Probiotic intervention reduces stressor-enhanced anxiety-like behavior and significantly reduces circulating IL-6 at the peak of infection. Mice were restrained for 1 day and then orally challenged with C. rodentium. Restraint continued for 6 days postchallenge, during which the drinking water was supplemented with either VEH or L. reuteri, beginning 1 day prior to restraint. Prior to sacrifice, mice were tested by the open field test and recorded for 5 min. Locomotion was quantified by the total number of lines crossed and the amount of time spent in the center of the open field. (A) There were no changes in the total number of lines crossed in either stressor-exposed group. Sample sizes were as follows: n = 12 (CON/VEH), n = 12 (CON/L. reuteri), n = 6 (RST/VEH), and n = 4 (RST/L. reuteri). (B) There was an increase in anxiety-like behavior, as evidenced by a reduction in the time spent in the center of the open field, in VEH-treated, stressor-exposed mice, which was restored with L. reuteri treatment. *, P < 0.05 between CON/VEH and RST/VEH groups as assessed by Student's t test with the Bonferroni correction factor as a post hoc test. Sample sizes were as follows: n = 18 (CON/VEH), n = 18 (CON/L. reuteri), n = 9 (RST/VEH), and n = 9 (RST/L. reuteri). Cytokine levels were determined by a Bio-Plex assay. (C) Circulating IL-1β was reduced by stressor exposure on day 12 postchallenge, and L. reuteri failed to modulate this reduction. *, ANOVA main effect for group (CON versus RST; P = 0.01). Sample sizes were as follows: n = 13 (CON/VEH), n = 11 (CON/L. reuteri), n = 7 (RST/VEH), and n = 7 (RST/L. reuteri). (D) Circulating IL-6, however, was significantly increased by stressor exposure in VEH-treated mice on day 12 postchallenge. Probiotic intervention with L. reuteri reduced stressor-enhanced circulating IL-6 levels. *, P < 0.001 between CON/VEH and RST/VEH groups. Student's t test with the Bonferroni correction factor was used as a post hoc test. Sample sizes were as follows: n = 14 (CON/VEH), n = 13 (CON/L. reuteri), n = 7 (RST/VEH), and n = 6 (RST/L. reuteri).