The causal relationship of cigarette smoking to metabolic disease risk and the possible mediating role of gut microbiota
Background: Cigarette smoking is a leading cause of preventable death worldwide, with its associated diseases and conditions. Emerging evidence suggests that cigarette smoking contributes to a range of pathological metabolic injuries, including diabetes and nonalcoholic fatty liver disease (NAFLD)....
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324015987 |
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| author | Jingda Zhang Lin Hou Shanxiang Lei Yan Li Guogang Xu |
| author_facet | Jingda Zhang Lin Hou Shanxiang Lei Yan Li Guogang Xu |
| author_sort | Jingda Zhang |
| collection | DOAJ |
| description | Background: Cigarette smoking is a leading cause of preventable death worldwide, with its associated diseases and conditions. Emerging evidence suggests that cigarette smoking contributes to a range of pathological metabolic injuries, including diabetes and nonalcoholic fatty liver disease (NAFLD). The impact of gut microbiota on metabolic health and diseases has been observed, but the causality remains uncertain. Objective: To confirm the causal relationship between cigarette smoking and metabolic diseases, and to investigate the possible mediating effect of gut microbiota on these connections. Methods: The relationships among cigarette smoking, metabolic diseases, and the gut microbiome were analyzed by Univariate Mendelian randomization (UVMR). Furthermore, to mitigate the impact of confounding factors, adjusted models were conducted via the multivariate Mendelian randomization (MVMR) method, aiming to improve the accuracy of prediction. Ultimately, the study evaluated the effect of the intermediary factor, gut microbiome, on the relationship between cigarette smoke and metabolic diseases. Results: The phenomenon that a causal relationship between cigarette smoke (249752 individuals) and gut microbiota (7738 individuals), diabetes (406831 individuals), NAFLD (377998 individuals), hypercholesterolaemia (463010 individuals), and obesity (463010 individuals) was observed using UVMR. In the MVMR model, the genetic connection between cigarette smoking, gut microbiota, and type 2 diabetes remained significant. Of note, paraprevotella_clara served an important mediating role in the type 2 diabetes associated with cigarette smoke. Conclusion: This work offered genetic evidence linking cigarette smoke to metabolic diseases, suggesting that the gut microbiota, particularly paraprevotella_clara, might be a crucial mediator in the development of type 2 diabetes caused by cigarette smoke. Our future studies should consider conducting other ethnic groups MR analyses, particularly with larger sample sizes. Still, more in vivo and in vitro work should be carried out to validate the precise effect and molecular mechanisms of the gut microbiome. |
| format | Article |
| id | doaj-art-8abe4c7f5e8b45aa9c1fc2f876625d2f |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-8abe4c7f5e8b45aa9c1fc2f876625d2f2025-02-12T05:29:27ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117522The causal relationship of cigarette smoking to metabolic disease risk and the possible mediating role of gut microbiotaJingda Zhang0Lin Hou1Shanxiang Lei2Yan Li3Guogang Xu4The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Physiology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100730, ChinaThe Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, ChinaThe Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China; State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China; Corresponding author at: The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China.Background: Cigarette smoking is a leading cause of preventable death worldwide, with its associated diseases and conditions. Emerging evidence suggests that cigarette smoking contributes to a range of pathological metabolic injuries, including diabetes and nonalcoholic fatty liver disease (NAFLD). The impact of gut microbiota on metabolic health and diseases has been observed, but the causality remains uncertain. Objective: To confirm the causal relationship between cigarette smoking and metabolic diseases, and to investigate the possible mediating effect of gut microbiota on these connections. Methods: The relationships among cigarette smoking, metabolic diseases, and the gut microbiome were analyzed by Univariate Mendelian randomization (UVMR). Furthermore, to mitigate the impact of confounding factors, adjusted models were conducted via the multivariate Mendelian randomization (MVMR) method, aiming to improve the accuracy of prediction. Ultimately, the study evaluated the effect of the intermediary factor, gut microbiome, on the relationship between cigarette smoke and metabolic diseases. Results: The phenomenon that a causal relationship between cigarette smoke (249752 individuals) and gut microbiota (7738 individuals), diabetes (406831 individuals), NAFLD (377998 individuals), hypercholesterolaemia (463010 individuals), and obesity (463010 individuals) was observed using UVMR. In the MVMR model, the genetic connection between cigarette smoking, gut microbiota, and type 2 diabetes remained significant. Of note, paraprevotella_clara served an important mediating role in the type 2 diabetes associated with cigarette smoke. Conclusion: This work offered genetic evidence linking cigarette smoke to metabolic diseases, suggesting that the gut microbiota, particularly paraprevotella_clara, might be a crucial mediator in the development of type 2 diabetes caused by cigarette smoke. Our future studies should consider conducting other ethnic groups MR analyses, particularly with larger sample sizes. Still, more in vivo and in vitro work should be carried out to validate the precise effect and molecular mechanisms of the gut microbiome.http://www.sciencedirect.com/science/article/pii/S0147651324015987Tobacco smokingMetabolic diseasesDiabetes mellitus, Type 2MicrobiotaMendelian randomization analysis |
| spellingShingle | Jingda Zhang Lin Hou Shanxiang Lei Yan Li Guogang Xu The causal relationship of cigarette smoking to metabolic disease risk and the possible mediating role of gut microbiota Ecotoxicology and Environmental Safety Tobacco smoking Metabolic diseases Diabetes mellitus, Type 2 Microbiota Mendelian randomization analysis |
| title | The causal relationship of cigarette smoking to metabolic disease risk and the possible mediating role of gut microbiota |
| title_full | The causal relationship of cigarette smoking to metabolic disease risk and the possible mediating role of gut microbiota |
| title_fullStr | The causal relationship of cigarette smoking to metabolic disease risk and the possible mediating role of gut microbiota |
| title_full_unstemmed | The causal relationship of cigarette smoking to metabolic disease risk and the possible mediating role of gut microbiota |
| title_short | The causal relationship of cigarette smoking to metabolic disease risk and the possible mediating role of gut microbiota |
| title_sort | causal relationship of cigarette smoking to metabolic disease risk and the possible mediating role of gut microbiota |
| topic | Tobacco smoking Metabolic diseases Diabetes mellitus, Type 2 Microbiota Mendelian randomization analysis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324015987 |
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