Duval, X. | Search bioRxiv

bioRxiv2025

Identification and Functional Characterization of Regulatory Variants in DPP9 Associated with COVID-19 Severity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a wide-range of clinical outcomes, which have been extensively studied through genome-wide association studies (GWAS). Starting from lead genetic variants associated with COVID-19 infection and severity, we identified a subset of non-coding candidate variants with potential regulatory functions. Using bioinformatics analysis and functional screening in three cell lines, we prioritized two DPP9 variants within a haplotype that increases the risk of severe COVID-19. This haplotype exhibited increased regulatory activity and altered transcription factor binding, suggesting its role in influencing COVID-19 severity through modulation of DPP9 expression in immune and lung cell types. The interest of our study lies in the functional characterization of regulatory variants responsible for the higher levels of DPP9 and lung damage observed in patients with severe COVID-19. These findings advance our understanding of genetic risk factors for COVID-19 and highlight functional SNPs that may guide future therapeutic research.

genetics↗

bioRxiv2017

Protection of the human gut microbiome from antibiotics

BackgroundAntibiotics are life-saving drugs but severely affect the gut microbiome with short term consequences including diarrhoea, Clostridium difficile infections and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers.\n\nMethodsWe performed a randomized controlled trial (ClinicalTrials.gov NCT02176005) in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in two parallel groups, with or without DAV132 co-administration. Two control goups of 8 volunteers each receiving DAV132 alone, or a non-active substitute, were added.\n\nResultsThe co-administration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex-vivo.\n\nConclusionsDAV132 was highly effective to protect the gut microbiome of moxifloxacin - treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments.

clinical trials↗