1 JCHR (2021) 11, 1-11 Journal of Chemical Health Risks www.jchr.org Review of Recent Advances in Treatment of Celiac Disease Using Enzymatic Gluten Degradation Mansooreh Hooshiyar 1 , Gholam Hossein Ebrahimi Pour 1 , Mohammad Rostami-Nejad *2 , Fahimeh Sadat gholam- Mostafaei 2 , Kaveh Baghaei 2 , Alireza Emadi 3 , Vahid Khalaj *4 1 Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran 2 Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3 Deputy of Research and Technology, Semnan University of Medical Sciences, Semnan, Iran 4 Fungal Biotechnology Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran (Received: 22 August 2020 Accepted: 17 April 2021) KEYWORDS Celiac disease; Enzymatic gluten degradation, Aspergillus niger; Prolyl endopeptidase; Treatment; Glutenase; Wheat; Enzyme therapy ABSTRACT: Celiac disease (CD), a chronic inflammatory disorder, is triggered by the ingestion of gluten peptide. Wheat gluten contains gliadins and glutenins fractions, where gliadin peptides are the main cause of CD and nonceliac gluten sensitivity development. Keeping a strict gluten-free diet is the only effective treatment for CD. In recent years, lactic acid bacterial and fungal prolyl endopeptidases (PEP) have been proposed as the sources of proteolytic enzymes for the complete elimination of gluten peptides, and have also proved as a potential common therapeutic agent for CD treatment. Considering these indications, a special focus was devoted to AN-PEP-secreted PEP. Herein, we review the proteolytic enzymes produced by microorganisms, especially by the fungal strain, Aspergillus niger (AN), and discuss its beneficial properties against toxic effects of α-gliadin digestion in affected patients. The present review reveals the importance of proteolytic proteases in industrial applications; from an economic perspective, AN-PEP protease is an appropriate choice for making high-quality gluten-free products. Abbreviations AN, Aspergillus niger; AO, Aspergillus flavus var. oryzae; CD, celiac disease; FM, Flavobacterium meningosepticum; GFD, gluten-free diet; LAB, lactic acid bacteria; MX, Myxococcus xanthus; RM, Rothia mucilaginosa; SC, Sphingomonas capsulata; TG2, human tissue transglutaminase; GLUFR, Friendly Gluten; ssdf, special sourdough-fermented; INTRODUCTION Celiac disease (CD) is a multifactorial and chronic inflammatory disorder with global prevalence of about 1% [1]. This disorder occurs in genetically susceptible cases and is mostly linked to the ingestion of gluten from the wheat, barley, and rye. Glutenins and gliadins are core factors affecting the CD development and non-celiac gluten sensitivity. Evidence has disclosed that the susceptibility to CD arises from the intestinal damage by interactions between specific gliadin oligopeptides and the human leukocyte antigen (HLA)-DQ2 (or DQ8) molecules [2], as well as macrophages, dendritic cells, and B-cells *Corresponding author: m.rostamii@gmail.com ; v_khalaj@yahoo.com (M. Rostami-Nejad; Vahid Khalaj ) DOI: 10.22034/jchr.2021.1907514.1167