Education, Science, Technology, Innovation and Life
Open Access
Sign In

Causal Relationship between Gut Microbiota and Brain Microbleeds: A Comprehensive Mendelian Randomization Study

Download as PDF

DOI: 10.23977/medbm.2024.020105 | Downloads: 11 | Views: 368

Author(s)

Tianxiang Gao 1, Hanchen Liu 2, Congyan Wu 2, Xiaoxi Zhang 2, Jianmin Liu 2

Affiliation(s)

1 School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
2 Neurovascular Center, Naval Medical University Changhai Hospital, Shanghai, China

Corresponding Author

Tianxiang Gao

ABSTRACT

The background applied in this paper is that considerable evidence has been reported that alterations in gut microbiota composition could cause cerebrovascular diseases. The microbiota-gut-brain axis also hinted at a possible contribution of the gut microbiota to cerebrovascular diseases. However, the causal association between the gut microbiome and the risk of brain microbleeds (BMB) is unclear. The methods applied in this paper is that we performed two-sample bidirectional Mendelian randomization (MR) utilizing the summary-level data of respective genome-wide association study (GWAS) for 211 gut microbial taxa and two BMB phenotypes to reveal the causal association between gut microbiota and BMB.  The results applied in this paper is that we identified 7 causal relationships between genetic liability in the gut microbiome and any BMB, including those involving the genus Lachnospiraceae. We found 13 associations between genetic liability in the gut microbiome and lobar BMB. Moreover, we found 6 associations between genetic liability in the gut microbiome and deep infratentorial BMB. The bidirectional, heterogeneity, and pleiotropy analyses confirmed the robustness of MR results. The conclusion applied in this paper is that our MR analysis revealed that the gut microbiota was causally associated with BMB and may be helpful in providing new insights for further mechanistic and clinical studies of microbiota-mediated cerebrovascular diseases.

KEYWORDS

Gut microbiota, brain microbleeds, Mendelian randomization, Genetics, SNPs

CITE THIS PAPER

Tianxiang Gao, Hanchen Liu, Congyan Wu, Xiaoxi Zhang, Jianmin Liu, Causal Relationship between Gut Microbiota and Brain Microbleeds: A Comprehensive Mendelian Randomization Study. MEDS Basic Medicine (2024) Vol. 2: 30-38. DOI: http://dx.doi.org/10.23977/medbm.2024.020105.

