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

Abstract

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).

Neuroprotective effects of an engineered commensal bacterium in the 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine Parkinson disease mouse model via producing glucagon‐like peptide‐1

“…In Fig. 1(a), 3, 1, 3, 6, and 2 mice died in M, PTL, TL, PTH, and TH groups because of the high toxin of MPTP (Langston et al 1984), as the safety of MG1363-pMG36e-GLP-1 has been proven in our previous studies using an Alzheimer disease model (Chen et al 2018). Consistent with previous research, intraperitoneal MPTP injection significantly impaired locomotor function.…”

“…Inspired by Duan and colleagues, we constructed the MG1363 ‐ pMG36e‐GLP‐1 strain that could continuously express sufficient GLP‐1 to ameliorate spatial learning and memory impairment in a Alzheimer's disease mice (Chen et al . ). In this study, we developed a MPTP‐induced Parkinson disease model and evaluated the treatment effect of MG1363 ‐ pMG36e‐GLP‐1 on these model mice.…”

Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1

“…Furthermore an inflammatory status, as seen in pathologies such as type 2 diabetes, might compromise the gut mucosal permeability, leading to the exposure of intestinal EECs to luminal LPS, and a TLR4-mediated release of GLP-1 ( 229 ). This is consistent with the knowledge that GLP-1, as well as glucagon, has shown to possess powerful anti-inflammatory properties in vivo , an area that hold with vast therapeutical potential ( 136 , 230 ).…”

Genetically Engineered Escherichia coli Nissle 1917 Secreting GLP‐1 Analog Exhibits Potential Antiobesity Effect in High‐Fat Diet‐Induced Obesity Mice

“…The use of engineered bacteria to deliver therapeutic molecules has been reported in various studies . Notably, probiotics, including EcN, bifidobacteria, and lactobacilli, have already been engineered to produce GLP‐1 or GLP‐1 analogs to treat diabetes or inflammation‐induced memory impairment .…”