AUTHOR=Dumitrescu Laura , Marta Daciana , Dănău Adela , Lefter Antonia , Tulbă Delia , Cozma Liviu , Manole Emilia , Gherghiceanu Mihaela , Ceafalan Laura Cristina , Popescu Bogdan Ovidiu 

TITLE=Serum and Fecal Markers of Intestinal Inflammation and Intestinal Barrier Permeability Are Elevated in Parkinson’s Disease

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 15 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.689723

DOI=10.3389/fnins.2021.689723

ISSN=1662-453X

ABSTRACT=Parkinson’s disease (PD) is characterized by alpha-synuclein misfolding with subsequent intraneuronal amyloid formation and accumulation, low grade neuroinflammatory changes, and selective neurodegeneration. Available evidence suggests that the pathology usually begins in the gut and olfactory mucosa, spreading to the brain via the vagus and olfactory nerves, by a prion-like mechanism. A causal relationship has not been established, but gut dysbiosis is prevalent in PD and may lead to intestinal inflammation and barrier dysfunction. Additionally, epidemiological data indicate a link between inflammatory bowel diseases and PD. Calprotectin and zonulin are markers of intestinal inflammation and barrier permeability, respectively. We evaluated their serum and fecal levels in 22 patients with sporadic PD and 8 unmatched healthy controls. Mean calprotectin was higher in PD, both in serum (14.26 mcg/ml ± 4.50 versus 2.14 mcg/ml ± 0.86, p = 0.004) and stool (164.54 mcg/g ± 54.19 versus 33.81 mcg/g ±13.38, p = 0.009). Mean zonulin was also higher in PD serum (p = 0.021) and stool (p = 0.054). Calprotectin was above the upper reference limit in 19 PD serums and 1 control (OR = 44.33, 95% CI = 3.93 – 500.29, p = 0.0004) and in 20 PD stool samples and 1 control (OR = 70, 95% CI = 5.46 – 896.63, p = 0.0001). Increased zonulin was found only in the stool samples of 8 PD patients. Despite methodological limitations, our findings support other recently published results, underlining the importance of further investigating the gastrointestinal tract in PD. The coexistence of an amyloidogenic gut microbiota with intestinal inflammation (leading to local overexpression of alpha-synuclein) and altered intestinal barrier permeability (exposing alpha-synuclein to the amyloidogenic xenobiotics) may play a key role in triggering the initial alpha-synuclein conformational changes in some people with sporadic PD. Disturbances in the microbiota-gut-brain axis may also contribute to neurodegeneration, interfering with neuronal susceptibility to stressors and ultimately with neuronal survival.