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Immunological effects of Lactobacillus johnsonii N6.2 in healthy adults: A double‐blind, randomized trial
Author(s) -
Lorca Graciela L,
Marcial Guillermo,
Ford Amanda,
Gezan Salvador,
Perry Daniel,
Haller Michael,
Wasserfall Clive,
Brusko Todd,
Atkinson Mark,
Gonzalez Claudio,
Dahl Wendy
Publication year - 2017
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.31.1_supplement.454.2
Subject(s) - immunology , biology , immunophenotyping , flow cytometry , type 1 diabetes , medicine , endocrinology , diabetes mellitus
The intestinal 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. L. johnsonii N6.2 mitigated the onset of T1D when administered to Biobreeding diabetes‐prone rats by altering 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 immunological response 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 8 CFU or placebo), and 4‐week wash‐out. Blood samples were collected and analyzed throughout the study. Leukocyte subpopulations were assessed at baseline, treatment, and washout by immunophenotyping using flow cytometry and serum blood markers were quantified by ELISAs. Consumption of the L. johnsonii N6.2 did not affect the B cells, dendritic cells or regulatory T cells subsets. However, significant changes were observed in Monocytes, Natural Killer cells, T cells, T effector and follicular helper T cells in the L. johnsonii group. Specifically, the administration of L. johnsonii N6.2 increased the population of activated effector T cells, Th1 (CD45RO + , CD183 + , CD196 − ) after 8 weeks of treatment, an effect that was maintained after the wash‐out period (12 weeks). Based on these results, the concentrations of IL2, IL6, TNFa, INFa, IFNg, sCD25 (IL2Ra), C reactive protein, insulin and IgA were quantified in blood samples. It was found that the concentrations of IgA increased significantly over the time in the L. johnsonii group while no changes were observed for the others. In this study, we identified several biomarkers as a result of L. johnsonii N6.2 consumption in healthy subjects. The results of this pilot study provide a solid foundation for an investigation into prevention of T1D onset by L. johnsonii N6.2 in an at‐risk human population. Support or Funding Information These studies were funded by grants from the JDRF (1‐INO‐2014‐176‐A‐V to GLL and a Career Development Award 2‐2012‐280 to TMB) and grants from the National Institutes of Health P01 AI42288 (to MAA and TMB.).