Disease mechanisms as subtypes: Microbiome

Abnormalities in gut microbiota have been suggested to be involved in the pathophysiology and progression of Parkinson's disease (PD). Gastrointestinal nonmotor symptoms often precede the onset of motor features in PD, suggesting a role for gut dysbiosis in neuroinflammation and α-synuclein (α-syn) aggregation. In the first part of this chapter, we analyze critical features of healthy gut microbiota and factors (environmental and genetic) that modify its composition. In the second part, we focus on the mechanisms underlying the gut dysbiosis and how it alters anatomically and functionally the mucosal barrier, triggering neuroinflammation and subsequently α-syn aggregation. In the third part, we describe the most common alterations in the gut microbiota of PD patients, dividing the gastrointestinal system in higher and lower tract to examine the association between microbiota abnormalities and clinical features. In the final section, we report on current and future therapeutic approaches to gut dysbiosis aiming to either reduce the risk for PD, modify the disease course, or improve the pharmacokinetic profile of dopaminergic therapies. We also suggest that further studies will be needed to clarify the role of the microbiome in PD subtyping and of pharmacological and nonpharmacological interventions in modifying specific microbiota profiles in individualizing disease-modifying treatments in PD.