Dataset Information

Causal effects of gut microbiome on hypertension: a Mendelian randomization study.

ABSTRACT:

Background

Previous observational studies have shown that there is an important relationship between gut microbiota and hypertension, we performed a two-sample Mendelian randomization analysis to examine whether the gut microbiota is causally related to hypertension in order to find a basis for potential diagnostic or intervention approaches for hypertension.

Methods

We obtained significant single nucleotide polymorphisms related to gut microbiota and hypertension from publicly available genome-wide association studies for a two-sample Mendelian randomization study. A total of 18,340 individual genome-wide genotype data were included from 24 population-based cohorts. The inverse-variance weighted meta-analysis is the main analytical method for evaluating causal relationships, and the Mendelian randomization research results have been validated through a series of sensitivity analyses.

Results

The inverse-variance weighted analysis results indicated that phylum Verrucomicrobia (OR:0.831, 95%CI: 0.710-0.972; p = 0.021), family BacteroidalesS24.7group (OR:0.672, 95%CI: 0.496-0.911; p = 0.01), family Bifidobacteriaceae (OR:0.709, 95%CI:0.569-0.884, p = 0.002), genus Adlercreutzia (OR: 0.991, 95%CI: 0.982-0.999, p = 0.035), genus Phascolarctacterium (OR:0.819, 95%CI:0.685-0.981; p = 0.03), genus LachnospiraceaeNK4A136group (OR:0.990, 95%CI:0.981-0.999; p = 0.025), and genus Ruminococcus2 (OR:0.988, 95%CI: 0.979-0.997; p = 0.008) had protective causal effects on hypertension. The Family Alcaliginaceae (OR:1.011, 95%CI:1.000-1.021, p = 0.04), Genus Anaerostipes (OR:1.375, 95%CI:1.096-1.653; p = 0.025), Genus Collinsella (OR:1.899, 95%CI:1.361-2.348; p = 0.02), and Genus Lachnospiraceae_UCG_010 (OR:1.536, 95%CI:1.072-2.202; p = 0.019) were associated with a higher risk of HTN. The reverse Mendelian randomization analysis results showed no reverse causal relationship between HTN and these bacterial taxa.

Conclusion

Our Mendelian randomization analysis results indicate a potential causal relationship between these bacterial taxa and hypertension, providing a new perspective for the treatment and prevention of hypertension.

SUBMITTER: He G

PROVIDER: S-EPMC10712025 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Causal effects of gut microbiome on hypertension: a Mendelian randomization study.

He Gang G Cao Yu Y Wang Houzhao H Lv Xiaoying X

Frontiers in microbiology 20231123

<h4>Background</h4>Previous observational studies have shown that there is an important relationship between gut microbiota and hypertension, we performed a two-sample Mendelian randomization analysis to examine whether the gut microbiota is causally related to hypertension in order to find a basis for potential diagnostic or intervention approaches for hypertension.<h4>Methods</h4>We obtained significant single nucleotide polymorphisms related to gut microbiota and hypertension from publicly av ...[more]

PMID: 38088967

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Project description:BackgroundObservational studies have shown gut microbiomes were associated with cardiovascular diseases (CVDs), but their roles remain controversial, and these associations have not yet been established causally.MethodsTwo-sample Mendelian randomization (MR) was used to investigate whether gut microbiome had a causal effect on the risk of CVDs. To obtain comprehensive results, we performed two sets of MR analyses, one with single nucleotide polymorphisms (SNPs) that smaller than the genome-wide statistical significance threshold (5 × 10-8) as instrumental variables, and the other with SNPs that lower than the locus-wide significance level (1 × 10-5). Summary-level statistics for CVDs, including coronary artery disease (CAD), myocardial infarction, heart failure, atrial fibrillation, stroke and its subtypes were collected. The ME estimation was performed using the inverse-variance weighted and Wald ratio methods. Sensitivity analysis was performed using the weighted median, MR-Egger, leave-one-out analysis, MR pleiotropy residual sum and outlier and MR Steiger.ResultsBased on the locus-wide significance level, genetically predicted genus Oxalobacter was positively associated with the risk of CAD (odds ratio (OR) = 1.06, 95% confidence interval (CI), 1.03 - 1.10, P = 1.67 × 10-4), family Clostridiaceae_1 was negatively correlated with stroke risk (OR = 0.83,95% CI, 0.75-0.93, P = 7.76 × 10-4) and ischemic stroke risk (OR = 0.823,95% CI, 0.74-0.92, P = 4.15 × 10-4). There was no causal relationship between other genetically predicted gut microbiome components and CVDs risk. Based on the genome-wide statistical significance threshold, the results showed that the gut microbiome had no causal relationship with CVDs risk.ConclusionOur findings reveal that there are beneficial or adverse causal effects of gut microbiome components on CVDs risk and provide novel insights into strategies for the prevention and management of CVDs through the gut microbiome.

