Gut microbiota, circulating cytokines and dementia: a Mendelian randomization study

被引:77
作者
Ji, Dong [1 ]
Chen, Wen-Zhu [1 ]
Zhang, Lei [1 ]
Zhang, Zhi-Hua [2 ]
Chen, Li-Jian [1 ]
机构
[1] Anhui Med Univ, Affiliated Hosp 1, Dept Anesthesiol, 218 Jixi Rd, Hefei, Anhui, Peoples R China
[2] Anhui Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Hefei, Anhui, Peoples R China
关键词
Gut microbiota; Dementia; Cytokines; Mendelian randomization; DISEASE;
D O I
10.1186/s12974-023-02999-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
BackgroundSome studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear.MethodsGut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia.ResultsThere were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors.ConclusionsGut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.
引用
收藏
页数:10
相关论文
共 42 条
[1]   Parkinson disease-associated cognitive impairment [J].
Aarsland, Dag ;
Batzu, Lucia ;
Halliday, Glenda M. ;
Geurtsen, Gert J. ;
Ballard, Clive ;
Chaudhuri, K. Ray ;
Weintraub, Daniel .
NATURE REVIEWS DISEASE PRIMERS, 2021, 7 (01)
[2]   Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors [J].
Ahola-Olli, Ari V. ;
Wurtz, Peter ;
Havulinna, Aki S. ;
Aalto, Kristiina ;
Pitkanen, Niina ;
Lehtimaki, Terho ;
Kahonen, Mika ;
Lyytikainen, Leo-Pekka ;
Raitoharju, Emma ;
Seppala, Ilkka ;
Sarin, Antti-Pekka ;
Ripatti, Samuli ;
Palotie, Aarne ;
Perola, Markus ;
Viikari, Jorma S. ;
Jalkanen, Sirpa ;
Maksimow, Mikael ;
Salomaa, Veikko ;
Salmi, Marko ;
Kettunen, Johannes ;
Raitakari, Olli T. .
AMERICAN JOURNAL OF HUMAN GENETICS, 2017, 100 (01) :40-50
[3]   Human gut microbiota: the links with dementia development [J].
Alkasir, Rashad ;
Li, Jing ;
Li, Xudong ;
Jin, Miao ;
Zhu, Baoli .
PROTEIN & CELL, 2017, 8 (02) :90-102
[4]   A predictive regression model of the obesity-related inflammatory status based on gut microbiota composition [J].
Aranaz, Paula ;
Ramos-Lopez, Omar ;
Cuevas-Sierra, Amanda ;
Martinez, J. Alfredo ;
Milagro, Fermin I. ;
Riezu-Boj, Jose I. .
INTERNATIONAL JOURNAL OF OBESITY, 2021, 45 (10) :2261-2268
[5]   Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naive Parkinson's disease patients [J].
Bedarf, J. R. ;
Hildebrand, F. ;
Coelho, L. P. ;
Sunagawa, S. ;
Bahram, M. ;
Goeser, F. ;
Bork, P. ;
Wuellner, U. .
GENOME MEDICINE, 2017, 9
[6]   Meta-analysis and Mendelian randomization: A review [J].
Bowden, Jack ;
Holmes, Michael, V .
RESEARCH SYNTHESIS METHODS, 2019, 10 (04) :486-496
[7]   A review of instrumental variable estimators for Mendelian randomization [J].
Burgess, Stephen ;
Small, Dylan S. ;
Thompson, Simon G. .
STATISTICAL METHODS IN MEDICAL RESEARCH, 2017, 26 (05) :2333-2355
[8]  
Burgess S, 2017, EUR J EPIDEMIOL, V32, P377, DOI 10.1007/s10654-017-0255-x
[9]   Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data [J].
Burgess, Stephen ;
Butterworth, Adam ;
Thompson, Simon G. .
GENETIC EPIDEMIOLOGY, 2013, 37 (07) :658-665
[10]   Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture [J].
Chia, Ruth ;
Sabir, Marya S. ;
Bandres-Ciga, Sara ;
Saez-Atienzar, Sara ;
Reynolds, Regina H. ;
Gustavsson, Emil ;
Walton, Ronald L. ;
Ahmed, Sarah ;
Viollet, Coralie ;
Ding, Jinhui ;
Makarious, Mary B. ;
Diez-Fairen, Monica ;
Portley, Makayla K. ;
Shah, Zalak ;
Abramzon, Yevgeniya ;
Hernandez, Dena G. ;
Blauwendraat, Cornelis ;
Stone, David J. ;
Eicher, John ;
Parkkinen, Laura ;
Ansorge, Olaf ;
Clark, Lorraine ;
Honig, Lawrence S. ;
Marder, Karen ;
Lemstra, Afina ;
St George-Hyslop, Peter ;
Londos, Elisabet ;
Morgan, Kevin ;
Lashley, Tammaryn ;
Warner, Thomas T. ;
Jaunmuktane, Zane ;
Galasko, Douglas ;
Santana, Isabel ;
Tienari, Pentti J. ;
Myllykangas, Liisa ;
Oinas, Minna ;
Cairns, Nigel J. ;
Morris, John C. ;
Halliday, Glenda M. ;
Van Deerlin, Vivianna M. ;
Trojanowski, John Q. ;
Grassano, Maurizio ;
Calvo, Andrea ;
Mora, Gabriele ;
Canosa, Antonio ;
Floris, Gianluca ;
Bohannan, Ryan C. ;
Brett, Francesca ;
Gan-Or, Ziv ;
Geiger, Joshua T. .
NATURE GENETICS, 2021, 53 (03) :294-+