Current issue
Archive
Manuscripts accepted
About the Journal
Editorial office
Editorial board
Section Editors
Abstracting and indexing
Subscription
Contact
Ethical standards and procedures
Most read articles
Instructions for authors
Article Processing Charge (APC)
Regulations of paying article processing charge (APC)
PUBLIC HEALTH / CLINICAL RESEARCH
Exploring the mediating role of the plasma lipidome in the pathway from the gut microbiota to dementia: a Mendelian randomization study
1
Department of Neurology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China
2
Department of Military Health Statistics, Naval Medical University, Shanghai, China
These authors had equal contribution to this work
Submission date: 2024-08-15
Final revision date: 2025-01-23
Acceptance date: 2025-02-15
Online publication date: 2025-04-27
Corresponding author
Cheng Wu
Department of Military Health Statistics Naval Medical University 800 Xiangyin Road Yangpu District 200433, Shanghai, China
Department of Military Health Statistics Naval Medical University 800 Xiangyin Road Yangpu District 200433, Shanghai, China
Yongbo Hu
Department of Neurology Shanghai Changhai Hospital Naval Medical University 168 Changhai Road Yangpu District 200433, Shanghai China
Department of Neurology Shanghai Changhai Hospital Naval Medical University 168 Changhai Road Yangpu District 200433, Shanghai China
Xiaoying Bi
Department of Neurology Shanghai Changhai Hospital Naval Medical University 168 Changhai Road Yangpu District 200433, Shanghai China
Department of Neurology Shanghai Changhai Hospital Naval Medical University 168 Changhai Road Yangpu District 200433, Shanghai China
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Previous studies have indicated a potential association between the gut microbiota (GM) and dementia; however, the exact cause-and-effect relationships between GM, various types of dementia, and the potential influence of the plasma lipidome as intermediaries are still unclear.
Material and methods:
We used genome-wide association study (GWAS) data to identify GM taxa, plasma lipid species (lipidome), and five types of dementia: Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), frontotemporal dementia (FTD) and vascular dementia (VD). We used Mendelian randomization (MR) to investigate the possible causal connections among the GM, plasma lipidome, and dementias. The inverse variance weighting (IVW) method served as the primary statistical approach. We investigated the role of plasma lipidome as a potential mediating factor in this relationship.
Results:
A total of 41 positive and 39 negative causal relationships between genetic susceptibility in the GM taxa or bacterial pathways and dementia, as well as 14 negative causal relationships between the plasma lipidome and dementias, were identified. Additionally, only 1 potential mediation pathway was identified as having a significant mediating effect.
Conclusions:
Our results suggest a link between the GM and the plasma lipidome with five distinct types of dementia, indicating that the phosphatidylcholine (O-16:1_18:2) level could play a role in the pathway from the species Bacteroides coprocola to vascular dementia.
Previous studies have indicated a potential association between the gut microbiota (GM) and dementia; however, the exact cause-and-effect relationships between GM, various types of dementia, and the potential influence of the plasma lipidome as intermediaries are still unclear.
Material and methods:
We used genome-wide association study (GWAS) data to identify GM taxa, plasma lipid species (lipidome), and five types of dementia: Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), frontotemporal dementia (FTD) and vascular dementia (VD). We used Mendelian randomization (MR) to investigate the possible causal connections among the GM, plasma lipidome, and dementias. The inverse variance weighting (IVW) method served as the primary statistical approach. We investigated the role of plasma lipidome as a potential mediating factor in this relationship.
Results:
A total of 41 positive and 39 negative causal relationships between genetic susceptibility in the GM taxa or bacterial pathways and dementia, as well as 14 negative causal relationships between the plasma lipidome and dementias, were identified. Additionally, only 1 potential mediation pathway was identified as having a significant mediating effect.
Conclusions:
Our results suggest a link between the GM and the plasma lipidome with five distinct types of dementia, indicating that the phosphatidylcholine (O-16:1_18:2) level could play a role in the pathway from the species Bacteroides coprocola to vascular dementia.
REFERENCES (48)
1.
GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18: 459-80.
2.
GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health 2022; 7: e105-25.
3.
Elahi FM, Miller BL. A clinicopathological approach to the diagnosis of dementia. Nat Rev Neurol 2017; 13: 457-76.
4.
Valletta M, Vetrano DL, Xia X, et al. Multimorbidity patterns and 18-year transitions from normal cognition to dementia and death: a population-based study. J Internal Med 2023; 294: 326-35.
