The Causal Relationship Between Gut Microbiomes, Inflammatory Mediators, and Traumatic Brain Injury in Europeans: Evidence from Genetic Correlation and Functional Mapping Annotation Analyses
<b>Background:</b> The gut microbiome (GM) has been reported to play a role in traumatic brain injury (TBI). To investigate the causal relationship between GMs, inflammatory mediators, and TBI, a comprehensive Mendelian randomization (MR) analysis was conducted. <b>Methods:</b&g...
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2025-03-01
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| author | Bingyi Song Youjia Qiu Zilan Wang Yuchen Tao Menghan Wang Aojie Duan Minjia Xie Ziqian Yin Zhouqing Chen Chao Ma Zhong Wang |
| author_facet | Bingyi Song Youjia Qiu Zilan Wang Yuchen Tao Menghan Wang Aojie Duan Minjia Xie Ziqian Yin Zhouqing Chen Chao Ma Zhong Wang |
| author_sort | Bingyi Song |
| collection | DOAJ |
| description | <b>Background:</b> The gut microbiome (GM) has been reported to play a role in traumatic brain injury (TBI). To investigate the causal relationship between GMs, inflammatory mediators, and TBI, a comprehensive Mendelian randomization (MR) analysis was conducted. <b>Methods:</b> We utilized Genome-Wide Association Study (GWAS) summary statistics to examine the causal relationships between GM and TBI. To assess the potential causal associations between GM and TBI, we employed the inverse-variance-weighted, MR-Egger, and weighted median methods. Mediation analysis was used to assess the possible mediating factors. Several sensitivity analyses methods were implemented to verify the stability of the results. Additionally, we utilized FUMA GWAS to map single-nucleotide polymorphisms to genes and conduct transcriptomic MR analysis. <b>Results:</b> We identified potential causal relationships between nine bacterial taxa and TBI. Notably, class <i>Methanobacteria</i>, family <i>Methanobacteriaceae</i>, and order <i>Methanobacteriales</i> (<i>p</i> = 0.0003) maintained a robust positive correlation with TBI. This causal association passed false discovery rate (FDR) correction (FDR < 0.05). Genetically determined 1 inflammatory protein, 30 immune cells and 3 inflammatory factors were significantly causally related to TBI. None of them mediated the relationship between GMs and TBI. The outcome of the sensitivity analysis corroborated the findings. Regarding the mapped genes of significant GMs, genes such as <i>CLK4</i>, <i>MTRF1</i>, <i>NAA16</i>, <i>SH3BP5</i>, and <i>ZNF354A</i> in class <i>Methanobacteria</i> showed a significant causal correlation with TBI. <b>Conclusions:</b> Our study reveals the potential causal effects of nine GMs, especially <i>Methanogens</i> on TBI, and there was no link between TBI and GM through inflammatory protein, immune cells, and inflammatory factors, which may offer fresh insights into TBI biomarkers and therapeutic targets through specific GMs. |
| format | Article |
| id | doaj-art-488694bc762a44edbabf2aa03bd301ad |
| institution | DOAJ |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-488694bc762a44edbabf2aa03bd301ad2025-08-20T02:42:42ZengMDPI AGBiomedicines2227-90592025-03-0113375310.3390/biomedicines13030753The Causal Relationship Between Gut Microbiomes, Inflammatory Mediators, and Traumatic Brain Injury in Europeans: Evidence from Genetic Correlation and Functional Mapping Annotation AnalysesBingyi Song0Youjia Qiu1Zilan Wang2Yuchen Tao3Menghan Wang4Aojie Duan5Minjia Xie6Ziqian Yin7Zhouqing Chen8Chao Ma9Zhong Wang10Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaSuzhou Medical College, Soochow University, Suzhou 215002, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China<b>Background:</b> The gut microbiome (GM) has been reported to play a role in traumatic brain injury (TBI). To investigate the causal relationship between GMs, inflammatory mediators, and