2. Academic Validation
  3. Lactobacillus casei serves as a primary functional strain in fecal microbiota-mediated neuroprotection against cerebral ischemia/reperfusion injury

Lactobacillus casei serves as a primary functional strain in fecal microbiota-mediated neuroprotection against cerebral ischemia/reperfusion injury

  • Pathol Res Pract. 2026 Jun:282:156441. doi: 10.1016/j.prp.2026.156441.
Li Niu 1,  Yumin Tan 2,  Wenlu Cao 2,  Ermin Wang 2,  Feng Qi 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Qilu Hospital of Shandong University Dezhou Hospital (Dezhou People's Hospital), Dezhou, Shandong 253000, China; Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong 250000, China.
  • 2 Department of Anesthesiology, Qilu Hospital of Shandong University Dezhou Hospital (Dezhou People's Hospital), Dezhou, Shandong 253000, China.
  • 3 Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong 250000, China. Electronic address: [email protected].
PMID: 41946028 DOI: 10.1016/j.prp.2026.156441
Abstract

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.

Keywords

CAIP; Cerebral I/R injury; FMT; Lactobacillus casei; Neuroinflammation.

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