Exploring Metabolic Pathway Reconstruction and Genome-Wide Expression Profiling in Lactobacillus reuteri to Define Functional Probiotic Features

The genomes of four Lactobacillus reuteri strains isolated from human breast milk and the gastrointestinal tract have been recently sequenced as part of the Human Microbiome Project. Preliminary genome comparisons suggested that these strains belong to two different clades, previously shown to differ with respect to antimicrobial production, biofilm formation, and immunomodulation. To explain possible mechanisms of survival in the host and probiosis, we completed a detailed genomic comparison of two breast milk–derived isolates representative of each group: an established probiotic strain (L. reuteri ATCC 55730) and a strain with promising probiotic features (L. reuteri ATCC PTA 6475). Transcriptomes of L. reuteri strains in different growth phases were monitored using strain-specific microarrays, and compared using a pan-metabolic model representing all known metabolic reactions present in these strains. Both strains contained candidate genes involved in the survival and persistence in the gut such as mucus-binding proteins and enzymes scavenging reactive oxygen species. A large operon predicted to encode the synthesis of an exopolysaccharide was identified in strain 55730. Both strains were predicted to produce health-promoting factors, including antimicrobial agents and vitamins (folate, vitamin B12). Additionally, a complete pathway for thiamine biosynthesis was predicted in strain 55730 for the first time in this species. Candidate genes responsible for immunomodulatory properties of each strain were identified by transcriptomic comparisons. The production of bioactive metabolites by human-derived probiotics may be predicted using metabolic modeling and transcriptomics. Such strategies may facilitate selection and optimization of probiotics for health promotion, disease prevention and amelioration

Role of 5-HT 1A receptors in antidepressant-like effect of dichloromethane fraction of Kielmeyera coriacea in rats subjected to the forced swim test

Objective : We examined the involvement of 5-HT neurotransmission on the antidepressant-like effect of the dichloromethane (DcM) fraction of an extract from Kielmeyera coriacea stems. Materials and Methods : Male Wistar rats treated chronically (45 days, gavage) with the DcM fraction received an intradorsal raphe nucleus (DRN) microinjection of saline or 5-HT 1A receptor ligands and were evaluated in the forced swimming test (FST) and in the open-field test (OFT). Results : The DcM fraction (5.0 mg/kg) reduced immobility time in the FST without altering locomotion in the OFT. IntraDRN microinjection of the 5-HT 1A receptor agonist, (+)-8-OH-DPAT (0.10; 0.20 or 0.33 μg) increased immobility time and reduced locomotion at the higher dose whereas the 5-HT1A antagonists, (-)-pindolol (0.10; 0.20 or 0.40 μg) or WAY100635 (0.11; 0.22 or 0.43 μg) did not produce any effect in the behavioral tests. IntraDRN (+)-8-OH-DPAT (0.20 or 0.33 μg) in rats treated with the DcM fraction (5.0 mg/kg) blocked the changes in the immobility time or in locomotion produced by each drug. Intra-DRN (-)-pindolol (0.10 μg) or WAY100635 (0.43 μg) in rats treated with a subactive dose of the DcM fraction (4.0 mg/kg) synergistically reduced immobility time in the FST. Conclusion : The DcM fraction of Kielmeyera coriacea produced an antidepressant-like effect in the FST and interacted with 5-HT 1A receptor ligands. Activation of 5-HT 1A receptors into DRN by (+) 8-OH-DPAT produced detectable changes in the FST or in the OFT