EXPLORING PANETH CELL DYSFUNCTION IN CROHN’S DISEASE PATIENTS

Abstract

 Paneth cells are critical epithelial regulators of intestinal homeostasis, antimicrobial defense, and microbiota composition. Their dysfunction has been increasingly implicated in the pathogenesis of Crohn’s disease (CD), yet the specific cellular, genetic, and microbial correlates of Paneth cell impairment remain underexplored. This study aimed to evaluate Paneth cell morphology, antimicrobial function, associated gene expression, and microbiota profiles in Crohn’s disease patients compared to healthy controls to better understand the role of Paneth cell dysfunction in disease progressionForty-six healthy controls and one hundred and twenty-two Crohn’s disease patients received ileal biopsy together with stool sample.  We counted for paneth cells, checked the granules and performed immunohistochemistry for both lysozyme and defensin.  The expression of NOD2 and ATG16L1 was studied using QRT-PCR.  Both the range of microbial organisms and dysbiosis were assessed with 16S rRNA sequencing.  Statistical analyses found that Paneth cell counts in Crohn’s disease patients were lower (mean 16.4) and more granule abnormalities were seen (in 42.7% of cases) than in the control group (21.8 with 18.3% abnormal granules).  Levels of lysozyme and defensin showed large declines in the sick group, where mean decreases were over 30%.  Higher than expected levels of NOD2 and ATG16L1 confirmed shared genetic risk factors seen in the literature.  Microbe analysis revealed lower diversity and more dysbiosis in the microbial profiles of CD patients and both factors were strongly connected to the lack of Paneth cells and not having enough antimicrobials.  The analysis found that less numerous Paneth cells in the tissue were tied to greater amounts of dysbiosis and the correlation matrices exposed important links between different cellular, molecular and microbial parameters.  Many factors lead to wrong function of paneth cells in Crohn's disease, including visual, genetic and bacterial changes in the body.  These outcomes indicate possible approaches for stabilizing the gut and show that Paneth cell evaluation should be included in clinical testing.