4.7 Review

Gut Microbiota and Their Metabolites in Stroke: A Double-Edged Sword

Journal

STROKE
Volume 53, Issue 5, Pages 1788-1801

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.121.036800

Keywords

dysbiosis; gastrointestinal tract; gut-brain axis; gut microbiome; ischemic stroke; short-chain fatty acid; trimethylamine

Funding

  1. Monash Graduate Scholarship
  2. Monash International Tuition Scholarship
  3. National Heart Foundation Future Leader Fellowships [101185, 105663]
  4. Senior Medical Research Fellowship from the Sylvia and Charles Viertel Foundation
  5. National Health & Medical Research Council
  6. National Heart Foundation
  7. National Health & Medical Research Council Development Grant

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In addition to damaging the brain, stroke also affects the gastrointestinal system. The gut microbiota plays a role in stroke onset, prognosis, and recovery. Clinical studies have found reduced gut microbiome diversity in stroke patients, while experimental studies show that gut microbiome composition affects stroke severity.
Besides damaging the brain, stroke causes systemic changes, including to the gastrointestinal system. A growing body of evidence supports the role of the gut and its microbiota in stroke, stroke prognosis, and recovery. The gut microbiota can increase the risk of a cerebrovascular event, playing a role in the onset of stroke. Conversely, stroke can induce dysbiosis of the gut microbiota and epithelial barrier integrity. This has been proposed as a contributor to systemic infections. In this review, we describe the role of the gut microbiota, microbiome and microbiota-derived metabolites in experimental and clinical stroke, and their potential use as therapeutic targets. Fourteen clinical studies have identified 62 upregulated (eg, Streptococcus, Lactobacillus, Escherichia) and 29 downregulated microbial taxa (eg, Eubacterium, Roseburia) between stroke and healthy participants. The majority found that stroke patients have reduced gut microbiome diversity. However, other nonbacterial microorganisms are yet to be studied. In experimental stroke, severity is dependent on gut microbiome composition, whereas the latter can greatly change with antibiotics, age, and diet. Consumption of foods rich in choline and L-carnitine are positively associated with stroke onset via production of trimethylamine N-oxide in experimental and clinical stroke. Conversely, in mice, consumption of dietary fiber improves stroke outcome, likely via gut microbiota-derived metabolites called short-chain fatty acids, such as acetate, propionate, and butyrate. The majority of the evidence, however, comes from experimental studies. Clinical interventions targeted at gut microbiota-derived metabolites as new therapeutic opportunities for stroke prevention and treatment are warranted.

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