Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris
BackgroundNumerous studies have suggested a correlation between gut microbiota and acne vulgaris; however, no specific causal link has been explored.Materials and methodsTo investigate the possible causal relationship between gut microbiota and acne vulgaris, this study employed a large-scale genome...
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| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1326339/full |
| _version_ | 1797334751206440960 |
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| author | Yujia Wu Xiaoyun Wang Wenjuan Wu Jiankang Yang |
| author_facet | Yujia Wu Xiaoyun Wang Wenjuan Wu Jiankang Yang |
| author_sort | Yujia Wu |
| collection | DOAJ |
| description | BackgroundNumerous studies have suggested a correlation between gut microbiota and acne vulgaris; however, no specific causal link has been explored.Materials and methodsTo investigate the possible causal relationship between gut microbiota and acne vulgaris, this study employed a large-scale genome-wide association study (GWAS) summary statistic. Initially, a two-sample Mendelian randomization (MR) analysis was utilized to identify the specific gut microflora responsible for acne vulgaris. We used the Inverse Variance Weighted (IVW) method as the main MR analysis method. Additionally, we assessed heterogeneity and horizontal pleiotropy, while also examining the potential influence of individual single-nucleotide polymorphisms (SNPs) on the analysis results. In order to eliminate gut microbiota with reverse causal associations, we conducted reverse MR analysis. Multivariate Mendelian randomization analysis (MVMR) was then employed to verify the independence of the causal associations. Finally, we performed SNP annotation on the instrumental variables of independent gut microbiota and acne vulgaris to determine the genes where these genetic variations are located. We also explored the biological functions of these genes through enrichment analysis.ResultThe IVW method of forward MR identified nine gut microbes with a causal relationship with acne vulgaris (p < 0.05). The findings from the sensitivity analysis demonstrate the absence of heterogeneity or horizontal pleiotropy, and leave-one-out analysis indicates that the results are not driven by a single SNP. Additionally, the Reverse MR analysis excluded two reverse-correlated pathogenic gut microbes. And then, MVMR was used to analyze seven gut microbes, and it was found that Cyanobacterium and Family XIII were risk factors for acne vulgaris, while Ruminococcus1 and Ruminiclostridium5 were protective factors for acne vulgaris. After conducting biological annotation, we identified six genes (PLA2G4A, FADS2, TIMP17, ADAMTS9, ZC3H3, and CPSF4L) that may be associated with the pathogenic gut microbiota of acne vulgaris patients. The enrichment analysis results indicate that PLA2G4A/FADS2 is associated with fatty acid metabolism pathways.ConclusionOur study found independent causal relationships between four gut microbes and acne vulgaris, and revealed a genetic association between acne vulgaris patients and gut microbiota. Consider preventing and treating acne vulgaris by interfering with the relative content of these four gut microbes. |
| first_indexed | 2024-03-08T08:25:43Z |
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| id | doaj.art-a8c67d6800c74861bafd710dda8a4df1 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-08T08:25:43Z |
| publishDate | 2024-02-01 |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-a8c67d6800c74861bafd710dda8a4df12024-02-02T04:44:00ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-02-011510.3389/fmicb.2024.13263391326339Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgarisYujia Wu0Xiaoyun Wang1Wenjuan Wu2Jiankang Yang3School of Basic Medical Sciences, Dali University, Dali, ChinaSchool of Basic Medical Sciences, Dali University, Dali, ChinaDepartment of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, ChinaSchool of Basic Medical Sciences, Dali University, Dali, ChinaBackgroundNumerous studies have suggested a correlation between gut microbiota and acne vulgaris; however, no specific causal link has been explored.Materials and methodsTo investigate the possible causal relationship between gut microbiota and acne vulgaris, this study employed a large-scale genome-wide association study (GWAS) summary statistic. Initially, a two-sample Mendelian randomization (MR) analysis was utilized to identify the specific gut microflora responsible for acne vulgaris. We used the Inverse Variance Weighted (IVW) method as the main MR analysis method. Additionally, we assessed heterogeneity and horizontal pleiotropy, while also examining the potential influence of individual single-nucleotide polymorphisms (SNPs) on the analysis results. In order to eliminate gut microbiota with reverse causal associations, we conducted reverse MR analysis. Multivariate Mendelian randomization analysis (MVMR) was then employed to verify the independence of the causal associations. Finally, we performed SNP annotation on the instrumental variables of independent gut microbiota and acne vulgaris to determine the genes where these genetic variations are located. We also explored the biological functions of these genes through enrichment analysis.ResultThe IVW method of forward MR identified nine gut microbes with a causal relationship with acne vulgaris (p < 0.05). The findings from the sensitivity analysis demonstrate the absence of heterogeneity or horizontal pleiotropy, and leave-one-out analysis indicates that the results are not driven by a single SNP. Additionally, the Reverse MR analysis excluded two reverse-correlated pathogenic gut microbes. And then, MVMR was used to analyze seven gut microbes, and it was found that Cyanobacterium and Family XIII were risk factors for acne vulgaris, while Ruminococcus1 and Ruminiclostridium5 were protective factors for acne vulgaris. After conducting biological annotation, we identified six genes (PLA2G4A, FADS2, TIMP17, ADAMTS9, ZC3H3, and CPSF4L) that may be associated with the pathogenic gut microbiota of acne vulgaris patients. The enrichment analysis results indicate that PLA2G4A/FADS2 is associated with fatty acid metabolism pathways.ConclusionOur study found independent causal relationships between four gut microbes and acne vulgaris, and revealed a genetic association between acne vulgaris patients and gut microbiota. Consider preventing and treating acne vulgaris by interfering with the relative content of these four gut microbes.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1326339/fullacne vulgarisgut microbiotaMendelian randomization analysisshort-chain fatty acidinflammation |
| spellingShingle | Yujia Wu Xiaoyun Wang Wenjuan Wu Jiankang Yang Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris Frontiers in Microbiology acne vulgaris gut microbiota Mendelian randomization analysis short-chain fatty acid inflammation |
| title | Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris |
| title_full | Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris |
| title_fullStr | Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris |
| title_full_unstemmed | Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris |
| title_short | Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris |
| title_sort | mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris |
| topic | acne vulgaris gut microbiota Mendelian randomization analysis short-chain fatty acid inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1326339/full |
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