Parkinson’s Disease, It Takes Guts: The Correlation between Intestinal Microbiome and Cytokine Network with Neurodegeneration

SIMPLE SUMMARY: Parkinson’s disease is a neurodegenerative disease of the central nervous system, characterized by movement problems and accompanied by behavioral changes such as depression and anxiety. It is a multifactorial condition that is affected by genetic alterations and environmental factors that progressively lead to the death of specialized neurons. This systematic review discusses the attractive hypothesis that gut intestinal dysbiosis is an initial step of a process that leads to Parkinson’s. Gut microbiota alterations and their metabolites can cause intestinal inflammation, but they can also alter gut-brain communication and the brain barrier. This can lead to brain inflammation and the deterioration of brain cells, a process called neurodegeneration. Understanding the role of gut microbiota in the progression of Parkinson’s could be a key element for research toward therapeutic approaches that could delay and even cure the disease. ABSTRACT: Parkinson’s disease is a progressive neurodegenerative disorder with motor, physical and behavioral symptoms that can have a profound impact on the patient’s quality of life. Most cases are idiopathic, and the exact mechanism of the disease’s cause is unknown. The current hypothesis focuses on the gut-brain axis and states that gut microbiota dysbiosis can trigger inflammation and advances the development of Parkinson’s disease. This systematic review presents the current knowledge of gut microbiota analysis and inflammation based on selected studies on Parkinson’s patients and experimental animal models. Changes in gut microbiota correlate with Parkinson’s disease, but only a few studies have considered inflammatory modulators as important triggers of the disease. Nevertheless, it is evident that proinflammatory cytokines and chemokines are induced in the gut, the circulation, and the brain before the development of the disease’s neurological symptoms and exacerbate the disease. Increased levels of tumor necrosis factor, interleukin-1β, interleukin-6, interleukin-17A and interferon-γ can correlate with altered gut microbiota. Instead, treatment of gut dysbiosis is accompanied by reduced levels of inflammatory mediators in specific tissues, such as the colon, brain and serum and/or cerebrospinal fluid. Deciphering the role of the immune responses and the mechanisms of the PD-associated gut microbiota will assist the interpretation of the pathogenesis of Parkinson’s and will elucidate appropriate therapeutic strategies.