Safety of Lactobacillus Reuteri DSM 17938 in Healthy Children 2-5 Years of Age.
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ABSTRACT:
SUBMITTER: Kosek MN
PROVIDER: S-EPMC6557701 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Safety of Lactobacillus Reuteri DSM 17938 in Healthy Children 2-5 Years of Age.
Kosek Margaret N MN Peñataro-Yori Pablo P Paredes-Olortegui Maribel M Lefante John J Ramal-Asayag Cesar C Zamora-Babilonia Marcelo M Meza-Sanchez Graciela G Oberhelman Richard A RA
The Pediatric infectious disease journal 20190801 8
Probiotics are increasingly used for diarrhea, but studies under the Food and Drug Administration and Investigational New Drug program are few. We conducted a phase-one placebo-controlled study of Lactobacillus reuteri DSM 17938 under Investigational New Drug program in 60 children 2-5 years of age (41 L. reuteri, 19 placebos) in a resource-constrained community in Peru. No differences in objective data on adverse events were noted, although some differences based on subjective parental reports ...[more]
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Project description: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 × 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.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.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 NCT00922727.
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Project description:The introduction of a strain or consortium has often been considered as a potential solution to restore microbial ecosystems. Extensive research on the skin microbiota has led to the development of probiotic products (with live bacterial strains) that are likely to treat dysbiosis. However, the effects of such introductions on the indigenous microbiota have not yet been investigated. Here, through a daily application of Lactobacillus reuteri DSM 17938 on volunteers' forearm skin, we studied in vivo the impact of a probiotic on the indigenous skin bacterial community diversity using Terminal-Restriction Fragment Length Polymorphism (T-RFLP) for 3 weeks. The results demonstrate that Lactobacillus reuteri DSM 17938 inoculum had a transient effect on the indigenous community, as the resilience phenomenon was observed within the skin microbiota. Moreover, Lactobacillus reuteri DSM 17938 monitoring showed that, despite a high level of detection after 2 weeks of application, thereafter the colonization rate drops drastically. The probiotic colonization rate was correlated significantly to the effect on the indigenous microbial community structure. These preliminary results suggest that the success of probiotic use and the potential health benefits resides in the interactions with the human microbiota.
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Project description:The effectiveness of Lactobacillus reuteri DSM 17938 (L. reuteri) for the management of acute gastroenteritis (AGE) has been recently questioned. We performed a systematic review to update evidence on L. reuteri for treating AGE in children. We searched MEDLINE, EMBASE, the Cochrane Library databases, and additional data sources from January 2016 (end of search for our 2016 systematic review) to August 2019. The primary outcomes were stool volume and duration of diarrhea. Four RCTs were included. None of them evaluated stool volume. Compared with placebo or no treatment, L. reuteri reduced diarrhea duration (four RCTs, n = 347, mean difference, MD -0.87 days, 95% CI [-1.43, -0.31]). L. reuteri use was also associated with a reduced duration of hospitalization (three RCTs, n = 284, MD -0.54 days, 95% CI [-1.09, 0.0]). The small effect sizes of limited clinical relevance and methodological limitations of the included trials should be noted when interpreting these findings.
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Project description:INTRODUCTION:Administration of some probiotics appears to reduce the risk of antibiotic-associated diarrhoea (AAD). The effects of probiotics are strain-specific, thus, the efficacy and safety of each probiotic strain should be established separately. We aim to assess the effects of Lactobacillus reuteri DSM 17938 administration for the prevention of diarrhoea and AAD in children. METHODS AND ANALYSIS:A total of 250 children younger than 18?years treated with antibiotics will be enrolled in a double-blind, randomised, placebo-controlled trial in which they will additionally receive L. reuteri DSM 17938 at a dose 108 colony-forming units or an identically appearing placebo, orally, twice daily, for the entire duration of antibiotic treatment. The primary outcome measures will be the frequencies of diarrhoea and AAD. Diarrhoea will be defined according to 1 of 3 definitions: (1) ?3 loose or watery stools per day for a minimum of 48?hours during antibiotic treatment; (2) ?3 loose or watery stools per day for a minimum of 24?hours during antibiotic treatment; or (3) ?2 loose or watery stools per day for a minimum of 24?hours during antibiotic treatment. AAD will be diagnosed in cases of diarrhoea, defined clinically as above, caused by Clostridium difficile or for otherwise unexplained diarrhoea (ie, negative laboratory stool tests for infectious agents). ETHICS AND DISSEMINATION:The Bioethics Committee approved the study protocol. The findings of this trial will be submitted to a peer-reviewed paediatric journal. Abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER:NCT02871908.
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Project description:Human breast milk (HBM) may have beneficial effects on Lactobacillus reuteri DSM 17938 (LR 17938) -mediated immunomodulation. We aimed to determine the effects of HBM on proliferation of LR 17938 in vitro and its associated proteins and metabolites in culture, in order to provide mechanistic insights into the health benefits of LR 17938. LR 17938 was cultured anaerobically in MRS bacterial culture media, HBM (from 6 mothers), and 2 types of cow-milk formula. The colony-forming unit (CFU) was calculated to evaluate LR 17938 growth. Sixteen-hour-fermented supernatants were used for metabolomics, and bacterial lysates were used for proteomics analysis. We found that growth of LR 17938 was 10 times better in HBM than in formula. We detected 261/452 metabolites upregulated when LR 17938 cultured in HBM compared to in formula, mainly participating in the glyoxylate cycle (succinate), urea cycle (citrulline), methionine methylation (N-acetylcysteine), and polyamine synthesis (spermidine). The significantly up-regulated enzymes were also involved in the formation of acetyl-CoA in the glyoxylate cycle and the antioxidant N-acetylcysteine. In conclusion, HBM enhances the growth of LR 17938 compared to formula and promotes LR 17938-associated metabolites that relate to energy and antioxidant status, which may be linked to the physiological effects of L. reuteri.
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