Depression in Parkinson’s Disease: A Trajectory Linking Gut Microbiota and Neuroinflammation

Parkinson’s diseaseParkinson’s disease (PD) is a major neurodegenerative disorder prevalent in old age (above 65 years). It is characterized by motor symptoms such as tremors, rigidity, bradykinesia (slow movement), postural instability and non-motor symptoms like mood disturbances, cognitive impairment, depression, anxietyAnxiety, apathy, and autonomic dysfunction. To date, many therapies have been developed to improve symptoms of PD, but an effective cure for PD remains yet to be discovered. Mounting evidence has suggested an intricate association between PD and depression; however, the key factors leading to depression and associated symptoms in PD remain unknown. Gut microbiota plays a crucial role in the development and progression of PD and depression. Under normal physiological conditions, gut microbiota is essential for improved immunity, metabolism of nutrients, gut barrier integrity and preventionPrevention from pathogenic microbes. However, during gut dysbiosisDysbiosis, the equilibrium is lost, which can disrupt the gut-brain axisGut-brain axis and exacerbate the severity of the PD and depression. The disrupted gut-brain axisGut-brain axis subsequently gives rise to an indispensable phenomenon called neuroinflammationNeuroinflammation. Pro-inflammatory bacteria populations were found in abundance in an unhealthy gut that causes the activation of astrocytes and microgliaMicroglia followed by abrupt release of cytokines in the bloodstream. Breaching the blood–brain barrierBlood-brain barrier, the neuroinflammatory factors damage dopaminergic neurons and serotonergic neurons, leading to PD and depression in the long run. Available therapeutic options for the management of depressive symptoms in PD possess lots of side effects. In recent years, therapeutic strategies for restoring gut microbes, such as probioticsProbiotics, prebioticsPrebiotics and fecal microbiota transplantationFecal microbiota transplantation, have shown promising results against PD and depression. Therefore, understanding the implications of gut-microbiota-associated neuroinflammatory mechanisms in the context of PD and depression becomes essential. This chapter discusses the association between PD and depression and the role of gut microbiota-neuroinflammationNeuroinflammation crosstalk in mediating the disease severity.