title: Safety and tolerability of Lactobacillus reuteri DSM 17938 and effects on biomarkers in healthy adults: results from a randomized masked trial.
abstract: BACKGROUND
  There are few carefully-designed studies investigating the safety of individual probiotics approved under Investigational New Drug policies.
  
  
  OBJECTIVE
  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 × 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 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 >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.
  
  
  BACKGROUND
  Clinical Trials.gov NCT00922727.
authors.affiliation: Department of Pediatrics, University of Texas Medical School at Houston, Houston, Texas, United States of America.
authors.forename: Nisha
authors.initials: N
authors.lastname: Mangalat
authors.forename: Yuying
authors.initials: Y
authors.lastname: Liu
authors.forename: Nicole Y
authors.initials: NY
authors.lastname: Fatheree
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ferris
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Van Arsdall
authors.forename: Zhongxue
authors.initials: Z
authors.lastname: Chen
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Rahbar
authors.forename: Wallace A
authors.initials: WA
authors.lastname: Gleason
authors.forename: Johana
authors.initials: J
authors.lastname: Norori
authors.forename: Dat Q
authors.initials: DQ
authors.lastname: Tran
authors.forename: J Marc
authors.initials: JM
authors.lastname: Rhoads
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D058645:Denaturing Gradient Gel Electrophoresis; D004311:Double-Blind Method; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D052200:Limosilactobacillus reuteri / Q000378:metabolism*; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019936:Probiotics / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D039841:Leukocyte L1 Antigen Complex; D051193:Toll-Like Receptors