STIMULATION OF MUCOSAL INFLAMMATORY ACTIVITY BY THE NORMAL FECAL FLORA IN A RAT MODEL OF COLITIS

Bacteria and their products stimulate inflammatory responses and may p lay a role in the pathogenesis of inflammatory bowel diseases. We inve stigated interactions between fecal flora and injured colonic mucosa u sing the trinitrobenzenesulfonic acid model of colitis in the rat. Fir st, we tested the effects of broad-spectrum antibiotics administered a t different times after induction of colitis. Second, in rats pretreat ed with antibiotics, we studied the effects of reintroduction of fecal flora on the release of inflammatory mediators and on the morphology of colonic lesions. Antibiotics reduced colonic lesion scores when sta rted on day I after induction of colitis, but had no significant effec t when started on day 7. In antibiotic-treated rats, intracolonic admi nistration of a suspension of fecal contents 6 h after induction of co litis enhanced mucosal inflammatory activity and aggravated lesion sco res. This effect was not observed when the suspension was administered 3 days after induction. Sonication of the suspension inhibited bacter ial growth in aerobic and anaerobic cultures, and abolished its effect on colonic inflammation. In this model, bacteria of the common flora stimulate inflammatory activity and play a role in the induction of co lonic mucosal lesions.