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 Although studies in recent years have explored the impact of gut microbiota on various sleep characteristics,the interaction between gut microbiota and insomnia remains unclear.Aims We aimed to evaluate the...Background Although studies in recent years have explored the impact of gut microbiota on various sleep characteristics,the interaction between gut microbiota and insomnia remains unclear.Aims We aimed to evaluate the mutual influences between gut microbiota and insomnia.Methods We conducted Mendelian randomisation(MR)analysis using genome-wide association studies datasets on insomnia(N=386533),gut microbiota data from the MiBioGen alliance(N=18340)and the Dutch Microbiome Project(N=8208).The inverse variance weighted(IVW)technique was selected as the primary approach.Then,Cochrane’s Q,Mendelian randomization-Egger(MR-Egger)and MR Pleiotropy RESidual Sum and Outlier test(MRPRESSO)tests were used to detect heterogeneity and pleiotropy.The leave-one-out method was used to test the stability of the MR results.In addition,we performed the Steiger test to thoroughly verify the causation.Results According to IVW,our results showed that 14 gut bacterial taxa may contribute to the risks of insomnia(odds ratio(OR):1.01 to 1.04),while 8 gut bacterial taxa displayed a protective effect on this condition(OR:0.97 to 0.99).Conversely,reverse MR analysis showed that insomnia may causally decrease the abundance of 7 taxa(OR:0.21 to 0.57)and increase the abundance of 12 taxa(OR:1.65 to 4.43).Notably,the genus Odoribacter showed a significant positive causal relationship after conducting the Steiger test.Cochrane’s Q test indicated no significant heterogeneity between most singlenucleotide polymorphisms.In addition,no significant level of pleiotropy was found according to MR-Egger and MRPRESSO.Conclusions Our study highlighted the reciprocal relationships between gut microbiota and insomnia,which may provide new insights into the treatment and prevention of insomnia.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.
文摘Background Although studies in recent years have explored the impact of gut microbiota on various sleep characteristics,the interaction between gut microbiota and insomnia remains unclear.Aims We aimed to evaluate the mutual influences between gut microbiota and insomnia.Methods We conducted Mendelian randomisation(MR)analysis using genome-wide association studies datasets on insomnia(N=386533),gut microbiota data from the MiBioGen alliance(N=18340)and the Dutch Microbiome Project(N=8208).The inverse variance weighted(IVW)technique was selected as the primary approach.Then,Cochrane’s Q,Mendelian randomization-Egger(MR-Egger)and MR Pleiotropy RESidual Sum and Outlier test(MRPRESSO)tests were used to detect heterogeneity and pleiotropy.The leave-one-out method was used to test the stability of the MR results.In addition,we performed the Steiger test to thoroughly verify the causation.Results According to IVW,our results showed that 14 gut bacterial taxa may contribute to the risks of insomnia(odds ratio(OR):1.01 to 1.04),while 8 gut bacterial taxa displayed a protective effect on this condition(OR:0.97 to 0.99).Conversely,reverse MR analysis showed that insomnia may causally decrease the abundance of 7 taxa(OR:0.21 to 0.57)and increase the abundance of 12 taxa(OR:1.65 to 4.43).Notably,the genus Odoribacter showed a significant positive causal relationship after conducting the Steiger test.Cochrane’s Q test indicated no significant heterogeneity between most singlenucleotide polymorphisms.In addition,no significant level of pleiotropy was found according to MR-Egger and MRPRESSO.Conclusions Our study highlighted the reciprocal relationships between gut microbiota and insomnia,which may provide new insights into the treatment and prevention of insomnia.
