Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study
Abstract Background Recent research has established the correlation between gut microbiota and periodontitis via oral-gut axis. Intestinal dysbiosis may play a pivotal bridging role in extra-oral inflammatory comorbidities caused by periodontitis. However, it is unclear whether the link is merely co...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-023-04559-9 |
| _version_ | 1797451706369310720 |
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| author | Xinjian Ye Bin Liu Yijing Bai Yue Cao Sirui Lin Linshuoshuo Lyu Haohao Meng Yuwei Dai Ding Ye Weiyi Pan Zhiyong Wang Yingying Mao Qianming Chen |
| author_facet | Xinjian Ye Bin Liu Yijing Bai Yue Cao Sirui Lin Linshuoshuo Lyu Haohao Meng Yuwei Dai Ding Ye Weiyi Pan Zhiyong Wang Yingying Mao Qianming Chen |
| author_sort | Xinjian Ye |
| collection | DOAJ |
| description | Abstract Background Recent research has established the correlation between gut microbiota and periodontitis via oral-gut axis. Intestinal dysbiosis may play a pivotal bridging role in extra-oral inflammatory comorbidities caused by periodontitis. However, it is unclear whether the link is merely correlative or orchestrated by causative mechanistic interactions. This two-sample Mendelian randomization (MR) study was performed to evaluate the potential bidirectional causal relationships between gut microbiota and periodontitis. Materials and Methods A two-sample MR analysis was performed using summary statistics from genome-wide association studies (GWAS) for gut microbiota (n = 18,340) and periodontitis (cases = 12,251; controls = 22,845). The inverse-variance weighted (IVW) method was used for the primary analysis, and we employed sensitivity analyses to assess the robustness of the main results. The PhenoScanner database was then searched for pleiotropy SNPs associated with potential confounders. In order to identify the possibly influential SNPs, we further conducted the leave-one-out analysis. Finally, a reverse MR analysis was performed to evaluate the possibility of links between periodontitis and genetically predicted gut microbiota alternation. Results 2,699 single nucleotide polymorphisms (SNPs) associated with 196 microbiota genera were selected as instrumental variables (IVs). IVW method suggested that order Enterobacteriales (OR: 1.35, 95% CI 1.10–1.66), family Bacteroidales S24.7group (OR: 1.22, 95% CI 1.05–1.41), genus Lachnospiraceae UCG008 (OR: 1.16, 95% CI 1.03–1.31), genus Prevotella 7 (OR: 1.11, 95% CI 1.01–1.23), and order Pasteurellales (OR: 1.12, 95% CI 1.00–1.26) may be associated with a higher risk of periodontitis, while genus Ruminiclostridium 6 may be linked to a lower risk (OR: 0.82, 95% CI 0.70–0.95). The sensitivity and heterogeneity analyses yielded no indication of horizontal pleiotropy or heterogeneity. Only the association between order Enterobacteriales and the likelihood of periodontitis remained consistent across all alternative MR approaches. In the reverse MR analysis, four microbiota genera were genetically predicted to be down-regulated in periodontitis, whereas two were predicted to be up-regulated. Conclusions The present MR analysis demonstrated the potential bidirectional causal relationships between gut microbiota and periodontitis. Our research provided fresh insights for the prevention and management of periodontitis. Future research is required to support the finding of our current study. |
| first_indexed | 2024-03-09T14:58:23Z |
| format | Article |
| id | doaj.art-b1357b28b8c44e8bbfa609155a742e47 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-09T14:58:23Z |
| publishDate | 2023-09-01 |
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| series | Journal of Translational Medicine |
| spelling | doaj.art-b1357b28b8c44e8bbfa609155a742e472023-11-26T14:04:22ZengBMCJournal of Translational Medicine1479-58762023-09-0121111110.1186/s12967-023-04559-9Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization studyXinjian Ye0Bin Liu1Yijing Bai2Yue Cao3Sirui Lin4Linshuoshuo Lyu5Haohao Meng6Yuwei Dai7Ding Ye8Weiyi Pan9Zhiyong Wang10Yingying Mao11Qianming Chen12School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Stomatology Hospital, Cancer Center of Zhejiang UniversityDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical UniversityThe First School of Clinical Medicine, Zhejiang Chinese Medical UniversitySchool of Stomatology, Zhejiang Chinese Medical UniversityDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical UniversityDepartment of Environmental Health Sciences, Yale School of Public HealthSchool