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A Double‐Blind, Randomized Human Trial To Evaluate The Safety, Tolerability, And Host Response To Lactobacillus johnsonii N6.2
Author(s) -
Lorca Graciela L,
Marcial Guillermo G.,
Ford Amanda L,
Haller Michael J,
Gonzalez Claudio F,
Dahl Wendy J
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb299
Subject(s) - placebo , tolerability , probiotic , irritable bowel syndrome , medicine , feces , gastroenterology , enterococcus faecium , immunology , lactobacillus , biology , physiology , adverse effect , microbiology and biotechnology , bacteria , pathology , antibiotics , alternative medicine , genetics
Several human trials have successfully showed oral Lactobacillus supplementation alleviates symptoms of disorders ranging from asthma to irritable bowel syndrome. It is increasingly clear that the gut environment may play a central role in the development of Type 1 Diabetes (T1D); however, the use of bacteria to alleviate the onset of this disease has been restricted to studies in rodent models. To date, the ability of a Lactobacillus probiotic to prevent T1D onset in humans has not been evaluated. We isolated and characterized L. johnsonii N6.2, which mitigated the onset of T1D when administered to Biobreeding diabetes‐prone rats. We determined that L. johnsonii N6.2 alters the activity of intestinal indoleamine 2,3‐dioxygenase‐1 (IDO), correlating with a Th17 bias in the mesenteric lymph nodes of animals protected from T1D onset. Translating this work toward the prevention of T1D in humans required a pilot study in healthy individuals. We performed a human trial to evaluate the safety, tolerability, and general response to consumption of this microorganism in healthy individuals (n=42; F=30, M=12; 23.2±5.5 y). The 13‐week study was divided into three phases: 1‐week pre‐baseline, 8‐week intervention (1 capsule/d of L. johnsonii N6.2 at 10 10 CFU or placebo), and 4‐week wash‐out. Blood and fecal samples were collected and analyzed throughout the study. Stool samples were plated to determine transit survival of L. johnsonii N6.2 . The administration of the probiotic did not modify the hemogram and chemistry profiles of participants suggesting general safety. The levels of tryptophan metabolites were determined in serum throughout the study. It was found that in participants who consumed L. johnsonii, the serum levels of kynurenine were decreased while increased amounts of tryptophan were observed. These results are in agreement with observations in rodent models of T1D. The results obtained from this pilot study will provide a solid foundation for the approval of an investigation into prevention of T1D onset by L. johnsonii N6.2 consumption in an at‐risk human population. Support or Funding Information Juvenile Diabetes Research Foundation