Safety And Tolerability Of Lactobacillus Reuteri Dsm 17938 And Effects On Biomarkers In Healthy Adults: Results From A Randomized Masked Trial

Background: There are few carefully-designed studies investigating the safety of individual probiotics approved under Investigational New Drug policies.Objectives: The primary aim of this prospective, double-blind placebo-controlled trial was to investigate if daily treatment of adults with Lactobacillus reuteri DSM 17938 (LR) for 2 months is safe and well-tolerated. Our secondary aim was to determine if LR treatment has immune effects as determined by regulatory T cell percentages, expression of toll-like receptors (TLR)-2 and -4 on circulating peripheral blood mononuclear cells (PMBCs), cytokine expression by stimulated PBMC, and intestinal inflammation as measured by fecal calprotectin.Methods: Forty healthy adults were randomized to a daily dose of 5 x 10(8) CFUs of LR (n = 30) or placebo (n = 10) for 2 months. Participants completed a daily diary card and had 7 clinic visits during treatment and observation.Results: There were no severe adverse events (SAEs) and no significant differences in adverse events (AEs). There were no differences in PBMC subclasses, TLRs, or cytokine expression after treatment. The probiotic-treated group had a significantly higher fecal calprotectin level than the placebo group after 2 months of treatment: 50 mu g/g (IQR 24-127 mu g/g) vs. 17 mu g/g (IQR 11-26 mu g/g), p = 0.03, although values remained in the normal clinical range (0-162.9 mu g/g). LR vials retained >10(8) CFUs viable organisms/ml.Conclusions: LR is safe and well tolerated in adults, without significant changes in immunologic markers. There was a small but significant increase in fecal calprotectin, perhaps indicating some element of immune recognition at the intestinal level.