BACKGROUND Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia,including Alzheimer's dementia,vascular dementia,and dementia in other dise...BACKGROUND Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia,including Alzheimer's dementia,vascular dementia,and dementia in other diseases classified elsewhere.However,the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain unclear.AIM To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization(MR)analysis.METHODS A bidirectional,two-sample,MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study(GWAS)summary data from the MiBioGen consortium alongside GWAS summary statistics for dementia and its subtypes from the FinnGen consortium.Instrumental variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the F-statistic.Five MR methods were employed,and the robustness of our findings was validated.To account for multiple comparisons,we applied the Bonferroni method for P-value adjustment.RESULTS We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes,potentially serving as risk or protective factors for the disease.In addition,reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its subtypes.An exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy.After applying correction for multiple testing,we observed that the order Bacillales(odds ratio:0.830,95%confidence interval:0.740-0.932,P=0.00155,Padjust=0.0311)exhibited a strong association with Alzheimer’s disease-related dementia.CONCLUSION The results suggest that gut microbiota is causally associated with dementia.Our findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention.展开更多
Background:Observational studies have indicated an association between the gut microbiota and the occurrence and progression of aortic aneurysm(AA).However,the causal relationship between the gut microbiota and AA and...Background:Observational studies have indicated an association between the gut microbiota and the occurrence and progression of aortic aneurysm(AA).However,the causal relationship between the gut microbiota and AA and its subtypes remains unclear.This study used Mendelian randomization(MR)to gain new insights into the relationship between the gut microbiota and AA,including AA subtypes.Methods:We used summary data from a genome-wide association study of gut microbiota to determine genetically predicted microbial taxa.Additionally,we predicted causal relationships between the gut microbiota and AA,including AA subtypes.MR was conducted with two-sample MR with the inverse variance weighting,MR-Egger,weighted median,and weighted mode methods to assess the causal relationships.Heterogeneity and pleiotropy were evaluated with the MR-Egger method,Cochran’s Q test,and the MR-PRESSO Global test.The strength of the causal relationships between exposures and outcomes was assessed with Bonferroni correction.The stability of the MR results was evaluated with leave-one-out analyses.Reverse MR analysis was also performed to examine reverse causality.Results:Through MR analysis,after Bonferroni correction,specific microbial taxa were found to have a causal relationship in AA and its subtypes.Specifically,the phylum Lentisphaerae(OR=0.82,P=0.001),class Lentisphaeria(OR=0.81,P=0.0028),and family Bifidobacteriaceae(OR=0.79,P<0.001)were negatively associated with AA risk,whereas the genus Family XIII UCG001(OR=1.33,P<0.001)was positively associated with AA risk.Regarding subtypes,elevated levels of the genus Bilophila(OR=1.36,P<0.001)were closely associated with abdominal aortic aneurysm(AAA)occurrence.Lower levels of the family Bifidobacteriaceae(OR=0.71,P<0.001)and phylum Lentisphaerae(OR=0.81,P=0.0025),and higher levels of the genus Ruminococcaceae UCG014(OR=1.30,P<0.001)exhibited strong causal relationships with thoracic aortic aneurysm(TAA).Conclusion:Our study suggests that specific components of the gut microbiota have causal effects,either beneficial or detrimental,on AA risk,thus providing potentially valuable biomarkers for early diagnosis and potential therapeutic targets.展开更多
Background:Ankle-foot sprains are the most common musculoskeletal injuries,which can impair balance and theoretically increase the risk of falls,but still,there is a lack of evidence supporting the direct association ...Background:Ankle-foot sprains are the most common musculoskeletal injuries,which can impair balance and theoretically increase the risk of falls,but still,there is a lack of evidence supporting the direct association between ankle-foot sprains and the future risk of falls.Methods:UK Biobank cohort was utilized to measure the association between ankle-foot sprains and fall risk with covariates adjusted.Then,the two-sample Mendelian randomization(MR)analysis was applied based on the genetically predicated ankle-foot sprains from FinnGen to validate causal relationship.Finally,genetically predicated cerebellar neuroimaging features were used to explore the mediating role of maladaptive neuroplasticity between ankle-foot sprains and falls by two-step MR analyses.Results:Patients with ankle-foot sprains history exhibited a slightly increased risk of falls than the matched controls before and after adjustment for covariates(odd ratio[OR]ranged from 1.632 to 1.658).Two-sample MR analysis showed that ankle-foot sprains led to a higher risk of falls(OR=1.036)and a lower fractional anisotropy of superior cerebellar peduncle(SCP)(left,β=0.052;right,β=0.053).A trend of mediating effect was observed for the fractional anisotropy of right SCP in the causal effects of ankle-foot sprains on falls(β=0.003).Conclusion:The history of ankle-foot sprains is associated with a slightly increased risk of falls.These findings improve our understanding of the clinical consequences of ankle-foot sprains in terms of fall risk and suggest the importance of adopting more efficient strategies for managing residual functional deficits after the injuries.展开更多
基金Supported by Science and Technology Planning Project of Zhanjiang,No.2021A05071Clinic and Basic Research Project of Guangdong Medical University,No.4SG23284GThe Affiliated Hospital of Guangdong Medical University,No.LCYJ2018A003.