of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Stomatology Hospital, Cancer Center of Zhejiang UniversitySchool of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Stomatology Hospital, Cancer Center of Zhejiang UniversityDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical UniversitySchool of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Stomatology Hospital, Cancer Center of Zhejiang UniversitySchool of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Stomatology Hospital, Cancer Center of Zhejiang UniversityDepartment of Epidemiology, School of Public Health, Zhejiang Chinese Medical UniversitySchool of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Stomatology Hospital, Cancer Center of Zhejiang UniversityAbstract Background Recent research has established the correlation between gut microbiota and periodontitis via oral-gut axis. Intestinal dysbiosis may play a pivotal bridging role in extra-oral inflammatory comorbidities caused by periodontitis. However, it is unclear whether the link is merely correlative or orchestrated by causative mechanistic interactions. This two-sample Mendelian randomization (MR) study was performed to evaluate the potential bidirectional causal relationships between gut microbiota and periodontitis. Materials and Methods A two-sample MR analysis was performed using summary statistics from genome-wide association studies (GWAS) for gut microbiota (n = 18,340) and periodontitis (cases = 12,251; controls = 22,845). The inverse-variance weighted (IVW) method was used for the primary analysis, and we employed sensitivity analyses to assess the robustness of the main results. The PhenoScanner database was then searched for pleiotropy SNPs associated with potential confounders. In order to identify the possibly influential SNPs, we further conducted the leave-one-out analysis. Finally, a reverse MR analysis was performed to evaluate the possibility of links between periodontitis and genetically predicted gut microbiota alternation. Results 2,699 single nucleotide polymorphisms (SNPs) associated with 196 microbiota genera were selected as instrumental variables (IVs). IVW method suggested that order Enterobacteriales (OR: 1.35, 95% CI 1.10–1.66), family Bacteroidales S24.7group (OR: 1.22, 95% CI 1.05–1.41), genus Lachnospiraceae UCG008 (OR: 1.16, 95% CI 1.03–1.31), genus Prevotella 7 (OR: 1.11, 95% CI 1.01–1.23), and order Pasteurellales (OR: 1.12, 95% CI 1.00–1.26) may be associated with a higher risk of periodontitis, while genus Ruminiclostridium 6 may be linked to a lower risk (OR: 0.82, 95% CI 0.70–0.95). The sensitivity and heterogeneity analyses yielded no indication of horizontal pleiotropy or heterogeneity. Only the association between order Enterobacteriales and the likelihood of periodontitis remained consistent across all alternative MR approaches. In the reverse MR analysis, four microbiota genera were genetically predicted to be down-regulated in periodontitis, whereas two were predicted to be up-regulated. Conclusions The present MR analysis demonstrated the potential bidirectional causal relationships between gut microbiota and periodontitis. Our research provided fresh insights for the prevention and management of periodontitis. Future research is required to support the finding of our current study.https://doi.org/10.1186/s12967-023-04559-9Gut microbiotaPeriodontitisMendelian randomizationOral-gut axisExtra-oral inflammatory comorbidityProbiotics |
| spellingShingle | Xinjian Ye Bin Liu Yijing Bai Yue Cao Sirui Lin Linshuoshuo Lyu Haohao Meng Yuwei Dai Ding Ye Weiyi Pan Zhiyong Wang Yingying Mao Qianming Chen Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study Journal of Translational Medicine Gut microbiota Periodontitis Mendelian randomization Oral-gut axis Extra-oral inflammatory comorbidity Probiotics |
| title | Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study |
| title_full | Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study |
| title_fullStr | Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study |
| title_full_unstemmed | Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study |
| title_short | Genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis: insights from a two-sample Mendelian randomization study |
| title_sort | genetic evidence strengthens the bidirectional connection between gut microbiota and periodontitis insights from a two sample mendelian randomization study |
| topic | Gut microbiota Periodontitis Mendelian randomization Oral-gut axis Extra-oral inflammatory comorbidity Probiotics |
| url | https://doi.org/10.1186/s12967-023-04559-9 |
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