Safety and Tolerability of Lactobacillus reuteri DSM 17938 and Effects on Biomarkers in Healthy Adults: Results from a Randomized Masked Trial
Open Access
- 6 September 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (9), e43910
- https://doi.org/10.1371/journal.pone.0043910
Abstract
There are few carefully-designed studies investigating the safety of individual probiotics approved under Investigational New Drug policies. 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. Forty healthy adults were randomized to a daily dose of 5×108 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. 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 µg/g (IQR 24–127 µg/g) vs. 17 µg/g (IQR 11–26 µg/g), p = 0.03, although values remained in the normal clinical range (0–162.9 µg/g). LR vials retained >108 CFUs viable organisms/ml. 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. Clinical Trials.gov NCT00922727This publication has 40 references indexed in Scilit:
- Lactobacillus reuteristrains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-κB signaling in the intestineAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2012
- Nutrient Metal Sequestration by Calprotectin Inhibits Bacterial Superoxide Defense, Enhancing Neutrophil Killing of Staphylococcus aureusCell Host & Microbe, 2011
- Multisite Comparison of High-Sensitivity Multiplex Cytokine AssaysClinical and Vaccine Immunology, 2011
- Quantitative Validation and Comparison of Multiplex Cytokine KitsSLAS Discovery, 2010
- Performance of serum-supplemented and serum-free media in IFNγ Elispot Assays for human T cellsCancer Immunology, Immunotherapy, 2009
- CD4+ T Cells and Lactobacillus casei Control Relapsing Colitis Mediated by CD8+ T CellsThe Journal of Immunology, 2009
- Validation and comparison of two multiplex technologies, Luminex® and Mesoscale Discovery, for human cytokine profilingJournal of Immunological Methods, 2009
- Lactobacillus reuteri(American Type Culture Collection Strain 55730) Versus Simethicone in the Treatment of Infantile Colic: A Prospective Randomized StudyPEDIATRICS, 2007
- Multiplexed Analysis of Biomarkers Related to Obesity and the Metabolic Syndrome in Human Plasma, Using the Luminex-100 SystemClinical Chemistry, 2005
- WHO cytokine standardization: facilitating the development of cytokines in research, diagnosis and as therapeutic agentsJournal of Immunological Methods, 1998