Vitamin B12 and gut-brain homeostasis in the pathophysiology of ischemic stroke

William Roth, Mansour Mohamadzadeh

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations

Abstract

Stroke is a leading cause of morbidity and mortality worldwide. It inflicts immeasurable suffering on patients and their loved ones and carries an immense social cost. Efforts to mitigate the impact of stroke have focused on identifying therapeutic targets for the prevention and treatment. The gut microbiome represents one such potential target given its multifaceted effects on conditions known to cause and worsen the severity of stroke. Vitamin B12 (VB12) serves as a cofactor for two enzymes, methylmalonyl-CoA synthase and methionine synthase, vital for methionine and nucleotide biosynthesis. VB12 deficiency results in a buildup of metabolic substrates, such as homocysteine, that alter immune homeostasis and contribute to atherosclerotic disorders, including ischemic stroke. In addition to its support of cellular function, VB12 serves as a metabolic cofactor for gut microbes. By shaping microbial communities, VB12 further impacts local and peripheral immunity. Growing evidence suggests that gut dysbiosis-related immune dysfunction induced by VB12 deficiency may potentially contributes to stroke pathogenesis, its severity, and patient outcomes. In this review, we discuss the complex interactions of VB12, gut microbes and the associated metabolites, and immune homeostasis throughout the natural history of ischemic stroke.

Original languageEnglish (US)
Article number103676
JournalEBioMedicine
Volume73
DOIs
StatePublished - Nov 2021

Keywords

  • Atherosclerosis
  • Cerberovascular Disease
  • Cobalamin
  • Homocysteine
  • Inflammation
  • Ischemic stroke
  • Microglia
  • Neuroinflammation
  • Stroke
  • Vitamin B12
  • gut microbiome
  • gut-brain axis
  • innate immunity
  • metabolism
  • metabolites
  • microbiome

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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