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Lactobacillus johnsonii inhibits indoleamine 2,3‐dioxygenase and alters tryptophan metabolite levels in BioBreeding rats

  • 2013-01-09
  • The FASEB Journal 27(4)
    • Ricardo B. Valladares
    • Lora Bojilova
    • Anastasia H. Potts
    • E. Cameron
    • Christopher L. Gardner
    • G. Lorca
    • Claudio F. Gonzalez

Abstract

In our previous work, we found that feeding Lactobacillus johnsonii to BioBreeding diabetes-prone (BBDP) rats decreased the incidence of diabetes development. The aim of this study was to investigate host pathways affected by L. johnsonii, with specific focus on the rate-limiting enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO). Suspensions of L. johnsonii or an equal volume of vehicle were orally administered to BBDP rats. Tissue IDO was investigated using quantitative RT-PCR and Western blot, whereas tryptophan, kynurenine, and 5-hydroxytryptamine (5-HT) concentrations were quantified by HPLC and ELISA. IDO activity was also investigated using L. johnsonii culture cell-free supernatant (CFS) with affinity-purified IDO and HT-29 intestinal epithelial cells. L. johnsonii feeding resulted in a 17% reduction in serum kynurenine compared with that in vehicle-fed controls, correlating with a 1.4-fold elevation in 5-HT levels. H₂O₂ produced by L. johnsonii abolished IDO activity in vitro, and L. johnsonii feeding resulted in a 3.9-fold increase in ileum lumen H₂O₂. L. johnsonii CFS significantly reduced IDO activity in HT-29 intestinal epithelial cells (47% reduction) compared with that in vehicle-treated controls, an effect abolished by catalase treatment. These data support the role of H₂O₂ in commensal bacteria-host interactions and highlight the influence of commensal bacteria-derived H₂O₂ on host physiology.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Lactobacillus johnsonii LJ09Increased Serotonin LevelsBeneficial
Moderate
Lactobacillus johnsonii LJ09Reduced Diabetes IncidenceBeneficial
Moderate
Lactobacillus johnsonii LJ09Reduced Serum Kynurenine LevelsBeneficial
Small
Lactobacillus johnsonii VPro 33Increased Serotonin LevelsBeneficial
Moderate
Lactobacillus johnsonii VPro 33Reduced Diabetes IncidenceBeneficial
Moderate
Lactobacillus johnsonii VPro 33Reduced Indoleamine 2,3-Dioxygenase ActivityBeneficial
Moderate
Lactobacillus johnsonii VPro 33Reduced Serum Kynurenine LevelsBeneficial
Small
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