Engineered commensal bacteria prevent systemic inflammation-induced memory impairment and amyloidogenesis via producing GLP-1.

The anti-obesity drug GLP-1 has been proven to have an impact on central nervous system, while its extremely short half-life greatly limited its use. In this study, our group constructed two engineering strains MG1363-pMG36e-GLP-1 and VNP20009-pLIVE-GLP-1 to continuously express GLP-1, and supplementation of these strains, especially MG1363-pMG36e-GLP-1, had significantly restored the spatial learning and memory impairment of mice caused by LPS (p < 0.05), suppressed glia activation and Aβ accumulation, and downregulated inflammatory expressions of COX-2, TLR-4, TNF-a, and IL-1β. In addition, MG1363-pMG36e-GLP-1 had significantly blocked the translocation of NF-κB signal and inhibited the phosphorylation of redox-sensitive cytoplasmic signalings of MAPKs and PI3K/AKT. These data suggest that MG1363-pMG36e-GLP-1 could be used as a safe and effective nonabsorbed oral treatment for neuroinflammation-related diseases such as Alzheimer's disease (AD).