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

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

doi:10.3389/fnins.2021.689723

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.

Highlights

Parkinson’s disease (PD) is an incurable disorder affecting more than 6 million people worldwide
We evaluated the serum and fecal levels of calprotectin and zonulin in people with sporadic PD vs. healthy controls
Despite the small sample size, we found that increased serum and fecal calprotectin levels are significantly associated with the risk of PD

Summary

Introduction

Parkinson’s disease (PD) is an incurable disorder affecting more than 6 million people worldwide. Its incidence and prevalence increase with age, culminating in the eighth decade (Collaborators, 2018). Disability is related both to motor (i.e., parkinsonism) and non-motor symptoms (including hyposmia and constipation), slowly progressing over the course of many years (Postuma et al, 2015; Balestrino and Schapira, 2020). The neuropathology of PD is defined by intraneuronal accumulation of alpha-synuclein amyloids, namely Lewy bodies and Lewy neurites, low grade neuroinflammation and selective neuronal dysfunction with subsequent neurodegeneration, involving mainly the aminergic neurocircuits (Braak et al, 2003a; Balestrino and Schapira, 2020). Intestinal inflammation and barrier dysfunction, as well as products of the gut microbiota (that may cause “leaky gut” and/or local inflammation and may trigger or enhance amyloidogenesis), are considered potential key players in the etiopathogenesis of PD (Devos et al, 2013; Houser et al, 2018; Schwiertz et al, 2018; Becker et al, 2019; Mulak et al, 2019; Rolli-Derkinderen et al, 2020; Romano et al, 2021)

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