Causality between inflammatory bowel disease and the cerebral cortex: insights from Mendelian randomization and integrated bioinformatics analysis
BackgroundInflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, progressive, and recurrent intestinal condition that poses a significant global health burden. The high prevalence of neuropsychiatric comorbidities in IBD necessitates the deve...
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| Format: | Article |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1175873/full |
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| author | Shubei He Shubei He Shubei He Shubei He Ying Peng Ying Peng Ying Peng Ying Peng Xiaofang Chen Xiaofang Chen Xiaofang Chen Xiaofang Chen Ying Ou |
| author_facet | Shubei He Shubei He Shubei He Shubei He Ying Peng Ying Peng Ying Peng Ying Peng Xiaofang Chen Xiaofang Chen Xiaofang Chen Xiaofang Chen Ying Ou |
| author_sort | Shubei He |
| collection | DOAJ |
| description | BackgroundInflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, progressive, and recurrent intestinal condition that poses a significant global health burden. The high prevalence of neuropsychiatric comorbidities in IBD necessitates the development of targeted management strategies.MethodsLeveraging genetic data from genome-wide association studies and Immunochip genotype analyses of nearly 150,000 individuals, we conducted a two-sample Mendelian randomization study to elucidate the driving force of IBD, UC, and CD on cortical reshaping. Genetic variants mediating the causality were collected to disclose the biological pathways linking intestinal inflammation to brain dysfunction.ResultsHere, 115, 69, and 98 instrumental variables genetically predicted IBD, UC, and CD. We found that CD significantly decreased the surface area of the temporal pole gyrus (β = −0.946 mm2, P = 0.005, false discovery rate-P = 0.085). Additionally, we identified suggestive variations in cortical surface area and thickness induced by exposure across eight functional gyri. The top 10 variant-matched genes were STAT3, FOS, NFKB1, JAK2, STAT4, TYK2, SMAD3, IL12B, MYC, and CCL2, which are interconnected in the interaction network and play a role in inflammatory and immune processes.ConclusionWe explore the causality between intestinal inflammation and altered cortical morphology. It is likely that neuroinflammation-induced damage, impaired neurological function, and persistent nociceptive input lead to morphological changes in the cerebral cortex, which may trigger neuropsychiatric disorders. |
| first_indexed | 2024-03-12T20:53:52Z |
| format | Article |
| id | doaj.art-69d18a2048144995902215fa1249fdc6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T20:53:52Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-69d18a2048144995902215fa1249fdc62023-07-31T22:14:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.11758731175873Causality between inflammatory bowel disease and the cerebral cortex: insights from Mendelian randomization and integrated bioinformatics analysisShubei He0Shubei He1Shubei He2Shubei He3Ying Peng4Ying Peng5Ying Peng6Ying Peng7Xiaofang Chen8Xiaofang Chen9Xiaofang Chen10Xiaofang Chen11Ying Ou12Department of Gastroenterology, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaInstitute of Digestive Diseases of the People's Liberation Army, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaCholestatic Liver Diseases Center, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaCenter for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Gastroenterology, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaInstitute of Digestive Diseases of the People's Liberation Army, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaCholestatic Liver Diseases Center, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaCenter for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Gastroenterology, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaInstitute of Digestive Diseases of the People's Liberation Army, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaCholestatic Liver Diseases Center, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaCenter for Metabolic Associated Fatty Liver Disease, The First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Psychiatry, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaBackgroundInflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, progressive, and recurrent intestinal condition that poses a significant global health burden. The high prevalence of neuropsychiatric comorbidities in IBD necessitates the development of targeted management strategies.MethodsLeveraging genetic data from genome-wide association studies and Immunochip genotype analyses of nearly 150,000 individuals, we conducted a two-sample Mendelian randomization study to elucidate the driving force of IBD, UC, and CD on cortical reshaping. Genetic variants mediating the causality were collected to disclose the biological pathways linking intestinal inflammation to brain dysfunction.ResultsHere, 115, 69, and 98 instrumental variables genetically predicted IBD, UC, and CD. We found that CD significantly decreased the surface area of the temporal pole gyrus (β = −0.946 mm2, P = 0.005, false discovery rate-P = 0.085). Additionally, we identified suggestive variations in cortical surface area and thickness induced by exposure across eight functional gyri. The top 10 variant-matched genes were STAT3, FOS, NFKB1, JAK2, STAT4, TYK2, SMAD3, IL12B, MYC, and CCL2, which are interconnected in the interaction network and play a role in inflammatory and immune processes.ConclusionWe explore the causality between intestinal inflammation and altered cortical morphology. It is likely that neuroinflammation-induced damage, impaired neurological function, and persistent nociceptive input lead to morphological changes in the cerebral cortex, which may trigger neuropsychiatric disorders.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1175873/fullinflammatory bowel diseasecerebral cortexcausalityMendelian randomizationintegrated bioinformatics |
| spellingShingle | Shubei He Shubei He Shubei He Shubei He Ying Peng Ying Peng Ying Peng Ying Peng Xiaofang Chen Xiaofang Chen Xiaofang Chen Xiaofang Chen Ying Ou Causality between inflammatory bowel disease and the cerebral cortex: insights from Mendelian randomization and integrated bioinformatics analysis Frontiers in Immunology inflammatory bowel disease cerebral cortex causality Mendelian randomization integrated bioinformatics |
| title | Causality between inflammatory bowel disease and the cerebral cortex: insights from Mendelian randomization and integrated bioinformatics analysis |
| title_full | Causality between inflammatory bowel disease and the cerebral cortex: insights from Mendelian randomization and integrated bioinformatics analysis |
| title_fullStr | Causality between inflammatory bowel disease and the cerebral cortex: insights from Mendelian randomization and integrated bioinformatics analysis |
| title_full_unstemmed | Causality between inflammatory bowel disease and the cerebral cortex: insights from Mendelian randomization and integrated bioinformatics analysis |
| title_short | Causality between inflammatory bowel disease and the cerebral cortex: insights from Mendelian randomization and integrated bioinformatics analysis |
| title_sort | causality between inflammatory bowel disease and the cerebral cortex insights from mendelian randomization and integrated bioinformatics analysis |
| topic | inflammatory bowel disease cerebral cortex causality Mendelian randomization integrated bioinformatics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1175873/full |
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