文摘BACKGROUND Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia,including Alzheimer's dementia,vascular dementia,and dementia in other diseases classified elsewhere.However,the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain unclear.AIM To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization(MR)analysis.METHODS A bidirectional,two-sample,MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study(GWAS)summary data from the MiBioGen consortium alongside GWAS summary statistics for dementia and its subtypes from the FinnGen consortium.Instrumental variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the F-statistic.Five MR methods were employed,and the robustness of our findings was validated.To account for multiple comparisons,we applied the Bonferroni method for P-value adjustment.RESULTS We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes,potentially serving as risk or protective factors for the disease.In addition,reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its subtypes.An exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy.After applying correction for multiple testing,we observed that the order Bacillales(odds ratio:0.830,95%confidence interval:0.740-0.932,P=0.00155,Padjust=0.0311)exhibited a strong association with Alzheimer’s disease-related dementia.CONCLUSION The results suggest that gut microbiota is causally associated with dementia.Our findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention.
基金Funding was provided by the National Natural Science Foundation of China(Nos.82222007,82170281,U2004203,and 81800267)Henan Thousand Talents Program(No.ZYQR201912131)+3 种基金Excellent Youth Science Foundation of Henan Province(No.202300410362)Henan Province Medical Science and Technology Key Joint Project(SBGJ202101012)Central Plains Youth Top Talent,Advanced funds(No.2021-CCA-ACCESS-125)Funding for Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University(QNCXTD2023001 and ZYCXTD2023008).
文摘Background:Observational studies have indicated an association between the gut microbiota and the occurrence and progression of aortic aneurysm(AA).However,the causal relationship between the gut microbiota and AA and its subtypes remains unclear.This study used Mendelian randomization(MR)to gain new insights into the relationship between the gut microbiota and AA,including AA subtypes.Methods:We used summary data from a genome-wide association study of gut microbiota to determine genetically predicted microbial taxa.Additionally,we predicted causal relationships between the gut microbiota and AA,including AA subtypes.MR was conducted with two-sample MR with the inverse variance weighting,MR-Egger,weighted median,and weighted mode methods to assess the causal relationships.Heterogeneity and pleiotropy were evaluated with the MR-Egger method,Cochran’s Q test,and the MR-PRESSO Global test.The strength of the causal relationships between exposures and outcomes was assessed with Bonferroni correction.The stability of the MR results was evaluated with leave-one-out analyses.Reverse MR analysis was also performed to examine reverse causality.Results:Through MR analysis,after Bonferroni correction,specific microbial taxa were found to have a causal relationship in AA and its subtypes.Specifically,the phylum Lentisphaerae(OR=0.82,P=0.001),class Lentisphaeria(OR=0.81,P=0.0028),and family Bifidobacteriaceae(OR=0.79,P<0.001)were negatively associated with AA risk,whereas the genus Family XIII UCG001(OR=1.33,P<0.001)was positively associated with AA risk.Regarding subtypes,elevated levels of the genus Bilophila(OR=1.36,P<0.001)were closely associated with abdominal aortic aneurysm(AAA)occurrence.Lower levels of the family Bifidobacteriaceae(OR=0.71,P<0.001)and phylum Lentisphaerae(OR=0.81,P=0.0025),and higher levels of the genus Ruminococcaceae UCG014(OR=1.30,P<0.001)exhibited strong causal relationships with thoracic aortic aneurysm(TAA).Conclusion:Our study suggests that specific components of the gut microbiota have causal effects,either beneficial or detrimental,on AA risk,thus providing potentially valuable biomarkers for early diagnosis and potential therapeutic targets.
基金supported by the National Natural Science Foundation of China[No.81871823,81971583,81671652,8207090113]National Key R&D Program of China[No.2018YFC1312900]+3 种基金Natural Science Foundation of Shanghai[No.20ZR1406400]Science and Technology Commission of Shanghai Municipality[No.18JC1410403]Shanghai Municipal Science and Technology Major Project[No.2017SHZDZX01,2018SHZDZX01]Shanghai Science and Technology Committee[No.22dz1204700].
文摘Background:Ankle-foot sprains are the most common musculoskeletal injuries,which can impair balance and theoretically increase the risk of falls,but still,there is a lack of evidence supporting the direct association between ankle-foot sprains and the future risk of falls.Methods:UK Biobank cohort was utilized to measure the association between ankle-foot sprains and fall risk with covariates adjusted.Then,the two-sample Mendelian randomization(MR)analysis was applied based on the genetically predicated ankle-foot sprains from FinnGen to validate causal relationship.Finally,genetically predicated cerebellar neuroimaging features were used to explore the mediating role of maladaptive neuroplasticity between ankle-foot sprains and falls by two-step MR analyses.Results:Patients with ankle-foot sprains history exhibited a slightly increased risk of falls than the matched controls before and after adjustment for covariates(odd ratio[OR]ranged from 1.632 to 1.658).Two-sample MR analysis showed that ankle-foot sprains led to a higher risk of falls(OR=1.036)and a lower fractional anisotropy of superior cerebellar peduncle(SCP)(left,β=0.052;right,β=0.053).A trend of mediating effect was observed for the fractional anisotropy of right SCP in the causal effects of ankle-foot sprains on falls(β=0.003).Conclusion:The history of ankle-foot sprains is associated with a slightly increased risk of falls.These findings improve our understanding of the clinical consequences of ankle-foot sprains in terms of fall risk and suggest the importance of adopting more efficient strategies for managing residual functional deficits after the injuries.