5.
Wimo A, Seeher K, Cataldi R, et al. The worldwide costs of dementia in 2019. Alzheimers Dement 2023; 19: 2865-73.
6.
Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, Soleimanpour S. A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin Microbiol Rev 2022; 35: e0033820.
7.
Fan S, Guo W, Xiao D, et al. Microbiota-gut-brain axis drives overeating disorders. Cell Metabol 2023; 35: 2011-27.
8.
Agirman G, Yu KB, Hsiao EY. Signaling inflammation across the gut-brain axis. Science 2021; 374: 1087-92.
9.
Loh JS, Mak WQ, Tan LKS, et al. Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transd Targeted Ther 2024; 9: 37.
10.
Wang X, Ma H, Li X, et al. Association of cardiovascular health with life expectancy free of cardiovascular disease, diabetes, cancer, and dementia in UK adults. JAMA Inter Med 2023; 183: 340-9.
11.
Ferguson EL, Zimmerman SC, Jiang C, et al. Low- and high-density lipoprotein cholesterol and dementia risk over 17 years of follow-up among members of a large health care plan. Neurology 2023; 101: e2172-84.
12.
Baloni P, Arnold M, Buitrago L, et al. Multi-Omic analyses characterize the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer’s disease. Commun Biol 2022; 5: 1074.
13.
Green RE, Lord J, Scelsi MA, et al.; Insight 46 study team. Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer’s disease. Alzheimer’s Res Ther 2023; 15: 38.
14.
Yoon JH, Seo Y, Jo YS, et al. Brain lipidomics: From functional landscape to clinical significance. Sci Adv 2022; 8: eadc9317.
15.
Luo J, Yang H, Song BL. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol 2020; 21: 225-45.
16.
Chen C, Liao J, Xia Y, et al. Gut microbiota regulate Alzheimer’s disease pathologies and cognitive disorders via PUFA-associated neuroinflammation. Gut 2022; 71: 2233-52.
17.
Tam V, Patel N, Turcotte M, Bossé Y, Paré G, Meyre D. Benefits and limitations of genome-wide association studies. Nat Rev Genet 2019; 20: 467-84.
18.
Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: a review. Research Synthesis Methods 2019; 10: 486-96.
19.
Lopera-Maya EA, Kurilshikov A, van der Graaf A, et al. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project. Nat Genet 2022; 54: 143-51.
20.
Ottensmann L, Tabassum R, Ruotsalainen SE, et al. Genome-wide association analysis of plasma lipidome identifies 495 genetic associations. Nat Commun 2023; 14: 6934.
21.
Chia R, Sabir MS, Bandres-Ciga S, et al. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. Nat Genet 2021; 53: 294-303.
22.
Cohen JF, Chalumeau M, Cohen R, Korevaar DA, Khoshnood B, Bossuyt PM. Cochran’s Q test was useful to assess heterogeneity in likelihood ratios in studies of diagnostic accuracy. J Clin Epidemiol 2015; 68: 299-306.
23.
Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet 2018; 50: 693-8.
24.
Khan R, Di Gesù CM, Lee J, McCullough LD. The contribution of age-related changes in the gut-brain axis to neurological disorders. Gut Microbes 2024; 16: 2302801.
25.
Kim JS, Park H, Lee JH, et al. Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer’s dementia following fecal microbiota transplantation: a preliminary study. Ther Adv Neurol Disord 2024; 17: 17562864231218181.
26.
Li C, Wang N, Zheng G, Yang L. Oral administration of resveratrol-selenium-peptide nanocomposites alleviates Alzheimer’s disease-like pathogenesis by inhibiting A aggregation and regulating gut microbiota. ACS Appl Mater Interfaces 2021; 13: 46406-20.
27.
Sun P, Zhu H, Li X, et al. Comparative metagenomics and metabolomes reveals abnormal metabolism activity is associated with gut microbiota in Alzheimer’s disease mice. Int J Mol Sci 2022; 23: 11560.
28.
Hung CC, Chang CC, Huang CW, Nouchi R, Cheng CH. Gut microbiota in patients with Alzheimer’s disease spectrum: a systematic review and meta-analysis. Aging 2022; 14: 477-96.
29.
Jemimah S, Chabib CMM, Hadjileontiadis L, AlShehhi A. Gut microbiome dysbiosis in Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis. PLoS One 2023; 18: e0285346.
