Exploring Alterations in the Gut Resistome in Medically Treated Inflammatory Bowel Disease Patients

Introduction The members of the human gut microbiota contain a large diversity of antimicrobial resistance genes (ARGs), antiseptic resistance genes and heavy metal resistance genes, collectively known as the gut resistome. The resistome is susceptible to alterations when compositional changes occur in the gut microbiome. Medical treatment may affect members of the gut microbiota. This study hypothesizes that medication used by patients with inflammatory bowel disease (IBD) leads to an increased prevalence and diversity of ARGs in the gut and a corresponding change in the taxonomic composition of the fecal microbiome. Methods Fecal samples from 16 Crohn’s Disease (CD) and 16 Ulcerative Colitis (UC) patients, and 13 symptomatic controls were subjected to metagenomic sequencing. The samples were collected before initiation of IBD medication, and after one year of treatment. Patients were treated with 5- Amino Salicylic Acid, Biological treatment, and Corticosteroids, or a combination of the three. Resistance Gene Identifier Comprehensive Antibiotic Resistance Database (RGI CARD) and regression modelling was used to analyze the abundance and diversity changes in the ARGs and the taxonomy. Results We found significant associations with medicine use and abundance changes for eight resistance genes (Antibiotic Resistance Ontology (ARO) terms), three AMR gene families and 16 AMR drug classes. The use of 5-ASA was associated with abundance changes in tetracyclin inactivating enzyme tet(X6) and the efflux pump efpA. This medication was also associated with significant changes in the “pyrazinamide resistant rpsA” gene family and with six drug classes (cephamycin, diaminopyrimidine, mupirocin, penem , pyrazinamide and rifamycin). Biological treatment was associated with abundance of six drug classes (Zoliflodacin, lincosamide, macrolide, pactamycin, streptogramin and tetracycline). Corticosteroids was associated with changes in ARO terms sul2, OXA beta-lactamase AMR gene family, and four drug classes (carbapenem, glycylcycline, penam and triclosan). However, the changes in ARGs were not reflected in the taxonomic composition of the microbiome. Conclusions All IBD medication groups were found to be associated with significant abundance changes within the fecal gut resistome between inclusion and follow-up, where corticosteroid treatment resulted in less resistance in the microbiota compared to in the persons not treated with corticosteroids.