The pathophysiology of inflammatory bowel disease (IBD) involves the production of diverse lipid mediators, namely eicosanoid, lysophospholipids, and platelet-activating factor, in which phospholipase A2 (PLA2) is the key enzyme. Thus, it has been postulated that control of lipid mediators production by inhibition of PLA2 would be useful for the treatment of IBD. This hypothesis has been tested in the present study by examining the therapeutic effect of a novel natural probitic Bacillus subtilis PB6 (ATCC- PTA 6737). B. subtilis PB6 is found to secrete surfactins (cyclic lipopeptides) which have anti-bacterial potential. These surfactins inhibit PLA2, a rate-limiting enzyme involved in the arachidonic acid associated inflammatory pathway and could downregulate the inflammatory response by regulating the eicosanoid and cytokine pathways. With this concept, an experimental animal trial has been conducted in a rat model of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. The oral administration of PB6 suppresses the colitis as measured by mortality rate, changes in the weight gain, colon morphology and the levels of plasma cytokines. The animals treated orally with PB6 at 1.5 x 10(8) CFU/kg thrice daily from day 4 to 10 significantly improve gross pathology of the colon and regain the colon weight to normal (p < 0.05), compared to TNBS-induced positive control. The plasma levels of pro-inflammatory cytokines (TNF-alpha, 1L-1beta, IL-6 and IFN-gamma) are also significantly lowered (p < 0.05) and anti-inflammatory cytokine (IL-I0 and TGF-beta) significantly (p < 0.05) increased after the oral administration of PB6 on day 11. The present study supports the concept that PB6 inhibits PLA2 by the secreting surfactins. In a clinical investigation, it is found to be well tolerated by all the healthy volunteers.