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Emerging role of gut microbiota in post-stroke cognitive impairment among T2DM patients

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Created On: 31/10/2026

Post-stroke cognitive impairment, Type 2 diabetes

Post-stroke cognitive impairment (PSCI) is markedly exacerbated in type 2 diabetes mellitus (T2DM) sufferers.

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Key take away

Deep metagenomic and metabolomic analyses reveal a tripartite gut ecosystem dysregulation—marked by depleted neuroprotective metabolites, reduced butyrate-producing bacteria, and altered fungal populations—in patients with T2DM and PSCI.

Background

Post-stroke cognitive impairment (PSCI) is markedly exacerbated in type 2 diabetes mellitus (T2DM) sufferers. Yet, the underlying gut microbial and metabolic mechanisms remain poorly understood. While individual alterations in gut bacteria have been noted in diabetes and stroke separately, the integrated microbial, fungal, and metabolic signature specifically driving diabetic PSCI remains uncharacterized. Therefore, this study sought to characterize gut bacterial, fungal, and metabolic alterations associated with PSCI and T2DM (PSCI-DM) and explore their relationships with cognitive performance.

Method

Baseline fecal samples were collected from 28 PSCI-DM patients and 29 matched non-PSCI, non-diabetic controls. Researchers combined deep metagenomic sequencing with untargeted metabolomics to characterize gut bacterial and fungal composition, microbial functional pathways, and metabolite profiles. Associations among microbial features, metabolites, and cognitive performance were evaluated via Montreal Cognitive Assessment (MoCA) scores.

Result

Microbial composition: Although alpha diversity was preserved between groups, subtle yet meaningful shifts occurred in bacterial and fungal composition. The PSCI-DM group exhibited a substantial depletion of beneficial butyrate-producing taxa, including Lachnospira spp. and Butyribacter intestini, alongside an enrichment of Butyricimonas virosa. Furthermore, five fungal species—including Torulaspora globosa and Pichia kudriavzevii—were reduced.
Metabolomic profiling: Untargeted metabolomics identified 45 differentially abundant metabolites. There were notable decreases in neuroprotective compounds, such as 9-oxononanoic acid, C16-ceramide, and nootkatone, alongside increases in metformin and bile acid derivatives.
Functional pathways and correlations: Microbial functional pathways linked to energy metabolism were elevated, whereas those involved in cofactor and neurotransmitter precursor synthesis were reduced. Coordinated cross-kingdom dysregulation was illustrated via significant correlations between specific microbes and metabolites.
Clinical correlations: Independent links with MoCA scores were noted for a limited subset of features, specifically the metabolites Nb-palmitoyltryptamine and pipecolic acid, and the fungal species Pichia kudriavzevii. Mean MoCA scores were lower in the PSCI-DM group (Table 1).

Conclusion

Cognitive decline in diabetic stroke patients was not merely driven by a broad loss of microbial diversity, but rather by targeted dysregulation across a tripartite gut ecosystem (bacteria, fungi, and bioactive metabolites). The concurrent depletion of neuroprotective butyrate producers, specific fungal species, and essential lipid derivatives highlighted critical pathways within the gut-brain axis. These findings offer a basis for investigating targeted probiotic, synbiotic, and metabolite-based strategies to prevent or alleviate PSCI in T2DM sufferers.