Laxative use confounds entacapone-mediated changes to the gut microbiome in Parkinson’s Disease

Abstract

Parkinson’s Disease (PD) is a progressive neurodegenerative disease characterized by defects in endogenous dopamine synthesis. Symptoms include tremors, rigidity, and difficulty moving alongside non-motor symptoms including cognitive decline, depression, and constipation. While Levodopa (L-dopa) remains the standard, and most effective pharmaceutical intervention for managing PD symptoms, Parkinson's disease-modifying medication (PDMMs) such as entacapone, a catechol-O-methyl-transferase (COMT) inhibitor, are often used in combination with L-dopa to extend its half-life. The present study explores the role of entacapone in combination with laxative use  as a confounder in altering PD patients’ gut microbiome composition. Alpha and beta diversity analysis of the gut microbiome of PD patients taking only L-dopa (PD_L) indicated that variations in L-dopa dosage alone does not produce any significant changes. Conversely, significant alterations in gut microbiome were observed in PD patients taking L-dopa and entacapone (PD_LE), indicating that entacapone induces changes in gut microbiome independently of L-dopa, but only if the patient was also taking laxatives. The microbial populations of PD_LE subjects using laxatives also more heavily favored Bifidobacterium, Pediococcus, Ruminococcus, and Enterococcus. Ultimately, by better characterizing the contributions of PDMMs to gut dysbiosis, more informed clinical decisions regarding therapeutic interventions can be implemented to better manage symptoms of Parkinson’s disease.