TY - JOUR
T1 - At the Intersection of Gut Microbiome and Stroke
T2 - A Systematic Review of the Literature
AU - Sharma, Vishakha
AU - Sharma, Vaibhav
AU - Shahjouei, Shima
AU - Li, Jiang
AU - Chaudhary, Durgesh
AU - Khan, Ayesha
AU - Wolk, Donna M.
AU - Zand, Ramin
AU - Abedi, Vida
N1 - Funding Information:
The authors would like to extend their appreciation to The Decode Laboratory team members (https://www.thedecodelab.com/ ) for their insightful discussion and support in this project.
Funding Information:
Conflict of Interest: Unrelated to this study, VA had financial research support from the National Institute of Health (NIH) grant No. R56HL116832 sub-awarded to Geisinger during the study period. RZ had financial research support from Bucknell University Initiative Program, Roche—Genentech Biotechnology Company, the Geisinger Health Plan Quality fund, and receives institutional support from Geisinger Health System during the study period.
Publisher Copyright:
© Copyright © 2021 Sharma, Sharma, Shahjouei, Li, Chaudhary, Khan, Wolk, Zand and Abedi.
PY - 2021/9/24
Y1 - 2021/9/24
N2 - Background: Ischemic and hemorrhagic stroke are associated with a high rate of long-term disability and death. Recent investigations focus efforts to better understand how alterations in gut microbiota composition influence clinical outcomes. A key metabolite, trimethylamine N-oxide (TMAO), is linked to multiple inflammatory, vascular, and oxidative pathways. The current biochemical underpinnings of microbial effects on stroke remain largely understudied. The goal of our study is to explore the current literature to explain the interactions between the human gut microbiome and stroke progression, recovery, and outcome. We also provide a descriptive review of TMAO. Methods: A systematic literature search of published articles between January 1, 1990, and March 22, 2020, was performed on the PubMed database to identify studies addressing the role of the microbiome and TMAO in the pathogenesis and recovery of acute stroke. Our initial investigation focused on human subject studies and was further expanded to include animal studies. Relevant articles were included, regardless of study design. The analysis included reviewers classifying and presenting selected articles by study design and sample size in a chart format. Results: A total of 222 titles and abstracts were screened. A review of the 68 original human subject articles resulted in the inclusion of 24 studies in this review. To provide further insight into TMAO as a key player, an additional 40 articles were also reviewed and included. Our findings highlighted that alterations in richness and abundance of gut microbes and increased plasma TMAO play an important role in vascular events and outcomes. Our analysis revealed that restoration of a healthy gut, through targeted TMAO-reducing therapies, could provide alternative secondary prevention for at-risk patients. Discussion: Biochemical interactions between the gut microbiome and inflammation, resulting in metabolic derangements, can affect stroke progression and outcomes. Clinical evidence supports the importance of TMAO in modulating underlying stroke risk factors. Lack of standardization and distinct differences in sample sizes among studies are major limitations.
AB - Background: Ischemic and hemorrhagic stroke are associated with a high rate of long-term disability and death. Recent investigations focus efforts to better understand how alterations in gut microbiota composition influence clinical outcomes. A key metabolite, trimethylamine N-oxide (TMAO), is linked to multiple inflammatory, vascular, and oxidative pathways. The current biochemical underpinnings of microbial effects on stroke remain largely understudied. The goal of our study is to explore the current literature to explain the interactions between the human gut microbiome and stroke progression, recovery, and outcome. We also provide a descriptive review of TMAO. Methods: A systematic literature search of published articles between January 1, 1990, and March 22, 2020, was performed on the PubMed database to identify studies addressing the role of the microbiome and TMAO in the pathogenesis and recovery of acute stroke. Our initial investigation focused on human subject studies and was further expanded to include animal studies. Relevant articles were included, regardless of study design. The analysis included reviewers classifying and presenting selected articles by study design and sample size in a chart format. Results: A total of 222 titles and abstracts were screened. A review of the 68 original human subject articles resulted in the inclusion of 24 studies in this review. To provide further insight into TMAO as a key player, an additional 40 articles were also reviewed and included. Our findings highlighted that alterations in richness and abundance of gut microbes and increased plasma TMAO play an important role in vascular events and outcomes. Our analysis revealed that restoration of a healthy gut, through targeted TMAO-reducing therapies, could provide alternative secondary prevention for at-risk patients. Discussion: Biochemical interactions between the gut microbiome and inflammation, resulting in metabolic derangements, can affect stroke progression and outcomes. Clinical evidence supports the importance of TMAO in modulating underlying stroke risk factors. Lack of standardization and distinct differences in sample sizes among studies are major limitations.
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U2 - 10.3389/fneur.2021.729399
DO - 10.3389/fneur.2021.729399
M3 - Review article
C2 - 34630304
AN - SCOPUS:85117042064
SN - 1664-2295
VL - 12
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 729399
ER -