INTRODUCTION: The members of the human gut microbiota contain a large diversity of genes, including antimicrobial resistance genes (ARGs) known as the gut resistome. The resistome is susceptible to alterations when compositional changes occur in the fecal and 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 (patients experiencing gastrointestinal symptoms, but with no endoscopic or histologic signs of IBD at inclusion, and no evidence of IBD during follow-up, were classified as symptomatic non-IBD 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 were 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), four AMR gene families and 14 AMR drug classes. The use of 5-ASA was associated with abundance changes for 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 changes in abundance of five drug classes (Zoliflodacin, lincosamide, macrolide, streptogramin and tetracycline). Corticosteroids were associated with changes in the ARO terms sul2, OXA beta-lactamase AMR gene family, and three drug classes (carbapenem, glycylcycline, and triclosan). CONCLUSIONS: All IBD medication groups were found to be associated with significant abundance changes within the fecal resistome between inclusion and follow-up time points, where corticosteroid treatment resulted in less resistance in the microbiota compared to in the persons not treated with corticosteroids (either 5-Aminosalicylic Acid or Biological treatments).
Keywords: AMR; IBD; Microbiome; Resistome.