Lactobacillus casei serves as a primary functional strain in fecal microbiota-mediated neuroprotection against cerebral ischemia/reperfusion injury.
- 2026-06
- Pathology, research and practice 282
- Li Niu
- Yumin Tan
- Wenlu Cao
- Ermin Wang
- Feng Qi
- PubMed: 41946028
- DOI: 10.1016/j.prp.2026.156441
Objective
Cerebral ischemia/reperfusion (I/R) injury leads to neurological impairment, neuroinflammation, and neuronal death. Emerging evidence suggests gut microbiota influence neural function. This study explores the function of fecal microbiota transplantation (FMT) in cerebral I/R injury and explores the primary functional microbiota strain.Methods
Mouse models of cerebral I/R injury were generated using middle cerebral artery occlusion and reperfusion. Mice received FMT or L. casei administration, with or without the acetylcholine (ACh) receptor antagonist Benzethonium Chloride (BenC). Neurological function was evaluated using Longa scores, and MWM. Brain injury, neuronal death, and apoptosis were assessed via histological assessments. Neuroinflammation and cholinergic anti-inflammatory pathway (CAIP) activation were examined through ELISA, flow cytometry, immunofluorescence, immunohistochemistry, and western blot analyses. Microbiota composition was determined by 16S rRNA sequencing.Results
FMT substantially enhanced neurological function, reduced infarct size, ameliorated neuronal death, and restricted pro-inflammatory cytokine concentration and microglial activation. Lactobacillus casei (L. casei) was identified as the predominant strain enriched by FMT, positively correlating with ACh and α7nAChR levels. Both FMT and L. casei treatments restored serum ACh levels, upregulated α7nAChR expression, and increased anti-inflammatory immune cell infiltration, indicating CAIP activation. However, these neuroprotective effects were diminished by BenC, confirming dependence on cholinergic signaling.Conclusion
This study suggests that FMT and L. casei attenuates I/R-induced neurological injury by activating the CAIP, suppressing neuroinflammation, and promoting neuronal survival. These findings highlight L. casei as a key microbiota-derived mediator of gut-brain axis-dependent neuroprotection.Research Insights
| Supplement | Health Outcome | Effect Type | Effect Size |
|---|---|---|---|
| Lactobacillus casei | Improved Neurobehavioral Function | Beneficial | Large |
| Lactobacillus casei | Improved Neuronal Survival | Beneficial | Large |
| Lactobacillus casei | Reduced Cerebral Ischemia/Reperfusion Injury | Beneficial | Large |
| Lactobacillus casei | Reduced Neuroinflammation | Beneficial | Large |