Abstract
BACKGROUND: Iron deficiency anemia (IDA) is the most common extra-intestinal complication in inflammatory bowel disease (IBD). The persistence of iron deficiency in patients living with quiescent IBD remains poorly understood. Given the extensive body of research linking IBD pathogenesis to microbiome disruptions, it is hypothesized that alterations in the microbiota or immune responses may drive the persistence of IDA in quiescent Crohn's disease. This study aimed to determine whether changes in the gut microbiota or immune phenotypes contribute to IDA, while uncovering potential mechanisms driving IDA in quiescent disease. METHODS: This cross-sectional, descriptive, and analytical study utilized 141 samples from pediatric Crohn's disease patients with and without iron deficiency as well as healthy controls for initial 16S microbiome analysis and a smaller subset for Shotgun Metagenomics and immunologic analyses. Fecal and peripheral blood samples were obtained from the Jill Roberts Institute Live Cell Bank. RESULTS: While no major differences were observed in the overall gut microbiome composition between pediatric patients with quiescent Crohn's disease, with or without IDA, notable shifts in specific microbial strains were identified. Specifically, levels of Anaerobutyricum soehngenii and Alistipes shahii were significantly altered. Metagenomic analysis revealed an enrichment of pathways related to short-chain fatty acid metabolism and ascorbate degradation, indicative of functional change in these microbes. CONCLUSIONS: This is the first comprehensive microbiome analysis of quiescent pediatric Crohn's disease with concomitant IDA. The findings indicate modest but significant microbial strain-level differences and associated functional pathways, potentially implicating microbiota-mediated mechanisms in the persistence of IDA.