Dataset Information

Serum and Fecal Markers of Intestinal Inflammation and Intestinal Barrier Permeability Are Elevated in Parkinson's Disease.

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 16 unmatched healthy controls. Mean calprotectin was higher in PD, both in serum (14.26 mcg/ml ± 4.50 vs. 5.94 mcg/ml ± 3.80, p = 0.0125) and stool (164.54 mcg/g ± 54.19 vs. 56.19 mcg/g ± 35.88, p = 0.0048). Mean zonulin was also higher in PD serum (26.69 ng/ml ± 3.55 vs. 19.43 ng/ml ± 2.56, p = 0.0046) and stool (100.19 ng/ml ± 28.25 vs. 37.3 ng/ml ± 13.26, p = 0.0012). Calprotectin was above the upper reference limit in 19 PD serums and 6 controls (OR = 10.56, 95% CI = 2.17-51.42, p = 0.0025) and in 20 PD stool samples and 4 controls (OR = 30, 95% CI = 4.75-189.30, p = 0.000045). Increased zonulin was found only in the stool samples of 8 PD patients. Despite the small sample size, our findings are robust, complementing and supporting other recently published results. The relation between serum and fecal calprotectin and zonulin levels and sporadic PD warrants further investigation in larger cohorts.

SUBMITTER: Dumitrescu L

PROVIDER: S-EPMC8249847 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Serum and Fecal Markers of Intestinal Inflammation and Intestinal Barrier Permeability Are Elevated in Parkinson's Disease.

Dumitrescu Laura L Marta Daciana D Dănău Adela A Lefter Antonia A Tulbă Delia D Cozma Liviu L Manole Emilia E Gherghiceanu Mihaela M Ceafalan Laura Cristina LC Popescu Bogdan Ovidiu BO

Frontiers in neuroscience 20210618

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 ...[more]

PMID: 34220443

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Project description:UnlabelledParkinson's disease (PD) is the second most common neurodegenerative disorder of aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein. The finding of these Lewy bodies in the intestinal enteric nerves led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. One potential mechanism for environmental toxin(s) and proinflammatory luminal products to gain access to mucosal neuronal tissue and promote oxidative stress is compromised intestinal barrier integrity. However, the role of intestinal permeability in PD has never been tested. We hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine. To test our hypothesis we evaluated intestinal permeability in subjects newly diagnosed with PD and compared their values to healthy subjects. In addition, we obtained intestinal biopsies from both groups and used immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative stress), and alpha-synuclein. We also evaluated serum markers of endotoxin exposure including LPS binding protein (LBP). Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness) than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha-synuclein (the hallmark of PD), as well as staining for gram negative bacteria and tissue oxidative stress. Our study may thus shed new light on PD pathogenesis as well as provide a new method for earlier diagnosis of PD and suggests potential therapeutic targets in PD subjects.Trial registrationClinicaltrials.gov NCT01155492.

Project description:BackgroundMetabolic Syndrome (MetS) is a clinical diagnosis where patients exhibit three out of the five risk factors: hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hyperglycemia, elevated blood pressure, or increased abdominal obesity. MetS arises due to dysregulated metabolic pathways that culminate with insulin resistance and put individuals at risk to develop various comorbidities with far-reaching medical consequences such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. As it stands, the exact pathogenesis of MetS as well as the involvement of the gastrointestinal tract in MetS is not fully understood. Our study aimed to evaluate intestinal health in human subjects with MetS.MethodsWe examined MetS risk factors in individuals through body measurements and clinical and biochemical blood analysis. To evaluate intestinal health, gut inflammation was measured by fecal calprotectin, intestinal permeability through the lactulose-mannitol test, and utilized fecal metabolomics to examine alterations in the host-microbiota gut metabolism.ResultsNo signs of intestinal inflammation or increased intestinal permeability were observed in the MetS group compared to our control group. However, we found a significant increase in 417 lipid features of the gut lipidome in our MetS cohort. An identified fecal lipid, diacyl-glycerophosphocholine, showed a strong correlation with several MetS risk factors. Although our MetS cohort showed no signs of intestinal inflammation, they presented with increased levels of serum TNFα that also correlated with increasing triglyceride and fecal diacyl-glycerophosphocholine levels and decreasing HDL cholesterol levels.ConclusionTaken together, our main results show that MetS subjects showed major alterations in fecal lipid profiles suggesting alterations in the intestinal host-microbiota metabolism that may arise before concrete signs of gut inflammation or intestinal permeability become apparent. Lastly, we posit that fecal metabolomics could serve as a non-invasive, accurate screening method for both MetS and NAFLD.

Dataset Information

Serum and Fecal Markers of Intestinal Inflammation and Intestinal Barrier Permeability Are Elevated in Parkinson's Disease.

Publications

Serum and Fecal Markers of Intestinal Inflammation and Intestinal Barrier Permeability Are Elevated in Parkinson's Disease.

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