Phase I: Safety and Tolerance of Lactobactocillus reuteri in Adults

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DESCRIPTION (provided by applicant): A Phase 1 Study will be conducted in order to determine safety and tolerability of L. reuteri DSM 17938, 10^8 CFU daily, in treating healthy adults. It is required by the FDA that we conduct a Phase 1 study showing the safety and efficacy of L. reuteri (in sunflower oil) drops in adults before conducting our infant colic study. The study includes a single dose 5 x 10^8, 5 drops daily of L. reuteri; and we will determine the effects, if any, in subjects receiving recommended manufactured dose. This study will be conducted over a one year period with the first two months being the most critical. During the first two months, patients will attend 7 scheduled appointments and maintain bi-weekly diaries, serum chemistries, and 3 and 6-month follow-up visits. Adverse events will be recorded. We have received final IRB approval of this project on 4/24/2009 (#08-0266). Results of this study are expected to show safety and tolerability and will enable the FDA to approve studies of L. reuteri in infants with colic (and other illnesses). The long term goals are to elucidate mechanisms of intestinal disease in children ages (0 - 18 years) and identify viable treatments. Relevant to the NIH mission, this proposal is designed as a Phase I Study in Healthy Adults testing the efficacy and tolerability of L. reuteri. But in addition, we will determine effects of LR on baseline and stimulated levels of a cytokine panel in peripheral blood mononuclear cells (PBMC) after stimulation by PMA plus ionomycin; TLR2 and TLR4 expression in human PBMC; number of Treg cells in human PBMC; and fecal calprotectin assay. We also hope to conduct future research on probiotic therapeutic interventions in gastrointestinal diseases. Much more information is needed to characterize the complex gut microflora-immune system in association with gastrointestinal conditions in newborns such as colic. Public Health Relevance: Our studies would provide evidence for safety of probiotics, more specifically l. reuteri. Evidence could identify the early onset of gastrointestinal conditions, such as Irritable Bowel Syndrome. L. reuteri could possibly assist in the prevention of acute diarrhea and allergic disease. We will demonstrate if treatment of l. reuteri in healthy adults shows efficacy and tolerability. Also if physiologically, l. reuteri has an autoimmune effect on the human system, more specifically toll like receptors and cytokines identifying the specific strain as pro-inflammatory or anti-inflammatory. A mechanism could be identified for a particular probiotic and its effects on the gastrointestinal system.