Limitation of amino acid availability by bacterial populations during enhanced colitis in IBD mouse model

Abstract

The microbiota has profound influence on the host through interactions with the immune system early in host development. These interactions are crucial in understanding complex autoimmune diseases, such as Inflammatory Bowel Disease (IBD). Here, we examined how specific groups of microbes in dysbiotic mice impacted outcomes of colitis, host immune response, gene expression, and microbial functional changes. Vertically transmitted dysbiotic pups received fecal microbiota transplantation (FMT) from control mice, at 2, 3, and 8 weeks after birth. After 23 weeks, remaining mice were supplemented with 2.5% dextran sulfate sodium to induce colitis. Colon histology revealed mice receiving FMT displayed less colon inflammation than mice with no gavage. We assembled 190 non-redundant Metagenome-Assembled Genomes (MAGs) from pup fecal content and highlighted microbial community differences in FMT mice compared to dysbiotic groups. Enterococcus sp. and Enterobacteriaceae members were highly detected in dysbiotic mice only. These MAGs shared a large number of antimicrobial resistance genes as well as several virulence factors including a T6SS along with multiple inflammation inducing metabolic pathways. The Enterobacteriaceae sp. displayed the ability to uptake and utilize cysteine and taurine for sulfur metabolism, in addition to utilizing the host immune response production of nitrate and nitrite as energy sources. Here, we find that potentially pathogenic microbes in the dysbiotic gut have the metabolic capability to compete with the host for sulfur-containing amino acids as well as host derived nitrate and nitrite to further inflame the gut, and worsening IBD symptoms.