The probiotic, Lactobacillus salivarius subsp. salivarius 433118 (UCC118), was investigated for its potential to attenuate colitis, modulate immune responses and alter intestinal barrier dysfunction in two different mouse models of inflammatory bowel disease (IBD). Following oral treatment with UCC118, faecal microbial analysis indicated that viable intact bacteria reached the colons of interleukin (IL)-10-/- mice and dextran sodium sulphate (DSS)-treated mice. Neither prophylactic nor therapeutic UCC118 treatment significantly prevented or attenuated inflammation in either model. In all studies, the probiotic-treated mice had comparable cytokine responses as vehicle-treated animals. Mannitol permeability was increased across colonic mucosae mounted in Ussing chambers from DSS-treated mice, but not in IL-10 -/- mice. However, colonic mucosae from UCC118-treated mice had unchanged transepithelial electrical resistance (TEER) values and mannitol fluxes compared to controls. In two different mouse colitis models examined under a range of histological and functional criteria, the data therefore suggest that this Lactobacillus subsp. has limited potential as a prophylactic or therapeutic treatment for inflammatory bowel disease. While several studies have shown therapeutic activity for this probiotic in mouse models of IBD, our data suggest that there are inter-study variables in formulation, study design, animal models and assessment criteria that may impact on interpretation of probiotic efficacy. © 2007 Springer Science+Business Media, LLC.