Neuroprotective effects of an engineered <i>Escherichia coli</i> Nissle 1917 on Parkinson's disease in mice by delivering <scp>GLP</scp> ‐1 and modulating gut microbiota

Considerable evidence suggests that insulin resistance is closely linked to Parkinson's disease (PD), leading agents aiming at treating diabetes can be regarded as new neuroprotective strategies in PD, notably glucagon-like peptide-1 (GLP-1). However, the extremely short half-life of GLP-1 due degradation by ubiquitous proteolytic enzyme limits its clinical application. In this study, we engineered recombinant integrant probiotic strain Escherichia coli Nissle 1917 (EcN) create a EcN-GLP-1 effectively delivers heterologous molecule. Subsequently, assessed effects on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. We demonstrated treatment could improve motor deficits, increase tyrosine hydroxylase-positive neurons, suppress microglia and astrocyte activation, reduce brain colon inflammation, ameliorate colonic barrier function damaged MPTP induction. Meanwhile, confirmed oral administration restore disturbance gut microbiota MPTP-induced mice, reducing relative abundances Akkermansia Oscillospira, increasing level Prevotella gut. These results support further development an platform which production for gut-brain disorders, such PD.