The Impact of Dysbiosis in Oropharyngeal and Gut Microbiota on Systemic Inflammatory Response and Short-term Prognosis in Acute Ischemic Stroke with Preceding Infection

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2024 Sep 6

PMID 39238889

Authors

Qiuxing He

Guoshun Li

Jiasheng Zhao

Huishan Zhu

Huanhao Mo

Zhanshi Xiong

Zhan Zhao

Jingyi Chen

Weimin Ning

Affiliations

Soon will be listed here.

Abstract

Background: Stroke is a devastating disease and ranks as the second leading cause of death and disability globally. Several studies have shown that preceding infection (PI) of upper respiratory tract are strongly associated with acute ischemic stroke (AIS). However, the clinical implications and underlying pathological mechanisms remain unclear.

Methods: In this study, 16S rRNA gene sequencing was employed to compare the structural characteristics of oropharyngeal and gut microbiota in AIS patients with or without PI and normal controls (NCs; 30 cases each), and systemic inflammatory markers were detected to explore the relationship between upper respiratory tract infections (URTIs) and subsequent stroke severity and functional outcome and the potential mechanism.

Results: We found that patients with AIS-PI exhibited elevated serum WBC, NE, CRP, and Hcy levels, as well as a higher 90-day mRS score. Oropharyngeal and gut microbiota analysis showed that AIS and AIS-PI patients exhibited increased microbial richness in sequence. Principal coordinate analysis of the microbiota demonstrated significant differences in microbiota composition among the three groups. In AIS-PI patients, , , , , and were significantly enriched in the gut. Opportunistic pathogens, including , sp., and , were found to be significantly enriched in the oropharynx. The dysregulated microbiota were positively correlated with systemic inflammatory markers, stroke severity, and poor prognosis. In contrast, short-chain fatty acid-producing bacteria , , , , and were enriched in NCs. Their abundances were negatively correlated with systemic inflammatory markers, stroke severity and poor prognosis.

Conclusion: Our findings suggest that PIs of the upper respiratory tract may contribute to poor short-term functional outcome in AIS patients by causing disturbance of the oropharyngeal and gut microbiota and promoting elevated systemic inflammation levels.

Citing Articles

Gut metagenomic features of frailty.

Jarmukhanov Z, Mukhanbetzhanov N, Vinogradova E, Kozhakhmetov S, Kushugulova A Front Cell Infect Microbiol. 2024; 14:1486579.

PMID: 39654975 PMC: 11625779. DOI: 10.3389/fcimb.2024.1486579.

References

Gao L, Xu T, Huang G, Jiang S, Gu Y, Chen F . Oral microbiomes: more and more importance in oral cavity and whole body. Protein Cell. 2018; 9(5):488-500. PMC: 5960472. DOI: 10.1007/s13238-018-0548-1. View

Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I . Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015; 7(4):2839-49. PMC: 4425176. DOI: 10.3390/nu7042839. View

Wang L, Li Y, Wang C, Guo W, Liu M . C-reactive Protein, Infection, and Outcome After Acute Ischemic Stroke: A Registry and Systematic Review. Curr Neurovasc Res. 2019; 16(5):405-415. DOI: 10.2174/1567202616666191026122011. View

Fu J, Bonder M, Cenit M, Tigchelaar E, Maatman A, Dekens J . The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids. Circ Res. 2015; 117(9):817-24. PMC: 4596485. DOI: 10.1161/CIRCRESAHA.115.306807. View

Jia W, Jiang Y, Jiang Y, Meng X, Li H, Zhao X . Associations between admission levels of multiple biomarkers and subsequent worse outcomes in acute ischemic stroke patients. J Cereb Blood Flow Metab. 2023; 44(5):742-756. PMC: 11197142. DOI: 10.1177/0271678X231214831. View

Barber P, Zhang J, Demchuk A, Hill M, Buchan A . Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility. Neurology. 2001; 56(8):1015-20. DOI: 10.1212/wnl.56.8.1015. View

