Acute stroke is the second leading cause of death and the third leading cause of disability in the world, with ~25 million cases being diagnosed yearly. Stroke causes brain injury, which is worsened by the consequent inflammation. This is further exacerbated by stroke-related changes in the gut and other body systems, like the kidneys and lungs. The gut microbiota plays a vital role in the host’s metabolic activity. Gut dysbiosis appears to worsen the risk for stroke. Conversely, via the gut-brain axis, acute stroke can cause gut dysbiosis. The gut microbiota also affects the prognosis of the stroke by influencing its clinical severity and course.
Earlier studies have suggested that pro-inflammatory bacteria like Prevotella and Enterobacteriaceae may be increased in such patients. These activate inflammatory pathways and ultimately result in higher levels of inflammatory chemicals in the body, such as TNF-α, IL-6, and IL-1β. At the same time, beneficial bacteria like Faecalibacterium prausnitzii and Bifidobacterium, which also counter inflammation, are reduced, causing short-chain fatty acid (SCFA) production to drop. This could inhibit regulatory T cell (Treg) activity, causing Th17 cells to become hyperactive and trigger inflammation. The combined result of these changes is heightened neuroinflammation of the stroke-affected brain.
Additionally, Lactobacillus abundance is reduced, decreasing the neuroprotective inhibitory neurotransmitter γ-aminobutyric acid (GABA) production. Such observations have helped explain the occurrence of post-stroke gut dysbiosis in animal models. Another way to study this is via metabolomics, where the metabolites produced by gut microbes are profiled. Such knowledge could help identify the pathways underlying inflammation and brain injury in acute stroke that are mediated by gut dysbiosis. The gut microbiota produces essential amino acids and many more other metabolites, which include neurotransmitters that affect the gut-brain axis and brain function.
Other molecules (aromatics, short chain fatty acids) cross the intestinal epithelial barrier to enter the bloodstream, allowing them to penetrate the brain and evoke microglial responses. Still, much remains to be known about the gut microbiota and its metabolites in the context of acute stroke. The current study aimed to contribute to this research gap. To enlarge the casistics of the relationsp between stroke and dysbiosis, a team of scientists included 20 healthy people and 20 patients with acute stroke in their new study. Untargeted metabolomics was performed on n=6 per group, selected for reproducibility.
Acute stroke patients had markedly altered gut microbiota regarding community structure and composition. Their community structure was different, with higher phylogenetic diversity but lower evenness, dominated by the phyla Firmicutes, Bacteroidota, and Proteobacteria. Compared with healthy individuals, patients with acute stroke had higher abundances of Faecalibacterium and Agathobacter (with Bacteroides more enriched in healthy controls). Deep shifts in its functional activity accompanied these marked alterations in the gut microbiota composition. Energy-associated and biosynthetic pathways were especially vulnerable to these shifts.
The fecal metabolite pattern also changed dramatically compared with healthy controls. The metabolism of nitrogen, glutathione and phenylalanine was more frequently upregulated in acute stroke patients. While 122 metabolites were raised i, some were significantly lower. Interestingly, SCFA levels were comparable in both groups. Certain genera acted as hubs in the microbial community, and these varied significantly between healthy controls and stroke patients. Increased abundances of Fecalibacterium and Agathobacter were closely associated with upregulated metabolites. In addition, stroke patients had a more discrete or scattered association of metabolites with microbes than healthy individuals.
Specific microbial genera were associated with the top ten differential metabolites in the two cohorts. Notably, the abundance of anti-inflammatory microbiota was increased significantly, accompanied by elevated levels of certain metabolites, such as 6,9,12,15,18,21-tetracosahexaenoic acid and bufadienolide. This suggests that the altered microbiota accounted for the shift in metabolite profile in stroke patients. Conversely, these microbes were negatively correlated with metabolites like urobilin, adrenic acid and 2-hydroxy-6-pentadecylbenzoic acid, that could be inflammatory. Overall, the authors hypothesize a compensatory, potentially anti-inflammatory shift in the acute phase.
They, however, emphasize the need for causal validation and proposed that acute stroke may cause the anti-inflammatory gut microbes to change their production of key metabolites to modulate the inflammatory response. Since conflicting findings have been reported in other studies, these results need to be validated, preferably using serum markers of inflammation and longitudinal follow-up to identify the course of gut microbiota changes after acute stroke. The gut-brain axis may well mediate these shifts. If validated, this may represent potential therapeutic targets for acute stroke management.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Chen J, Wu X et al. Front Microbiol. 2025 Sep; 16:1580231.
Zhang L et al. Front Med (Lausanne). 2025 Jul; 12:1618947.
Obi-Azuike C, Ebiai R et al. Brain Behav. 2023 ì; 13(6):e3037.
Battaglini D, Pimentel CPM et al. Front. Neurol. 2018; 11:598.
