Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (3): 1211-1221.doi: 10.4103/NRR.NRR-D-24-00702

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The engineered probiotic strain Lactococcus lactis MG1363-pMG36e-GLP-1 regulates microglial polarization and gut dysbiosis in a transgenic mouse model of Parkinson’s disease

Mengyun Yue1, *, #, Tingtao Chen2, *, #, Wenjie Chen2, 3, Jing Wei2 , Bin Liao1 , Jie Zhang1 , Fangjun Li1 , Daojun Hong1 , Xin Fang1, *   

  1. 1 Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China;  2 National Engineering Research Center of Bioengineering Drugs and Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi Province, China;  3 Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
  • Online:2026-03-15 Published:2025-07-05
  • Contact: Xin Fang, MD, fangx2011@163.com; Tingtao Chen, PhD, chentingtao1984@163.com; Mengyun Yue, MS, yuemengyun1996@163.com.
  • Supported by:
    This study was supported by grants from the Jiangxi Provincial Natural Science Foundation, No. 20242BAB26134 (to XF); the National Natural Science Foundation of China, Nos. 82060638 (to TC), 82060222 (to XF), 82460237 (to XF); the Major Disciplines of Academic and Technical Leaders Project of Jiangxi Province, Nos. 20194BCJ22032 (to TC), 20213BCJL22049 (to XF); and Science and Technology Plan of Jiangxi Health Planning Committee, No. 202210390 (to XF).

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Abstract: Parkinson’s disease is characterized by synucleinopathy-associated neurodegeneration. Previous studies have shown that glucagon-like peptide-1 (GLP-1) has beneficial effects in a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. However, the effect of GLP-1 on intrinsic synuclein malfunction remains unclear. In this study, we investigated the effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism in SncaA53T transgenic mice and explored the underlying mechanisms. Our data showed that Lactococcus lactis MG1363-pMG36e-GLP-1 inhibited dopaminergic neuronal death, reduced pathological aggregation of α-synuclein, and decreased movement disorders in SncaA53T transgenic mice. Furthermore, Lactococcus lactis MG1363-pMG36e-GLP-1 downregulated lipopolysaccharide-related inflammation, reduced cerebral activation of microglia and astrocytes, and promoted cell survival via the GLP-1 receptor/PI3K/Akt pathway in the substantia nigra. Additionally, Lactococcus lactis MG1363-pMG36e-GLP-1 decreased serum levels of pro-inflammatory molecules including lipopolysaccharide, lipopolysaccharide binding protein, interleukin-1β, and interleukin-6. Gut histopathology and western blotting further revealed that Lactococcus lactis MG1363-pMG36e-GLP-1 increased the expression of gut integrity–related proteins and reduced lipopolysaccharide-related inflammation by reversing gut dysbiosis in SncaA53T transgenic mice. Our findings showed that the beneficial effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism traits in SncaA53T transgenic mice is mediated by microglial polarization and the reversal of dysbiosis. Collectively, our findings suggest that Lactococcus lactis MG1363-pMG36e-GLP-1 is a promising therapeutic agent for the treatment of Parkinson’s disease.

Key words: A53T transgenic mice, engineered probiotics, glucagon-like peptide-1, gut dysbacteriosis, gut-brain axis, Lactococcus lactis MG1363-pMG36eGLP-1, microglial polarization, neurodegenerative disease, neuroinflammation, Parkinson’s disease