title: Lactobacillus johnsonii inhibits indoleamine 2,3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats.
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.
authors.affiliation: Department of Microbiology and Cell Science, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida 32610-3610, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Valladares
authors.forename: Lora
authors.initials: L
authors.lastname: Bojilova
authors.forename: Anastasia H
authors.initials: AH
authors.lastname: Potts
authors.forename: Evan
authors.initials: E
authors.lastname: Cameron
authors.forename: Christopher
authors.initials: C
authors.lastname: Gardner
authors.forename: Graciela
authors.initials: G
authors.lastname: Lorca
authors.forename: Claudio F
authors.initials: CF
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism*; D007778:Lactobacillus / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011913:Rats, Inbred BB; D012701:Serotonin / Q000097:blood; D014364:Tryptophan / Q000037:antagonists & inhibitors*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007211:Indoles; D012701:Serotonin; D007737:Kynurenine; C030374:indole; D014364:Tryptophan; D006861:Hydrogen Peroxide