TBI, a comprehensive Mendelian randomization (MR) analysis was conducted. <b>Methods:</b> We utilized Genome-Wide Association Study (GWAS) summary statistics to examine the causal relationships between GM and TBI. To assess the potential causal associations between GM and TBI, we employed the inverse-variance-weighted, MR-Egger, and weighted median methods. Mediation analysis was used to assess the possible mediating factors. Several sensitivity analyses methods were implemented to verify the stability of the results. Additionally, we utilized FUMA GWAS to map single-nucleotide polymorphisms to genes and conduct transcriptomic MR analysis. <b>Results:</b> We identified potential causal relationships between nine bacterial taxa and TBI. Notably, class <i>Methanobacteria</i>, family <i>Methanobacteriaceae</i>, and order <i>Methanobacteriales</i> (<i>p</i> = 0.0003) maintained a robust positive correlation with TBI. This causal association passed false discovery rate (FDR) correction (FDR < 0.05). Genetically determined 1 inflammatory protein, 30 immune cells and 3 inflammatory factors were significantly causally related to TBI. None of them mediated the relationship between GMs and TBI. The outcome of the sensitivity analysis corroborated the findings. Regarding the mapped genes of significant GMs, genes such as <i>CLK4</i>, <i>MTRF1</i>, <i>NAA16</i>, <i>SH3BP5</i>, and <i>ZNF354A</i> in class <i>Methanobacteria</i> showed a significant causal correlation with TBI. <b>Conclusions:</b> Our study reveals the potential causal effects of nine GMs, especially <i>Methanogens</i> on TBI, and there was no link between TBI and GM through inflammatory protein, immune cells, and inflammatory factors, which may offer fresh insights into TBI biomarkers and therapeutic targets through specific GMs.https://www.mdpi.com/2227-9059/13/3/753gut microbiometraumatic brain injurymendelian randomizationinflammatory factorimmune cellmapped genes |
| spellingShingle | Bingyi Song Youjia Qiu Zilan Wang Yuchen Tao Menghan Wang Aojie Duan Minjia Xie Ziqian Yin Zhouqing Chen Chao Ma Zhong Wang The Causal Relationship Between Gut Microbiomes, Inflammatory Mediators, and Traumatic Brain Injury in Europeans: Evidence from Genetic Correlation and Functional Mapping Annotation Analyses Biomedicines gut microbiome traumatic brain injury mendelian randomization inflammatory factor immune cell mapped genes |
| title | The Causal Relationship Between Gut Microbiomes, Inflammatory Mediators, and Traumatic Brain Injury in Europeans: Evidence from Genetic Correlation and Functional Mapping Annotation Analyses |
| title_full | The Causal Relationship Between Gut Microbiomes, Inflammatory Mediators, and Traumatic Brain Injury in Europeans: Evidence from Genetic Correlation and Functional Mapping Annotation Analyses |
| title_fullStr | The Causal Relationship Between Gut Microbiomes, Inflammatory Mediators, and Traumatic Brain Injury in Europeans: Evidence from Genetic Correlation and Functional Mapping Annotation Analyses |
| title_full_unstemmed | The Causal Relationship Between Gut Microbiomes, Inflammatory Mediators, and Traumatic Brain Injury in Europeans: Evidence from Genetic Correlation and Functional Mapping Annotation Analyses |
| title_short | The Causal Relationship Between Gut Microbiomes, Inflammatory Mediators, and Traumatic Brain Injury in Europeans: Evidence from Genetic Correlation and Functional Mapping Annotation Analyses |
| title_sort | causal relationship between gut microbiomes inflammatory mediators and traumatic brain injury in europeans evidence from genetic correlation and functional mapping annotation analyses |
| topic | gut microbiome traumatic brain injury mendelian randomization inflammatory factor immune cell mapped genes |
| url | https://www.mdpi.com/2227-9059/13/3/753 |
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