Title : Metagenomic inquiry of human gut microbiome for gluten-degrading enzymes for celiac disease therapy
Abstract:
Celiac disease (CeD) is experiencing a notable surge in incidence across India. While the genetic predisposition—carrying the HLA-DQ2/DQ8 gene plays a role, not all genetically susceptible individuals develop the disease, pointing to other critical factors in CeD pathogenesis. Emerging research suggests that differences in gut microbiota may be key, with certain microbes in healthy individuals potentially transforming gluten, the primary environmental trigger, into a non-immunogenic form. Our innovative work explores the use of metagenomic data to identify gut microbial enzymes which degrade the harmful components of gluten, paving the way for novel therapeutic strategies to manage CeD.
Using advanced metagenomic analysis approaches combined with in silico filtering, we have identified two promising enzyme candidates with the potential to neutralize the immunogenic properties of gluten. These recombinant enzymes, validated at the molecular level and in CaCo-2 cell line, have demonstrated remarkable efficacy in reducing gliadin immunogenicity. Functional assays—including qPCR analysis of ZO-1 and occludin, confocal microscopy, TEER assay and IL-6 secretion measurement—confirm their ability to restore barrier integrity and reduce inflammatory responses.
Our next phase involves validating these promising enzymes in a preclinical mouse model, with the ultimate goal of translating this research into a pioneering therapeutic approach for CeD. By targeting the root cause of gluten immunogenicity, this research holds the potential to significantly remodel how CeD is managed and treated.