Intestinal inflammation and compromised barrier function in idiopathic parkinsonism: scenario captured by systematic review

Abstract

Aim: To address how common are intestinal inflammation and compromised barrier function in idiopathic parkinsonism (IP), any potential treatment benefits, outcome of not treating, and whether screening is worthwhile. This may provide the missing link between systemic/brain inflammation in IP and implicated gastrointestinal microbiota/specific pathogens. Methods: Search strategy was based on PRISMA guidelines. Fifteen of the 1395 articles (1995-2020) identified met the inclusion criteria. Seven gave results on more than one intestinal modality: inflammation, permeability, integrity, and bacterial translocation. Results: The inter-relationship of IP with intestinal inflammation and bacterial translocation is firmly established, lacking only random sample surveys to meet Level-1 Oxford Centre for Evidence-Based Medicine evidence. Evidence for reduced integrity is limited to 2 small studies of tight-junction proteins in colonic biopsies. No overall conclusion can be drawn from studies of faecal and circulating markers of integrity: evidence based on an assay that recognizes wider zonulin family, not the specific peptide exclusively, was censored. Evidence for increased permeability is Page 2 Umamahesan et al. Neuroimmunol Neuroinflammation 2021;8:[Online First] I http://dx.doi.org/10.20517/2347-8659.2020.57 insubstantial: further work is needed in IP with and without small-intestinal-bacterial-overgrowth and including a non-fermentable sugar absorption test. Concentrations of markers of intestinal inflammation (faecal calprotectin) and bacterial translocation (circulating lipopolysaccharide-binding protein) appear not to change with time-sincediagnosis or IP severity. This is compatible with a pre-presentation insult. There are no longitudinal studies on inflammation or translocation to guide design of interventional studies. Neither are cut-points discriminant for IPfacets, or gradients prognostic for its evolution, defined. Conclusion: Intestinal inflammation and barrier function is a strategic junctional point in the hypothesis for the aetipathogenesis of IP.