Chen L, Xu X, Wu X, Cao H, Li X, Hou Z . A comparison of the composition and functions of the oral and gut microbiotas in Alzheimer's patients. Front Cell Infect Microbiol. 2022; 12:942460. PMC: 9448892. DOI: 10.3389/fcimb.2022.942460. View

Rojas-Tapias D, Brown E, Temple E, Onyekaba M, Mohamed A, Duncan K . Inflammation-associated nitrate facilitates ectopic colonization of oral bacterium Veillonella parvula in the intestine. Nat Microbiol. 2022; 7(10):1673-1685. PMC: 9728153. DOI: 10.1038/s41564-022-01224-7. View

Chen S, Dong Z, Cheng M, Zhao Y, Wang M, Sai N . Homocysteine exaggerates microglia activation and neuroinflammation through microglia localized STAT3 overactivation following ischemic stroke. J Neuroinflammation. 2017; 14(1):187. PMC: 5604224. DOI: 10.1186/s12974-017-0963-x. View

10.

Zheng Q, Chen Y, Zhai Y, Meng L, Liu H, Tian H . Gut Dysbiosis Is Associated With the Severity of Cryptogenic Stroke and Enhanced Systemic Inflammatory Response. Front Immunol. 2022; 13:836820. PMC: 9120915. DOI: 10.3389/fimmu.2022.836820. View

11.

Saini V, Guada L, Yavagal D . Global Epidemiology of Stroke and Access to Acute Ischemic Stroke Interventions. Neurology. 2021; 97(20 Suppl 2):S6-S16. DOI: 10.1212/WNL.0000000000012781. View

12.

Balmant B, Fonseca D, Aguiar Prudencio A, Rocha I, Callado L, Tepedino Martins Alves J . Plasma Zonulin, and Sodium Intake Affect C3 Complement Levels in Inactive Systemic Lupus Erythematosus. Nutrients. 2023; 15(8). PMC: 10144636. DOI: 10.3390/nu15081999. View

13.

Gu M, Chen N, Sun H, Li Z, Chen X, Zhou J . Abundance Associates With Severity, Evolution and Outcome of Acute Ischemic Stroke. Front Cell Infect Microbiol. 2021; 11:669322. PMC: 8562073. DOI: 10.3389/fcimb.2021.669322. View

14.

Lira-Junior R, Bostrom E . Oral-gut connection: one step closer to an integrated view of the gastrointestinal tract?. Mucosal Immunol. 2018; 11(2):316-318. DOI: 10.1038/mi.2017.116. View

15.

Yamashiro K, Tanaka R, Urabe T, Ueno Y, Yamashiro Y, Nomoto K . Correction: Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke. PLoS One. 2017; 12(4):e0176062. PMC: 5391100. DOI: 10.1371/journal.pone.0176062. View

16.

Kumar P . From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease. J Physiol. 2016; 595(2):465-476. PMC: 5233655. DOI: 10.1113/JP272427. View

17.

Sadler R, Cramer J, Heindl S, Kostidis S, Betz D, Zuurbier K . Short-Chain Fatty Acids Improve Poststroke Recovery via Immunological Mechanisms. J Neurosci. 2020; 40(5):1162-1173. PMC: 6989004. DOI: 10.1523/JNEUROSCI.1359-19.2019. View

18.

Heikinheimo T, Broman J, Haapaniemi E, Kaste M, Tatlisumak T, Putaala J . Preceding and poststroke infections in young adults with first-ever ischemic stroke: effect on short-term and long-term outcomes. Stroke. 2013; 44(12):3331-7. DOI: 10.1161/STROKEAHA.113.002108. View

19.

Kitamoto S, Nagao-Kitamoto H, Jiao Y, Gillilland 3rd M, Hayashi A, Imai J . The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis. Cell. 2020; 182(2):447-462.e14. PMC: 7414097. DOI: 10.1016/j.cell.2020.05.048. View

20.

Morris G, Fernandes B, Puri B, Walker A, Carvalho A, Berk M . Leaky brain in neurological and psychiatric disorders: Drivers and consequences. Aust N Z J Psychiatry. 2018; 52(10):924-948. DOI: 10.1177/0004867418796955. View