between GM and HSCR, based on the MiBioGen Consortium's genome-wide association study (GWAS) and the GWAS Catalog's HSCR data. Reverse MR analysis was performed subsequently, and the sensitivity analysis, Cochran's Q-test, MR pleiotropy residual sum, outlier (MR-PRESSO), and the MR-Egger intercept were used to analyze heterogeneity or horizontal pleiotropy. 16S rDNA sequencing and targeted mass spectrometry were developed for initial validation.ResultsIn the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23-5.74, p = 0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18-0.73, p = 0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11-0.91, p = 0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06-0.78, p = 0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09-0.8, p = 0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04-0.66, p = 0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21-0.98, p = 0.04) were protective factors for HSCR, which had no heterogeneity or horizontal pleiotropy. However, reverse MR analysis showed that HSCR (OR: 1.02, 95%CI: 1-1.03, p = 0.049) is the risk factor for Eggerthella. Furthermore, some of the above microbiota and short-chain fatty acids (SCFAs) were altered in HSCR, showing a correlation.ConclusionOur analysis established the relationship between specific GM and HSCR, identifying specific bacteria as protective or risk factors. Significant microbiota and SCFAs were altered in HSCR, underlining the importance of further study and providing new insights into the pathogenesis and treatment.
| S-EPMC10956417 | biostudies-literature
Project description:BackgroundNicotine dependence is a key factor influencing the diversity of gut microbiota, and targeting gut microbiota may become a new approach for the prevention and treatment of nicotine dependence. However, the causal relationship between the two is still unclear. This study aims to investigate the causal relationship between nicotine dependence and gut microbiota.MethodsA two-sample bidirectional Mendelian randomization (MR) study was conducted using the largest existing gut microbiota and nicotine dependence genome-wide association studies (GWAS). Causal relationships between genetically predicted nicotine dependence and gut microbiota abundance were examined using inverse variance weighted, MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO approaches. Cochrane's Q test, MR-Egger intercept test, and leave-one-out analysis were performed as sensitivity analyses to assess the robustness of the results. Multivariable Mendelian randomization analysis was also conducted to eliminate the interference of smoking-related phenotypes. Reverse Mendelian randomization analysis was then performed to determine the causal relationship between genetically predicted gut microbiota abundance and nicotine dependence.ResultsGenetically predicted nicotine dependence had a causal effect on Christensenellaceae (β: -0.52, 95% CI: -0.934-0.106, P = 0.014). The Eubacterium xylanophilum group (OR: 1.106, 95% CI: 1.004-1.218), Lachnoclostridium (OR: 1.118, 95% CI: 1.001-1.249) and Holdemania (OR: 1.08, 95% CI: 1.001-1.167) were risk factors for nicotine dependence. Peptostreptococcaceae (OR: 0.905, 95% CI: 0.837-0.977), Desulfovibrio (OR: 0.014, 95% CI: 0.819-0.977), Dorea (OR: 0.841, 95% CI. 0.731-0.968), Faecalibacterium (OR: 0.831, 95% CI: 0.735-0.939) and Sutterella (OR: 0.838, 95% CI: 0.739-0.951) were protective factor for nicotine dependence. The sensitivity analysis showed consistent results.ConclusionThe Mendelian randomization study confirmed the causal link between genetically predicted risk of nicotine dependence and genetically predicted abundance of gut microbiota. Gut microbiota may serve as a biomarker and offer insights for addressing nicotine dependence.
| S-EPMC10664251 | biostudies-literature