화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.513, No.2, 426-433, 2019
Bacterial beta-glucuronidase alleviates dextran sulfate sodium-induced colitis in mice: A possible crucial new diagnostic and therapeutic target for inflammatory bowel disease
Objective: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are devastating diseases of the gut. At present, all the treatments are mainly targeting symptoms like inflammation. The disease remains regarded as incurable, largely due to lacking of knowledge on its etiology. Our previous studies suggested that impaired inactivation of digestive proteases by deconjugated bilirubin in experimental colitis, thus bacterial beta-glucuronidase for catalyzing the reaction, may have played critical role in the pathogenesis of IBD. Methods: We first analyzed beta-glucuronidase activity in gut tissue and feces of mice by a colitis model. Then the effect of beta-glucuronidase on experimental colitis was investigated in detail by administration of beta-glucuronidase (from E. coli) and fecal material transplantation to mice with 3% DSS in drinking water for 7 days. Results: Mice with colitis showed unchanged activity of beta-glucuronidase in colon tissue but decreased activity in feces. Treatment with bacterial beta-glucuronidase at 100 U or above alleviated DSS-induced colitis as demonstrated by the less body weight loss, less disease activity score, increased expression of tight junction proteins and decreased gut permeability, decreases in MPO, TNF-alpha, IL-10, TLR-4 and MyD88, and increase in IL-10 and I kappa B3 alpha in gut, restored fecal beta-glucuronidase and gut microbiota along with decreases in fecal digestive proteases. Transplantation of fecal material from control to colitis mice showed similar effects as treatment with beta-glucuronidase. Conclusions: Bacterial beta-glucuronidase showed strong inhibition on colitis along with the reduction in fecal digestive proteases, which may be a crucial diagnostic and therapeutic target for IBD. (C) 2019 Published by Elsevier Inc.