REFERENCES

[1] Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurology. 2013; 12:822-838
[2] Wilson D, Ambler G, Lee KJ, Lim JS, Shiozawa M, Koga M, et al. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: A pooled analysis of individual patient data from cohort studies. Lancet Neurology. 2019;18:653-665
[3] Debette S, Schilling S, Duperron MG, Larsson SC, Markus HS. Clinical significance of magnetic resonance imaging markers of vascular brain injury a systematic review and meta-analysis. Jama Neurology. 2019;76:81-94
[4] Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474:1823-1836
[5] Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ 2018;361:k2179
[6] Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol. 2021;19:55-71
[7] Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. N Engl J Med. 2016;375:2369-2379
[8] Durgan DJ, Lee J, McCullough LD, Bryan RM. Examining the role of the microbiota-gut-brain axis in stroke. Stroke. 2019;50:2270-2277
[9] Iatcu CO, Steen A, Covasa M. Gut microbiota and complications of type-2 diabetes. Nutrients. 2021;14
[10] Honarpisheh P, Bryan RM, McCullough LD. Aging microbiota-gut-brain axis in stroke risk and outcome. Circ Res. 2022; 130:1112-1144
[11] Xiao L, Zheng H, Li J, Zeng M, He D, Liang J, et al. Targeting nlrp3 inflammasome modulates gut microbiota, attenuates corticospinal tract injury and ameliorates neurobehavioral deficits after intracerebral hemorrhage in mice. Biomedicine & Pharmacotherapy. 2022;149:112797
[12] Yu X, Zhou G, Shao B, Zhou H, Xu C, Yan F, et al. Gut microbiota dysbiosis induced by intracerebral hemorrhage aggravates neuroinflammation in mice. Front Microbiol. 2021;12:647304
[13] Davey Smith G, Hemani G. Mendelian randomization: Genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23:R89-R98
[14] Sekula P, Del Greco M F, Pattaro C, Köttgen A. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016;27:3253-3265
[15] Skrivankova VW, Richmond RC, Woolf BAR, Yarmolinsky J, Davies NM, Swanson SA, et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomization: The strobe-mr statement. Jama-Journal of the American Medical Association. 2021;326:1614-1621
[16] Kurilshikov A, Medina-Gomez C, Bacigalupe R, Radjabzadeh D, Wang J, Demirkan A, et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nature Genetics. 2021; 53:156
[17] Pierce BL, Ahsan H, VanderWeele TJ. Power and instrument strength requirements for mendelian randomization studies using multiple genetic variants. International Journal of Epidemiology. 2011;40:740-752
[18] Knol MJ, Lu DW, Traylor M, Adams HHH, Romero JRJ, Smith AV, et al. Association of common genetic variants with brain microbleeds a genome-wide association study. Neurology. 2020;95:E3331-E3343
[19] Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genetic Epidemiology. 2013;37:658-665
[20] Bowden J, Smith GD, Burgess S. Mendelian randomization with invalid instruments: Effect estimation and bias detection through egger regression. International Journal of Epidemiology. 2015;44:512-525
[21] Bowden J, Smith GD, Haycock PC, Burgess S. Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genetic Epidemiology. 2016;40:304-314
[22] Knol MJ, Lu D, Traylor M, Adams HHH, Romero JRJ, Smith AV, et al. Association of common genetic variants with brain microbleeds: A genome-wide association study. Neurology. 2020;95:e3331-e3343
[23] Zhu S, Jiang Y, Xu K, Cui M, Ye W, Zhao G, et al. The progress of gut microbiome research related to brain disorders. Journal of neuroinflammation. 2020;17:25
[24] Wan S, Dandu C, Han G, Guo Y, Ding Y, Song H, et al. Plasma inflammatory biomarkers in cerebral small vessel disease: A review. CNS neuroscience & therapeutics. 2023;29:498-515
[25] Yan Q, Gu Y, Li X, Yang W, Jia L, Chen C, et al. Alterations of the gut microbiome in hypertension. Frontiers in cellular and infection microbiology. 2017;7:381
[26] Hosoki S, Saito S, Tonomura S, Ishiyama H, Yoshimoto T, Ikeda S, et al. Oral carriage of streptococcus mutans harboring the cnm gene relates to an increased incidence of cerebral microbleeds. Stroke. 2020;51:3632-3639
[27] Li W, Wu LX, Huang BS, Yang LJ, Huang JQ, Li ZS, et al. A pilot study: Gut microbiota, metabolism and inflammation in hypertensive intracerebral haemorrhage. Journal of applied microbiology. 2022;133:972-986
[28] Okada H, Kuhn C, Feillet H, Bach JF. The 'hygiene hypothesis' for autoimmune and allergic diseases: An update. Clinical and experimental immunology. 2010;160:1-9
[29] König J, Wells J, Cani PD, García-Ródenas CL, MacDonald T, Mercenier A, et al. Human intestinal barrier function in health and disease. Clinical and translational gastroenterology. 2016;7:e196
[30] Wells JM, Brummer RJ, Derrien M, MacDonald TT, Troost F, Cani PD, et al. Homeostasis of the gut barrier and potential biomarkers. American journal of physiology. Gastrointestinal and liver physiology. 2017;312:G171-g193
[31] Al Bander Z, Nitert MD, Mousa A, Naderpoor N. The gut microbiota and inflammation: An overview. International journal of environmental research and public health. 2020;17
[32] Roberts AB, Gu X, Buffa JA, Hurd AG, Wang Z, Zhu W, et al. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nature medicine. 2018;24:1407-1417
[33] Lee J, d'Aigle J, Atadja L, Quaicoe V, Honarpisheh P, Ganesh BP, et al. Gut microbiota-derived short-chain fatty acids promote poststroke recovery in aged mice. Circulation research. 2020;127:453-465
[34] Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nature reviews. Gastroenterology & hepatology. 2019;16:461-478
[35] Haak BW, Westendorp WF, van Engelen TSR, Brands X, Brouwer MC, Vermeij JD, et al. Disruptions of anaerobic gut bacteria are associated with stroke and post-stroke infection: A prospective case-control study. Translational stroke research. 2021;12:581-592
[36] Akoudad S, Portegies ML, Koudstaal PJ, Hofman A, van der Lugt A, Ikram MA, et al. Cerebral microbleeds are associated with an increased risk of stroke: The rotterdam study. Circulation. 2015;132:509-516
[37] Wilson D, Ambler G, Lee KJ, Lim JS, Shiozawa M, Koga M, et al. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: A pooled analysis of individual patient data from cohort studies. The Lancet. Neurology. 2019;18:653-665
[38] Whelton PK, Carey RM, Aronow WS, Casey DE, Jr., Collins KJ, Dennison Himmelfarb C, et al. 2017 acc/aha/aapa/abc/acpm/ags/apha/ash/aspc/nma/pcna guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A report of the american college of cardiology/american heart association task force on clinical practice guidelines. Circulation. 2018;138:e484-e594
[39] Gao Y, Li D, Lin J, Thomas AM, Miao J, Chen D, et al. Cerebral small vessel disease: Pathological mechanisms and potential therapeutic targets. Frontiers in aging neuroscience. 2022;14:961661
[40] Tonomura S, Gyanwali B. Cerebral microbleeds in vascular dementia from clinical aspects to host-microbial interaction. Neurochemistry international. 2021;148:105073.

Downloads: 752
Visits: 28341

Sponsors, Associates, and Links


All published work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright © 2016 - 2031 Clausius Scientific Press Inc. All Rights Reserved.