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The causal relationship between gut microbiota and COVID-19: A two-sample Mendelian randomization analysis.

ABSTRACT: Recent studies have shown that gut microbiota is associated with coronavirus disease 2019 (COVID-19). However, the causal impact of the gut microbiota on COVID-19 remains unclear. We performed a bidirectional Mendelian randomization. The summary statistics on the gut microbiota from the MiBioGen consortium. Summary statistics for COVID-19 were obtained from the 6th round of the COVID-19 Host Genetics Initiative genome-wide association study meta-analysis. Inverse variance weighting was used as the main method to test the causal relationship between gut microbiota and COVID-19. Reverse Mendelian randomization analysis was performed. Mendelian randomization analysis showed that Intestinimas.id.2062 was associated with an increased risk of severe COVID-19. Bifidobacterium.id.436, LachnospiraceaeUCG010.id.11330, RikenellaceaeRC9gutgroup.id.11191 increase the risk of hospitalized COVID-19. RuminococcaceaeUCG014.id.11371 shows the positive protection on hospitalized COVID-19. There is no causal relationship between gut microbiota and infection with COVID-19. According to the results of reverse Mendelian randomization analysis, no significant causal effect of COVID-19 on gut microbiota was found. The study found that gut microbiota with COVID-19 has a causal relationship. This study provides a basis for the theory of the gut-lung axis. Further randomized controlled trials are needed to clarify the protective effect of probiotics against COVID-19 and the specific protective mechanisms. This study has important implications for gut microbiota as a nondrug intervention for COVID-19.

SUBMITTER: Tian S

PROVIDER: S-EPMC10843424 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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The causal relationship between gut microbiota and COVID-19: A two-sample Mendelian randomization analysis.

Tian Siyu S Huang Wenhui W

Medicine 20240201 5

Recent studies have shown that gut microbiota is associated with coronavirus disease 2019 (COVID-19). However, the causal impact of the gut microbiota on COVID-19 remains unclear. We performed a bidirectional Mendelian randomization. The summary statistics on the gut microbiota from the MiBioGen consortium. Summary statistics for COVID-19 were obtained from the 6th round of the COVID-19 Host Genetics Initiative genome-wide association study meta-analysis. Inverse variance weighting was used as t ...[more]

PMID: 38306556

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Project description:BackgroundThe interplay between gut microbiome genera and inflammatory kidney-related diseases, such as nephrotic syndrome, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease, has been observed. However, the causal relationships between specific bacterial genera and these renal diseases have not been fully elucidated.ObjectiveTo investigate the potential causal links between different genera of the gut microbiome and the susceptibility to various renal conditions utilizing two-sample Mendelian randomization (MR) analyses.Materials and methodsGenome-wide association study (GWAS) summary statistics of gut microbiota and inflammatory kidney-related diseases were obtained from published GWASs. Two-sample MR analyses were conducted using methods including inverse-variance weighted (IVW), MR Egger, and others to identify potential causal links between gut microbial genera and renal conditions. Sensitivity analyses, including Cochran's Q test and the MR-PRESSO global test, were performed to validate the robustness of the results and detect horizontal pleiotropy. In addition, a reverse MR analysis was conducted to assess reverse causation possibilities.ResultsBy synthesizing insights from both primary and sensitivity analyses, this study unveiled critical associations of 12 bacterial genera with nephrotic syndrome, 7 bacterial genera with membranous nephropathy, 3 bacterial genera with glomerulonephritis, 4 bacterial genera with acute tubulo-interstitial nephritis, 6 bacterial genera with chronic tubulo-interstitial nephritis, and 7 bacterial genera with chronic kidney disease. Various genera were pinpointed as having either positive or negative causal relationships with these renal conditions, as evidenced by specific ranges of IVW-OR values (all P< 0.05). The congruence of the sensitivity analyses bolstered the primary findings, displaying no marked heterogeneity or horizontal pleiotropy. Notably, the reverse MR analysis with nephritis as the exposure did not reveal any causal relationships, thereby strengthening the resilience and validity of the primary associations.ConclusionThis study explored the causal associations between several gut microbial genera and the risk of several inflammatory kidney-related diseases, uncovering several associations between specific gut microbial genera and nephrotic syndrome, membranous nephropathy, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease. These findings enhance our understanding of the complex interplay between the gut microbiome and kidney diseases, and they will be beneficial for early diagnosis and subsequent treatment.

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.

