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Bacterial β-glucuronidase alleviates dextran sulfate sodium-induced colitis in mice: A possible crucial new diagnostic and therapeutic target for inflammatory bowel disease.

Abstract：

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 β-glucuronidase for catalyzing the reaction, may have played critical role in the pathogenesis of IBD. METHODS:We first analyzed β-glucuronidase activity in gut tissue and feces of mice by a colitis model. Then the effect of β-glucuronidase on experimental colitis was investigated in detail by administration of β-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 β-glucuronidase in colon tissue but decreased activity in feces. Treatment with bacterial β-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-α, IL-1β, TLR-4 and MyD88, and increase in IL-10 and IκBα in gut, restored fecal β-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 β-glucuronidase. CONCLUSIONS:Bacterial β-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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

He Y,Yu H,Ge Y,Li X,Jiang M,Liu Y,Li X,Wang Y,Guo M,Qin X,Wang X

doi

10.1016/j.bbrc.2019.03.196

subject

Has Abstract

pub_date

2019-05-28 00:00:00

pages

426-433

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)30603-5

journal_volume

513

pub_type

杂志文章

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Bacterial β-glucuronidase alleviates dextran sulfate sodium-induced colitis in mice: A possible crucial new diagnostic and therapeutic target for inflammatory bowel disease.