INTRODUCTION: Preliminary results from our laboratory suggest that two strains of the probiotic bacteria Lactobacillus reuteri (rat-derived strain R2LC and human-derived strain ATCC PTA 4659) ameliorate DSS-induced colitis in mice. The underlying mechanisms involved in this protection are not known, but a link to intestinal resident immune cells can be assumed. The chemokine receptor CX3CR1 is expressed by circulating monocytes and by intestinal lamina propria resident cells believed to be macrophages and/or dendritic cells. Mice deficient in CX3CR1 (CX3CR1GFP/GFP) develop an aggravated DSS-induced colitis, suggesting a role of CX3CR1 in the maintenance of colonic homeostasis. AIM: To investigate if the protective mechanism of L. reuteri R2LC or ATCC PTA 4659 involve CX3CR1, colitis was induced by DSS in CX3CR1GFP/GFP mice. METHODS: Colitis was induced by 3% DSS in drinking water, administrated for 8 days to C57Bl/6 (wt) and CX3CR1GFP/GFP mice (C57Bl/6 background). Two groups from each strain were given L. reuteri R2LC or ATCC PTA 4659 by gavage once daily for 15 days in addition to DSS for the last 8 days. Disease severity was assessed through scoring of clinical symptoms (DAI, disease activity index) and histology scoring of H&E stained paraffin sections of distal colon. Multi-array measurements of the pro-inflammatory cytokines IL1-β, IL-6, TNF-α and mKC were also performed from colonic tissue samples. RESULTS: DAI was significantly reduced the last day of DSS treatment in the groups of wt mice treated with either strain of L. reuteri (2.9±0.17 for DSS (n = 20), 1.8±0.18 and 1.4±0.30 for DSS+4659 (n = 16) and DSS+R2LC (n = 11) respectively, SEM values). In the CX3CR1GFP/GFP mice DAI increased slightly more by DSS than in the wt, and the L. reuteri strains did not significantly reduce DAI. The levels of all proinflammatory cytokines measured in colon tissue were significantly higher in DSS treated CX3CR1GFP/GFP mice than in wt. Treatment with either strain of L. reuteri significantly reduced all cytokines in wt and CX3CR1GFP/GFP mice, with the exception of IL1-β in the latter group. Preliminary histology scoring demonstrates reduced inflammation in all L.reuteri treated groups. CONCLUSIONS: These results indicate that the protective role of the two different strains of L. reuteri on DSS-induced colitis is slightly reduced in CX3CR1GFP/GFP mice, compared to wt mice. Thus, the mechanism by which L.reuteri bacterial strains ameliorate colitis might involve CX3CR1. However, the possibility that the reduced protection by L. reuteri in the CX3CR1GFP/GFP mice is due to higher DAI and cytokine levels in these mice can not be excluded.