Proteus mirabilis sp. intestinal microflora grow in a dextran sulfate sodium-rich environment

The pathogenic mechanisms responsible for inflammatory bowel disease, especially ulcerative colitis (UC), are poorly understood. As an animal model, the oral administration of dextran sulfate sodium (DSS) induces colitis, which exhibits several clinical and histological features similar to UC. However, the pathogenic factors responsible for DSS-induced colitis and above all, the intestinal microflora in this colitis remain unclear. Therefore, we investigated the relationships between DSS and the intestinal microflora in this study. First, the depolymerization of DSS in mouse feces was analyzed using a pyridylamino-labeling (PA-DSS) and HPLC system. Next, a bacteriological study of the fecal contents using DSS-rich media and subsequently a classification using 16S rRNA were performed. Surprisingly, DSS was depolymerized in mouse feces under aerobic conditions, not under anaerobic conditions. Several kinds of microflora were suggested to be involved in this depolymerization. In particular, Proteus mirabilis can grow in DSS-rich media and has an ability to desulfonate and depolymerize DSS. Then, we produced chemically-modified Mr 2500 DSS from native Mr 5000 DSS. This depolymerized Mr 2500 DSS was administered orally to mice and the colitis was evaluated histologically. The cytotoxicity of Mr 2500 DSS on Caco-2 cells was also investigated. Mr 2500 DSS induced weaker colitis in mice and weak cytotoxicity on Caco-2 cells as compared to Mr 5000 DSS. These findings give insight into the mechanisms responsible for DSS-induced colitis, especially with respect to the molecular mass of DSS.