Development of a synbiotic product to modulate the Parkinson’s disease associated microbiome

Descripción del proyecto

Un tratamiento probiótico para la enfermedad de Parkinson

La enfermedad de Parkinson (EP) es un trastorno neurodegenerativo progresivo que se caracteriza por temblores y alteraciones del movimiento. Muchos años antes de la aparición de estos síntomas neurológicos, muchos enfermos de Parkinson presentan síntomas gastrointestinales e inflamación entérica asociados con cambios en la permeabilidad intestinal y la composición de la microbiota. El equipo del proyecto SyMPaBiome, financiado con fondos europeos, trabaja en el desarrollo de una estrategia profiláctica o moduladora de la EP que se puede poner en práctica desde el principio en enfermos de alto riesgo para prevenir o retrasar la aparición de la EP. La solución propuesta tiene como objetivo contrarrestar el metabolito 2-hidroxipiridona, que es producido por arqueobacterias y que parece tener un efecto citotóxico sobre el sistema nervioso entérico.

Objetivo

SyMPaBiome aims to develop a synbiotic, a mixture of live biotherapeutic bacteria and a prebiotic, to modulate the Parkinson’s disease (PD) microbiome, with the threefold aim to decrease (1) the intestinal (neuro-)inflammation and (2) gut permeability associated with PD, as well as to (3) decrease the production of a recently discovered archaeal metabolite linked to PD development and progression. This synbiotic regimen will be the first mechanism-based synbiotic formulation, underpinned by functional read-outs from a unique gut-on-a-chip host-microbe interface model.
PD is the second most common neurodegenerative disease, and remains incurable. Gastrointestinal symptoms precede the characteristic motor symptoms by years to decades and there is evidence supporting initiation of the disease by enteric inflammation and changes in microbial community composition and function. Enteric inflammation in PD is exacerbated by an increased gut permeability and mucus-foraging bacteria are more abundant in the PD microbiome, while fibre-degrading bacteria are decreased. This offers the opportunity to develop prophylactic or disease-modulating products to address these changes in at-risk individuals or PD patients. Recently, the archaeal metabolite 2-hydroxypyridone (2-HP), a co-factor of the hydrogenase in hydrogenotrophic methanogenic archaea, has been implicated in idiopathic PD aetiology. Here, a preventive or disease modulating strategy is proposed to induce a shift in the microbiome and metabolome of at-risk individuals or PD patients and decrease 2-HP production and its cytotoxic effects on the enteric nervous system. In view of this, we aim to develop a synbiotic product that can restore the metabolic profile and microbial community in PD patients and has a protective effect on the intestinal mucus and epithelium. The outcomes of this project will be a synbiotic formulation, ready for in vivo testing, and a toolbox for mechanism-based development of synbiotic products.