Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study
IntroductionThis study explored the causal connections between gut microbiota (GM), urinary tract infection (UTI), and potential metabolite mediators using Mendelian randomization (MR).MethodsWe utilized summary statistics from the most comprehensive and extensive genome-wide association studies (GW...
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1384095/full |
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| author | Yining He Yining He Chao Han Chao Han Chengjuan Li Chengjuan Li Xiaofan Yin Xiaofan Yin Jiawen Wang Jiawen Wang Lina Gu Lina Gu Ruxue Yan Ruxue Yan Buhui Liu Xuan Zhou Weiming He |
| author_facet | Yining He Yining He Chao Han Chao Han Chengjuan Li Chengjuan Li Xiaofan Yin Xiaofan Yin Jiawen Wang Jiawen Wang Lina Gu Lina Gu Ruxue Yan Ruxue Yan Buhui Liu Xuan Zhou Weiming He |
| author_sort | Yining He |
| collection | DOAJ |
| description | IntroductionThis study explored the causal connections between gut microbiota (GM), urinary tract infection (UTI), and potential metabolite mediators using Mendelian randomization (MR).MethodsWe utilized summary statistics from the most comprehensive and extensive genome-wide association studies (GWAS) available to date, including 196 bacterial traits for GM, 1,091 blood metabolites, 309 metabolite ratios, alongside UTI data from ukb-b-8814 and ebi-a-GCST90013890. Bidirectional MR analyses were conducted to investigate the causal links between GM and UTI. Subsequently, two MR analyses were performed to identify the potential mediating metabolites, followed by a two-step MR analysis to quantify the mediation proportion.ResultsOur findings revealed that out of the total 15 bacterial traits, significant associations with UTI risk were observed across both datasets. Particularly, taxon g_Ruminococcaceae UCG010 displayed a causal link with a diminished UTI risk in both datasets (ukb-b-8814: odds ratio [OR] = 0.9964, 95% confidence interval [CI] = 0.9930–0.9997, P = 0.036; GCST90013890: OR = 0.8252, 95% CI = 0.7217–0.9436, P = 0.005). However, no substantial changes in g_Ruminococcaceae UCG010 due to UTI were noted (ukb-b-8814: β = 0.51, P = 0.87; ebi-a-GCST90013890: β = −0.02, P = 0.77). Additionally, variations in 56 specific metabolites were induced by g_Ruminococcaceae UCG010, with N-acetylkynurenine (NAK) exhibiting a causal correlation with UTI. A negative association was found between g_Ruminococcaceae UCG010 and NAK (OR: 0.8128, 95% CI: 0.6647–0.9941, P = 0.044), while NAK was positively associated with UTI risk (OR: 1.0009; 95% CI: 1.0002–1.0016; P = 0.0173). Mediation analysis revealed that the association between g_Ruminococcaceae UCG010 and UTI was mediated by NAK with a mediation proportion of 5.07%.DiscussionThis MR study provides compelling evidence supporting the existence of causal relationships between specific GM taxa and UTI, along with potential mediating metabolites. |
| first_indexed | 2024-04-24T07:04:39Z |
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| last_indexed | 2024-04-24T07:04:39Z |
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| spelling | doaj.art-bdaf6927186045d2a5a74a826c5b1fe02024-04-22T04:57:14ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-04-011510.3389/fmicb.2024.13840951384095Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization studyYining He0Yining He1Chao Han2Chao Han3Chengjuan Li4Chengjuan Li5Xiaofan Yin6Xiaofan Yin7Jiawen Wang8Jiawen Wang9Lina Gu10Lina Gu11Ruxue Yan12Ruxue Yan13Buhui Liu14Xuan Zhou15Weiming He16The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDivision of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaThe First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaYancheng Dafeng Hospital of Chinese Medicine, Teaching Hospital of Nanjing University of Chinese Medicine, Yancheng, ChinaThe First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDivision of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaThe First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDivision of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaThe First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDivision of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaThe First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDivision of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaThe First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDivision of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaDepartment of Human Anatomy, Xuzhou Medical University, Xuzhou, ChinaDepartment of Respiratory, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDivision of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, ChinaIntroductionThis study explored the causal connections between gut microbiota (GM), urinary tract infection (UTI), and potential metabolite mediators using Mendelian randomization (MR).MethodsWe utilized summary statistics from the most comprehensive and extensive genome-wide association studies (GWAS) available to date, including 196 bacterial traits for GM, 1,091 blood metabolites, 309 metabolite ratios, alongside UTI data from ukb-b-8814 and ebi-a-GCST90013890. Bidirectional MR analyses were conducted to investigate the causal links between GM and UTI. Subsequently, two MR analyses were performed to identify the potential mediating metabolites, followed by a two-step MR analysis to quantify the mediation proportion.ResultsOur findings revealed that out of the total 15 bacterial traits, significant associations with UTI risk were observed across both datasets. Particularly, taxon g_Ruminococcaceae UCG010 displayed a causal link with a diminished UTI risk in both datasets (ukb-b-8814: odds ratio [OR] = 0.9964, 95% confidence interval [CI] = 0.9930–0.9997, P = 0.036; GCST90013890: OR = 0.8252, 95% CI = 0.7217–0.9436, P = 0.005). However, no substantial changes in g_Ruminococcaceae UCG010 due to UTI were noted (ukb-b-8814: β = 0.51, P = 0.87; ebi-a-GCST90013890: β = −0.02, P = 0.77). Additionally, variations in 56 specific metabolites were induced by g_Ruminococcaceae UCG010, with N-acetylkynurenine (NAK) exhibiting a causal correlation with UTI. A negative association was found between g_Ruminococcaceae UCG010 and NAK (OR: 0.8128, 95% CI: 0.6647–0.9941, P = 0.044), while NAK was positively associated with UTI risk (OR: 1.0009; 95% CI: 1.0002–1.0016; P = 0.0173). Mediation analysis revealed that the association between g_Ruminococcaceae UCG010 and UTI was mediated by NAK with a mediation proportion of 5.07%.DiscussionThis MR study provides compelling evidence supporting the existence of causal relationships between specific GM taxa and UTI, along with potential mediating metabolites.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1384095/fullgut microbiotaurinary tract infectionblood metabolitesN-acetylkynurenineMendelian randomization analysis |
| spellingShingle | Yining He Yining He Chao Han Chao Han Chengjuan Li Chengjuan Li Xiaofan Yin Xiaofan Yin Jiawen Wang Jiawen Wang Lina Gu Lina Gu Ruxue Yan Ruxue Yan Buhui Liu Xuan Zhou Weiming He Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study Frontiers in Microbiology gut microbiota urinary tract infection blood metabolites N-acetylkynurenine Mendelian randomization analysis |
| title | Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study |
| title_full | Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study |
| title_fullStr | Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study |
| title_full_unstemmed | Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study |
| title_short | Role of N-acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection: a Mendelian randomization study |
| title_sort | role of n acetylkynurenine in mediating the effect of gut microbiota on urinary tract infection a mendelian randomization study |
| topic | gut microbiota urinary tract infection blood metabolites N-acetylkynurenine Mendelian randomization analysis |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1384095/full |
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