Parkinson’s Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation

Abstract

The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson’s disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported in the enteric nervous system, the vagus nerve branches and glial cells. The presence of α-synuclein deposits in the post-mortem brain biopsy in patients with PD has further substantiated the role of inflammation in PD. It has been suggested that the α-synuclein misfolding might begin in the gut and spread “prion like” via the vagus nerve into lower brainstem and ultimately to the midbrain; this is known as the Braak hypothesis. It is noteworthy that the presence of gastrointestinal symptoms (constipation, dysphagia, and hypersalivation), altered gut microbiota and leaky gut have been observed in PD patients several years prior to the clinical onset of the disease. These clinical observations have been supported by in vitro studies in mice as well, demonstrating the role of genetic (α-synuclein overexpression) and environmental (gut dysbiosis) factors in the pathogenesis of PD. The restoration of the gut microbiome in patients with PD may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.

Target Dysbiosis of Gut Microbes as a Future Therapeutic Manipulation in Alzheimer’s Disease

“…In this respect, most clinical and experimental studies have been done in the patients with PD and its animal model. The exciting results with slowing down clinical progress in PD patients were obtained after reconstruction of the gut microbiome by FMT (Dutta et al, 2019 ). A study reported that constipation in a PD patient was clearly relieved after FMT through reconstruction of gut microbiota (Huang et al, 2019 ).…”

Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

“…Previous research has shown that crosstalk between the gut and the brain during PD pathogenesis is mainly influenced by intestinal dysbiosis 21,22,23,24 . This suggests that the gastrointestinal (GI) motility deficits associated with PD, such as constipation, are caused by alterations in the microbial composition of the gut, which disrupt gut homeostasis and increase inflammation and permeability of the gut 25,26,27 . These findings indicate that PD originates in the gut, and that a dysregulated gut microbiome and gut-brain-axis may contribute to PD symptoms.…”

Minireview on the Relations between Gut Microflora and Parkinson’s Disease: Further Biochemical (Oxidative Stress), Inflammatory, and Neurological Particularities

“…The gradual dysfunction of the enteric nervous system (ENS) amplifies the probability of small intestinal bacterial overgrowth (SIBO). There are extensive crosssectional studies which highlight an increased prevalence of SIBO in PD patients compared with the control groups [104]. This is supported by a study in which the authors revealed that SIBO is a condition that could be treated with an appropriate treatment regime, such as rifaximin 200 mg 3 times per day for 1 week, which improves not only gastrointestinal symptoms but also motor fluctuations [105].…”

“…In addition, the clinical features of irritable bowel syndrome (IBS), which include bloating and flatulence, are also common symptoms in PD patients, while constipation or rectal tenesmus does not define the clinical panel of IBS but is however present in patients with PD [104]. However, a recent study revealed an unusual case in which early PD was treated by using antibiotics and colchicine.…”