Project description:Background & aimsThe pathogenesis of hypertension involves a diverse range of genetic, environmental, hemodynamic, and more causative factors. Recent evidence points to an association between the gut microbiome and hypertension. Given that the microbiota is in part determined by host genetics, we used the two-sample Mendelian randomization (MR) analysis to address the bidirectional causal link between gut microbiota and hypertension.MethodsWe selected genetic variants (P < 1 × 10-5) for gut microbiota (n = 18,340) from the MiBioGen study. Genetic association estimates for hypertension were extracted from genome-wide association study (GWAS) summary statistics on 54,358 cases and 408,652 controls. Seven complementary MR methods were implemented, including the inverse-variance weighted (IVW) method, followed by sensitivity analyses to verify the robustness of the results. Reverse-direction MR analyses were further conducted to probe if there was a reverse causative relationship. Bidirectional MR analysis then examines a modulation of gut microbiota composition by hypertension.ResultsAt the genus level, our MR estimates from gut microbiome to hypertension showed that there were 5 protective factors Allisonella, Parabacteroide, Phascolarctobacterium, Senegalimassilia, and unknowngenus (id.1000000073), while 6 genera Clostridiuminnocuum, Eubacteriumcoprostanoligenes, Eubacteriumfissicatena, Anaerostipes, LachnospiraceaeFCS020, and unknowngenus (id.2041) are risk factors. The Alcaligenaceae and ClostridialesvadinBB60 were detrimental and beneficial at the family level, respectively. In contrast, the MR results of hypertension-gut flora showed hypertensive states can lead to an increased abundance of Eubacteriumxylanophilum, Eisenbergiella, and Lachnospiraceae and a lower abundance of Alistipes, Bilophila, Butyricimonas, and Phascolarctobacterium.ConclusionAltered gut microbiota is a causal factor in the development of hypertension, and hypertension causes imbalances in the intestinal flora. Substantial research is still needed to find the key gut flora and explore the specific mechanisms of their effects so that new biomarkers can be found for blood pressure control.

Project description:BackgroundThe causal association between gut microbiome and HIV infection remains to be elucidated. We conducted a two-sample mendelian randomization analysis to estimate the causality between gut microbiome and HIV infection.MethodsPublicly released genome-wide association studies summary data were collected to perform the mendelian analysis. The GWAS summary data of gut microbiome was retrieved from the MiBioGen consortium, which contains 18 340 samples from 24 cohorts. GWAS summary data of HIV infection was collected from the R5 release of FinnGen consortium, including 357 HIV infected cases and 218 435 controls. The SNPs were selected as instrumental variables according to our selection rules. And SNPs with a F-statistics less than ten were regarded as weak instrumental variables and excluded. Mendelian randomization analysis was conducted by five methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. The Cochran's Q test and MR-Egger intercept test were performed to identify heterogeneity and pleiotropy. Leave-one-out analysis were used to test the sensitivity of the results.ResultsFifteen gut microbiota taxa showed causal effects on HIV infection according to the MR methods. Four taxa were observed to increase the risk of HIV infection, including Ruminococcaceae (OR: 2.468[1.043, 5.842], P: 0.039), Ruminococcaceae UCG005 (OR: 2.051[1.048, 4.011], P: 0.036), Subdoligranulum (OR: 3.957[1.762, 8.887], P < 0.001) and Victivallis (OR: 1.605[1.012, 2.547], P=0.044). Erysipelotrichaceae was protective factor of HIV infection (OR: 0.278[0.106, 0.731], P < 0.001) and Methanobrevibacter was also found to be associated with reduced risk of HIV infection (OR: 0.509[0.265, 0.980], P=0.043). Horizontal pleiotropy was found for Fusicatenibacter (P<0.05) according to the MR-Egger regression intercept analysis. No heterogeneity was detected.ConclusionOur results demonstrate significant causal effects of gut microbiome on HIV infection. These findings facilitate future studies to develop better strategies for HIV prophylaxis through gut microbiome regulation. Further explorations are also warranted to dissect the mechanism of how gut microbiome affects HIV susceptibility.

Dataset Information

Causal effects of gut microbiome on hypertension: a Mendelian randomization study.

Background

Methods

Results

Conclusion

Publications

Causal effects of gut microbiome on hypertension: a Mendelian randomization study.

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