Project description:ObjectiveEmerging evidence has provided compelling evidence linking gut microbiota (GM) and diabetic nephropathy (DN) via the "gut-kidney" axis. But the causal relationship between them hasn't been clarified yet. We perform a Two-Sample Mendelian randomization (MR) analysis to reveal the causal connection with GM and the development of DN, type 1 diabetes nephropathy (T1DN), type 2 diabetes nephropathy (T2DN), type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM).MethodsWe used summary data from MiBioGen on 211 GM taxa in 18340 participants. Generalized MR analysis methods were conducted to estimate their causality on risk of DN, T1DN, T2DN, T1DM and T2DM from FinnGen. To ensure the reliability of the findings, a comprehensive set of sensitivity analyses were conducted to confirm the resilience and consistency of the results.ResultsIt was showed that Class Verrucomicrobiae [odds ratio (OR) =1.5651, 95%CI:1.1810-2.0742,PFDR=0.0018], Order Verrucomicrobiales (OR=1.5651, 95%CI: 1.1810-2.0742, PFDR=0.0018) and Family Verrucomicrobiaceae (OR=1.3956, 95%CI:1.0336-1.8844, PFDR=0.0296) had significant risk of DN. Our analysis found significant associations between GM and T2DN, including Class Verrucomimicrobiae (OR=1.8227, 95% CI: 1.2414-2.6763, PFDR=0.0139), Order Verrucomimicrobiae (OR=1.5651, 95% CI: 1.8227-2.6764, PFDR=0.0024), Rhodospirillales (OR=1.8226, 95% CI: 1.2412-2.6763, PFDR=0.0026), and Family Verrucomicroniaceae (OR=1.8226, 95% CI: 1.2412-2.6763, PFDR=0.0083). The Eubacteriumprotogenes (OR=0.4076, 95% CI: 0.2415-0.6882, PFDR=0.0021) exhibited a protection against T1DN. Sensitivity analyses confirmed that there was no significant heterogeneity and pleiotropy.ConclusionsAt the gene prediction level, we identified the specific GM that is causally linked to DN in both T1DM and T2DM patients. Moreover, we identified distinct microbial changes in T1DN that differed from those seen in T2DN, offering valuable insights into GM signatures associated with subtype of nephropathy.

Project description:BackgroundPrevious observational studies have provided cumulative data linking gut microbiota to myasthenia gravis (MG). However, the causal link between the two remains unexplored. Hence, the current study was performed to explore the causal link between them.MethodsMendelian randomization (MR) analysis was conducted using the summary statistics of 211 gut microbiota taxa and the largest genome-wide association studies (GWAS) for MG currently available. The inverse variance-weighted (IVW), MR-Egger, weighted median, and weighted mode methods were employed to ascertain the causal influence. Sensitivity studies utilizing several methodologies were then used to assess the robustness of the findings. Lastly, to evaluate reverse causality, a reverse MR analysis was performed.ResultsSeven suggestive causal associations between the gastrointestinal microbiota and MG were identified based on the outcomes of the MR analysis. Specifically, phylum Actinobacteria (OR: 0.602, 95% CI: 0.405-0.896, p = 0.012), class Gammaproteobacteria (OR: 0.587, 95% CI: 0.357-0.968, p = 0.037), and families Defluviitaleaceae (OR: 0.695, 95% CI: 0.485-0.996, p = 0.047), Family XIII (OR: 0.614, 95% CI: 0.412-0.916, p = 0.017), and Peptococcaceae (OR: 0.698, 95% CI: 0.505-0.964, p = 0.029) had suggestive protective effects on MG, while order Mollicutes RF9 (OR: 1.424, 95% CI: 1.015-1.998, p = 0.041) and genus Faecalibacterium (OR: 1.763, 95% CI: 1.220-2.547, p = 0.003) were suggestive risk factors for MG. The outcomes indicate that neither heterogeneity nor horizontal pleiotropy had any discernible impact. Nevertheless, this reverse analysis did not reveal any apparent effect of MG on the gut microbiota composition.ConclusionThe MR investigation has substantiated the suggestive causal connection between gut microbiota and MG, which may provide helpful insights for innovative therapeutic and preventative approaches for MG. Further randomized controlled trials are needed to elucidate the gut microbiota's precise role and therapeutic potential in the pathogenesis of MG.

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The causal relationship between gut microbiota and COVID-19: A two-sample Mendelian randomization analysis.

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The causal relationship between gut microbiota and COVID-19: A two-sample Mendelian randomization analysis.

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