Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization

Hou, Tianzhichao; Dai, Huajie; Wang, Qi; Hou, Yanan; Zhang, Xiaoyun; Lin, Hong; Wang, Shuangyuan; Li, Mian; Zhao, Zhiyun; Lu, Jieli; Xu, Yu; Chen, Yuhong; Gu, Yuchao; Zheng, Jie; Wang, Tiange; Wang, Weiqing; Bi, Yufang; Ning, Guang; Xu, Min

doi:10.3389/fimmu.2023.1148591

Cited by 12 publications

(7 citation statements)

References 55 publications

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“…Due to differences in data, such as the inclusion of different participants, the other researchers have also found that Escherichia Shigella, Lachnospiraceae NC2004 group, Family XIII AD3011 group, Coprococcus 3, Bifidobacteriales order and Bifidobacteriaceae family are closely related to gout. 67,68 These findings could be mutually complementary with our results.…”

Section: Discussionsupporting

confidence: 90%

Investigating the Impact of Gut Microbiota on Gout Through Mendelian Randomization

Tang,

Li,

Jin

et al. 2024

ORR

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Background:The relationship between gout and gut microbiota has attracted significant attention in current research. However, due to the diverse range of gut microbiota, the specific causal effect on gout remains unclear. This study utilizes Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and gout, aiming to elucidate the underlying mechanism of microbiome-mediated gout and provide valuable guidance for clinical prevention and treatment. Materials and Methods: The largest genome-wide association study meta-analysis conducted by the MiBioGen Consortium (n=18,340) was utilized to perform a two-sample Mendelian randomization investigation on aggregate statistics of intestinal microbiota. Summary statistics for gout were utilized from the data released by EBI. Various methods, including inverse variance weighted, weighted median, weighted model, MR-Egger, and Simple-mode, were employed to assess the causal relationship between gut microbiota and gout. Reverse Mendelian randomization analysis revealed a causal association between bacteria and gout in forward Mendelian randomization analysis. Cochran's Q statistic was used to quantify instrumental variable heterogeneity. Results: The inverse variance weighted estimation revealed that Rikenellaceae exhibited a slight protective effect on gout, while the presence of Ruminococcaceae UCG_011 is associated with a marginal increase in the risk of gout. According to the reverse Mendelian Randomization results, no significant causal relationship between gout and gut microbiota was observed. No significant heterogeneity of instrumental variables or level pleiotropy was detected. Conclusion:Our MR analysis revealed a potential causal relationship between the development of gout and specific gut microbiota; however, the causal effect was not robust, and further research is warranted to elucidate its underlying mechanism in gout development. Considering the significant association between diet, gut microbiota, and gout, these findings undoubtedly shed light on the mechanisms of microbiota-mediated gout and provide new insights for translational research on managing and standardizing treatment for this condition.

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Section: Discussionsupporting

confidence: 90%

Investigating the Impact of Gut Microbiota on Gout Through Mendelian Randomization

Tang,

Li,

Jin

et al. 2024

ORR

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“…The process of selecting instrumental variables (IVs) for exposure in MR adhered to certain guidelines [ 40 ]. For every microbiota taxon and pathway, variants that exhibited a genome-wide significance level of p < 1 × 10 −5 and effect allele frequency (EAF) of >0.01 were included [ 41 ]. These genetic variants were subjected to a clumping process using a linkage disequilibrium threshold of r 2 < 0.001 by leveraging the 1000 Genomes European reference panel.…”

Section: Methodsmentioning

confidence: 99%

Causal Link between Gut Microbiota, Neurophysiological States, and Bone Diseases: A Comprehensive Mendelian Randomization Study

Luo,

Chen,

Deng

et al. 2023

Nutrients

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Increasing evidence highlights a robust correlation between the gut microbiota and bone diseases; however, the existence of a causal relationship between them remains unclear. In this study, we thoroughly examined the correlation between gut microbiota and skeletal diseases using genome-wide association studies. Linkage disequilibrium score regression and Mendelian randomization were used to probe genetic causality. Furthermore, the potential mediating role of neuropsychological states (i.e., cognition, depression, and insomnia) between the gut microbiota and bone diseases was evaluated using mediation analysis, with genetic colocalization analysis revealing potential targets. These findings suggest a direct causal relationship between Ruminococcaceae and knee osteoarthritis (OA), which appears to be mediated by cognitive performance and insomnia. Similarly, a causal association was observed between Burkholderiales and lumbar pelvic fractures, mediated by cognitive performance. Colocalization analysis identified a shared causal variant (rs2352974) at the TRAF-interacting protein locus for cognitive ability and knee OA. This study provides compelling evidence that alterations in the gut microbiota can enhance cognitive ability, ameliorate insomnia, and potentially reduce the risk of site-specific fractures and OA. Therefore, strategies targeting gut microbiota optimization could serve as novel and effective preventive measures against fractures and OA.

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“…Heterogeneity was estimated by Cochran’s Q statistic, and the results with the P-value < 0.05 were removed due to their heterogeneity. Furthermore, we conduct The Mendelian Randomization Pleiotropy Residual Sum and Outlier(MR-PRESSO) tests to assess horizontal pleiotropy [ 35 ], and the MR Steiger test to ensure the right causal direction from exposure to outcome [ 36 ]. The Benjamini‒Hochberg method was used to evaluate the false discovery rate(FDR) and provided corrected FDR Q-value [ 37 ], which methods have been widely performed in this field.…”

Section: Methodsmentioning

confidence: 99%

Investigating the causal relationship of gut microbiota with GERD and BE: a bidirectional mendelian randomization

Liu,

Yu,

Yang

et al. 2024

BMC Genomics

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Background Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett’s esophagus(BE) hasn’t been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis. Methods Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE. Results 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01–1.17) and BE(OR = 1.388, 95%CI = 1.03–1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways. Conclusions This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.

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Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization

Cited by 12 publications

References 55 publications

Investigating the Impact of Gut Microbiota on Gout Through Mendelian Randomization

Investigating the Impact of Gut Microbiota on Gout Through Mendelian Randomization

Causal Link between Gut Microbiota, Neurophysiological States, and Bone Diseases: A Comprehensive Mendelian Randomization Study

Investigating the causal relationship of gut microbiota with GERD and BE: a bidirectional mendelian randomization

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