30.
Chiroma SM, Mohd Moklas MA, Mat Taib CN, Baharuldin MTH, Amon Z. d-galactose and aluminium chloride induced rat model with cognitive impairments. Biomed Pharmacother 2018; 103: 1602-8.
31.
Shwe T, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. Role of D-galactose-induced brain aging and its potential used for therapeutic interventions. Exp Gerontol 2018; 101: 13-36.
32.
Tynkkynen J, Chouraki V, van der Lee SJ, et al. Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer’s disease: a prospective study in eight cohorts. Alzheimer’s Dementia 2018; 14: 723-33.
33.
Yang B, Sun T, Chen Y, Xiang H, Xiong J, Bao S. The role of gut microbiota in mice with bile duct ligation-evoked cholestatic liver disease-related cognitive dysfunction. Front Microbiol 2022; 3: 909461.
34.
Krypotou E, Townsend GE, Gao X, et al. Bacteria require phase separation for fitness in the mammalian gut. Science 2023; 379: 1149-56.
35.
Li Y, Chen Y, Fan Y, Chen Y, Chen Y. Dynamic network modeling of gut microbiota during Alzheimer’s disease progression in mice. Gut Microbes 2023; 15: 2172672.
36.
Stopa EG, Tanis KQ, Miller MC, et al. Comparative transcriptomics of choroid plexus in Alzheimer’s disease, frontotemporal dementia and Huntington’s disease: implications for CSF homeostasis. Fluids Barriers CNS 2018; 15: 18.
37.
Klein RD, Shu Q, Cusumano ZT, et al. Structure-function analysis of the curli accessory protein CsgE defines surfaces essential for coordinating amyloid fiber formation. mBio 2018; 9: e01349-18.
38.
Chang CH, Lin CH, Lane HY. d-glutamate and Gut Microbiota in Alzheimer’s Disease. Int J Mol Sci 2020; 21: 2676.
39.
Heravi FS, Naseri K, Hu H. Gut microbiota composition in patients with neurodegenerative disorders (Parkinson’s and Alzheimer’s) and healthy controls: a systematic review. Nutrients 2023; 15: 4365.
40.
Un-Nisa A, Khan A, Zakria M, et al. Updates on the role of probiotics against different health issues: focus on Lactobacillus. Int J Mol Sci 2022; 24: 142.
41.
Bedarf JR, Hildebrand F, Coelho LP, et al. Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson’s disease patients. Genome Med 2017; 9: 39.
42.
Aljumaah MR, Bhatia U, Roach J, Gunstad J, Azcarate Peril MA. The gut microbiome, mild cognitive impairment, and probiotics: a randomized clinical trial in middle-aged and older adults. Clin Nutr 2022; 41: 2565-76.
43.
Du Y, Li X, An Y, Song Y, Lu Y. Association of gut microbiota with sort-chain fatty acids and inflammatory cytokines in diabetic patients with cognitive impairment: a cross-sectional, non-controlled study. Front Nutr 2022; 9: 930626.
44.
Wu PH, Tseng YF, Liu W, et al. Exploring the relationship between gut microbiome composition and blood indole-3-acetic acid in hemodialysis patients. Biomedicines 2024; 12: 148.
45.
Xia Y, Xiao Y, Wang ZH, et al. Bacteroides Fragilis in the gut microbiomes of Alzheimer’s disease activates microglia and triggers pathogenesis in neuronal C/EBP transgenic mice. Nat Commun 2023; 14: 5471.
46.
Zhao Y, Jaber VR, Pogue AI, Sharfman NM, Taylor C, Lukiw WJ. Lipopolysaccharides (LPSs) as potent neurotoxic glycolipids in Alzheimer’s disease (AD). Int J Mol Sci 2022; 23: 12671.
47.
Custodia A, Romaus-Sanjurjo D, Aramburu-Núñez M, et al. Ceramide/sphingosine 1-phosphate axis as a key target for diagnosis and treatment in Alzheimer’s disease and other neurodegenerative diseases. Int J Mol Sci 2022; 23: 8082.
48.
Ylilauri MPT, Voutilainen S, Lönnroos E, et al. Associations of dietary choline intake with risk of incident dementia and with cognitive performance: the Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Clin Nutr 2019; 110: 1416-23.
Share
RELATED ARTICLE
| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
