Potential of Prebiotic Butyrogenic Fibers in Parkinson's Disease

Abstract

Parkinson's Disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. Recent evidence supports the involvement of the gastrointestinal tract in PD pathogenesis, including alterations in microbiota and intestinal permeability. Apart from being the preferred energy source for colonic epithelial cells, butyrate is involved in anti-inflammatory, enteroendocrine and epigenetic mechanisms that influence colonic and systemic health, including brain function. A few studies using oral administration of sodium butyrate indicate beneficial effects in PD animal models; however, prebiotic fibers that generate butyrate locally in the gut may be more effective. The design and selection of butyrogenic prebiotic fibers would allow preclinical studies to evaluate how gut-derived butyrate could affect PD pathophysiology. This review describes potential benefits of increasing gut butyrate production in PD through a prebiotic approach. Moreover, physico-chemical features of prebiotic fibers that target butyrogenic colonic bacteria are discussed.

Keywords: Parkinson's disease; butyrate; dietary fiber; gut microbiota; prebiotics.

Figure 1

Dietary fiber approach to increase gut-produced butyrate and pathways that have potential benefits to Parkinson's Disease. Insoluble dietary fibers with specific chemical structures are fermented by butyrate producers in the gut (e.g., Clostridium Cluster XIVa and IV species). The butyrate produced during fermentation supports gut barrier function through the stimulation of mucus production and tight junction assemblies, and minimizing antigen translocation and inflammation. Butyrate also regulates inflammatory pathways through G protein-coupled receptors (GPCR) in enterocytes and through inhibition of histone deacetylase (HDAC) in macrophages. GPCR signaling in enteroendocrine cells (EEC) induce secretion of hormones (e.g., glucagon-like peptide-1 [GLP-1] and peptide YY[PYY]) that act in many organs, including the brain.