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

Abstract

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.

Gut-brain axis: Mechanisms and potential therapeutic strategies for ischemic stroke through immune functions

“…Under physiological conditions, the intestinal microbiota of healthy adults is in dynamic balance almost all the time, with the most abundant microbiota being anaerobic bacteria and Clostridium perfringens (Tan et al, 2021;Chidambaram et al, 2022;Peh et al, 2022). In pathological conditions, however, the composition and diversity of the intestinal microbiota are altered.…”

“…Patients with IS often experience complications such as gastrointestinal bleeding, microbiota imbalance, and constipation, which accelerates disease progression and worsens prognosis (Benakis et al, 2016;Kapil et al, 2017;Chen et al, 2019c;Li et al, 2019;Fralick et al, 2020;Pluta et al, 2021). In recent years, researchers have amassed findings that strongly suggest a dynamic association between the gut-brain axis and IS; this topic may become a new research hotspot, which could expedite identification of potential therapeutic targets and eventually result in an intervention that could improve the prognosis of IS (Battaglini et al, 2020;Sinagra et al, 2021;Fang et al, 2022;Peh et al, 2022). 10.3389/fnins.2023.1081347 The gut possesses both digestive and immunomodulatory functions while also hosting a microbial ecosystem.…”

A Review on Polyphenols in Salicornia ramosissima with Special Emphasis on Their Beneficial Effects on Brain Ischemia

“…Accordingly, it was recently reported that polyphenol enriched oat extracts increased the proliferation of beneficial gut microbiota, showing a positive correlation between antioxidant activity and prebiotic effect, which suggest that these polyphenols could be used to regulate the gut microbiota composition [ 131 ]. In this sense, certain changes in gut microbiota have been described to increase the risk of a cerebrovascular event, and, inversely, stroke can induce dysbiosis [ 133 ]. Therefore, a therapeutic effect of phenolic acids and flavonoids by the modulation of gut microbiota in experimental models is plausible and future studies targeting polyphenols–gut interplay are warranted.…”

Systemic immune responses after ischemic stroke: From the center to the periphery

“…Although Treg cells are closely related to neuroprotective function by inhibiting pathogenic T cells, some cytokines produced and secreted by they may associated with neurotoxicity ( 206 , 207 ). In addition, species diversity of intestinal microecology decreases after stroke ( 208 ). Specifically, alterations are observed within the highly abundant phyla Firmicutes, Bacteroidetes and Actinobacteria ( 209 ).…”