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Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance.

ABSTRACT: How do we acquire immune tolerance against food microorganisms and commensal bacteria that constitute the intestinal microbiota? We investigated this by stimulating the immune system of adults with commensal Lactobacillus plantarum bacteria. We studied the in vivo human responses to L. plantarum in a randomized double-blind placebo-controlled cross-over study. Healthy adults ingested preparations of living and heat-killed L. plantarum bacteria. Biopsies were taken from the intestinal duodenal mucosa and altered expression profiles were analyzed using whole-genome microarrays and by biological pathway reconstructions. Expression profiles of human mucosa displayed striking differences in modulation of NF-kappaB-dependent pathways, notably after consumption of living L. plantarum bacteria in different growth phases. Our in vivo study identified mucosal gene expression patterns and cellular pathways that correlated with the establishment of immune tolerance in healthy adults.

SUBMITTER: van Baarlen P

PROVIDER: S-EPMC2650163 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance.

van Baarlen Peter P Troost Freddy J FJ van Hemert Saskia S van der Meer Cindy C de Vos Willem M WM de Groot Philip J PJ Hooiveld Guido J E J GJ Brummer Robert-Jan M RJ Kleerebezem Michiel M

Proceedings of the National Academy of Sciences of the United States of America 20090203 7

How do we acquire immune tolerance against food microorganisms and commensal bacteria that constitute the intestinal microbiota? We investigated this by stimulating the immune system of adults with commensal Lactobacillus plantarum bacteria. We studied the in vivo human responses to L. plantarum in a randomized double-blind placebo-controlled cross-over study. Healthy adults ingested preparations of living and heat-killed L. plantarum bacteria. Biopsies were taken from the intestinal duodenal mu ...[more]

PMID: 19190178

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Project description:Probiotics have been rapidly developed for health promotion, but clinical validation of the effects on exercise physiology has been limited. In a previous study, Lactobacillus plantarum TWK10 (TWK10), isolated from Taiwanese pickled cabbage as a probiotic, was demonstrated to improve exercise performance in an animal model. Thus, in the current study, we attempted to further validate the physiological function and benefits through clinical trials for the purpose of translational research. The study was designed as a double-blind placebo-controlled experiment. A total of 54 healthy participants (27 men and 27 women) aged 20-30 years without professional athletic training were enrolled and randomly allocated to the placebo, low (3 × 1010 colony forming units (CFU)), and high dose (9 × 1010 CFU) TWK10 administration groups (n = 18 per group, with equal sexes). The functional and physiological assessments were conducted by exhaustive treadmill exercise measurements (85% VO2max), and related biochemical indices were measured before and after six weeks of administration. Fatigue-associated indices, including lactic acid, blood ammonia, blood glucose, and creatinine kinase, were continuously monitored during 30 min of exercise and a 90 min rest period using fixed intensity exercise challenges (60% VO2max) to understand the physiological adaptation. The systemic inflammation and body compositions were also acquired and analyzed during the experimental process. The results showed that TWK10 significantly elevated the exercise performance in a dose-dependent manner and improved the fatigue-associated features correlated with better physiological adaptation. The change in body composition shifted in the healthy direction for TWK10 administration groups, especially for the high TWK10 dose group, which showed that body fat significantly decreased and muscle mass significantly increased. Taken together, our results suggest that TWK10 has the potential to be an ergogenic aid to improve aerobic endurance performance via physiological adaptation effects.

Project description:BACKGROUND: Lactic acid bacteria are commonly marketed as probiotics based on their putative or proven health-promoting effects. These effects are known to be strain specific but the underlying molecular mechanisms remain poorly understood. Therefore, unravelling the determinants behind probiotic features is of particular interest since it would help select strains that stand the best chance of success in clinical trials. Bile tolerance is one of the most crucial properties as it determines the ability of bacteria to survive in the small intestine, and consequently their capacity to play their functional role as probiotics. In this context, the objective of this study was to investigate the natural protein diversity within the Lactobacillus plantarum species with relation to bile tolerance, using comparative proteomics. RESULTS: Bile tolerance properties of nine L. plantarum strains were studied in vitro. Three of them presenting different bile tolerance levels were selected for comparative proteomic analysis: L. plantarum 299 V (resistant), L. plantarum LC 804 (intermediate) and L. plantarum LC 56 (sensitive). Qualitative and quantitative differences in proteomes were analyzed using two-dimensional electrophoresis (2-DE), tryptic digestion, liquid chromatography-mass spectrometry analysis and database search for protein identification. Among the proteins correlated with differences in the 2-DE patterns of the bacterial strains, 15 have previously been reported to be involved in bile tolerance processes. The effect of a bile exposure on these patterns was investigated, which led to the identification of six proteins that may be key in the bile salt response and adaptation in L. plantarum: two glutathione reductases involved in protection against oxidative injury caused by bile salts, a cyclopropane-fatty-acyl-phospholipid synthase implicated in maintenance of cell envelope integrity, a bile salt hydrolase, an ABC transporter and a F0F1-ATP synthase which participate in the active removal of bile-related stress factors. CONCLUSIONS: These results showed that comparative proteomic analysis can help understand the differential bacterial properties of lactobacilli. In the field of probiotic studies, characteristic proteomic profiles can be identified for individual properties that may serve as bacterial biomarkers for the preliminary selection of strains with the best probiotic potential.

Dataset Information

Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance.

Publications

Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance.

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