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

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.

Clinical predictors of fulminant colitis in patients with clostridium difficile infection

Clostridium difficile infection [CDI] can affect up to 8% of hospitalized patients. Twenty-five percent CDI patients may develop C. difficile associated diarrhea [CDAD] and 1-3% may progress to fulminant C. difficile colitis [FCDC]. Once developed, FCDC has higher rates of complications and mortality. A 10-year retrospective review of FCDC patients who underwent colectomy was performed and compared with randomly selected age- and sex-matched non-fulminant CDAD patients at our institution. FCDC [n=18] and CDAD [m=49] groups were defined clinically, radiologically, and pathologically. Univariate analysis was performed using Chi-square and Student's t test followed by multivariate logistic regression to compute independent predictors. FCDC patients were significantly older [77 +/- 13 years], presented with triad of abdominal pain [89%], diarrhea [72%], and distention [39%]; 28% had prior CDI and had greater hemodynamic instability. In contrast, CDAD patients were comparatively younger [65 +/- 20 years], presented with only 1 or 2 of these 3 symptoms and only 5% had prior CDI. No significant difference was noted between the 2 groups in terms of comorbid conditions, use of antibiotics, or proton pump inhibitor. Leukocytosis was significantly higher in FCDC patients [18.6 +/- 15.8/mm[3]us 10.7 +/- 5.2/mm[3], P=0.04] and further increased until the point of surgery. Use of antiperistaltic medications was higher in FCDC than CDAD group [56% vs 22%; P=0.01]. Our data suggest several clinical and laboratory features in CDI patients, which may be indicative of FCDC. These include old age [>70 years], prior CDI, clinical triad of increasing abdominal pain, distention and diarrhea, profound leukocytosis [>18,000/mm[3]], hemodynamic instability, and use of antiperistaltic medications