Limitation of amino acid availability by bacterial populations during enhanced colitis in IBD mouse model
Author:
Richie Tanner G.1ORCID,
Heeren Leah1,
Kamke Abigail1,
Monk Kourtney1,
Pogranichniy Sophia1,
Summers Trey1,
Wiechman Hallie1,
Ran Qinghong1,
Sarkar Soumyadev1,
Plattner Brandon L.2,
Lee Sonny T. M.1ORCID
Affiliation:
1. Division of Biology, Kansas State University, Manhattan, Kansas, USA
2. Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas, USA
Abstract
ABSTRACT
Members of the Enterobacteriaceae and
Enterococcus
are associated with persistent gut inflammation due to rapid colonization combined with pathogenic tendencies. Here, we investigated the functions of gut microbial populations resulting in persistent gut inflammation. In this study, we utilized the IL-10 knockout mouse model and induced colitis using dextran sulfate sodium (2%) after development. Dams during gestation were provided cefoperazone to induce vertically transmitted dysbiosis in the pups that were monitored in this study. We characterized the dysbiotic gut microbial community and potential crosstalk of these microbes, and host gene expression changes to identify bacterial populations and potential functions that were involved in gut inflammation. We isolated Enterobacteriaceae populations from mice to validate the utilization of sulfur-containing amino acids. Members of Enterobacteriaceae and
Enterococcus
were highly detected in inflamed mice. Enterobacteriaceae populations containing L-cysteine dioxygenase were strongly correlated with the upregulation of host gene
CSAD
, responsible for cysteine breakdown. We observed that bacterial isolates from dysbiotic mice displayed increased growth rates when supplemented with L-cysteine, highlighting the use of sulfur metabolism. Our results show that microbial populations use alternate metabolisms and sequester host nutrients for growth, associated with inflammation in the gut.
IMPORTANCE
Inflammatory bowel disease is associated with an increase in Enterobacteriaceae and Enterococcus species; however, the specific mechanisms are unclear. Previous research has reported the associations between microbiota and inflammation, here we investigate potential pathways that specific bacteria populations use to drive gut inflammation. Richie et al. show that these bacterial populations utilize an alternate sulfur metabolism and are tolerant of host-derived immune-response products. These metabolic pathways drive host gut inflammation and fuel over colonization of these pathobionts in the dysbiotic colon. Cultured isolates from dysbiotic mice indicated faster growth supplemented with L-cysteine, showing these microbes can utilize essential host nutrients.
Funder
HHS | NIH | National Institute of General Medical Sciences
Kansas IDeA Network of Biomedical Research Excellence
KSU | Johnson Cancer Research Center, Kansas State University
Kansas Intellectual and Developmental Disabilities Research Center
Molecular Regulation of Cell Development and Differentiation
NIH S10 High-end Instrumentation Grant
KU | Frontiers Clinical and Translational Science Institute, University of Kansas
Publisher
American Society for Microbiology
Subject
Computer Science Applications,Genetics,Molecular Biology,Modeling and Simulation,Ecology, Evolution, Behavior and Systematics,Biochemistry,Physiology,Microbiology