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

doi:10.1073/pnas.0809919106

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

^aTop Institute Food and Nutrition, PO Box 557, 6700 AN, Wageningen, The Netherlands;
^bCentre for Molecular and Biomolecular Informatics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands;
^cDepartment of Internal Medicine, Division of Gastroenterology, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands;
^dNIZO Food Research, PO Box 20, 6710 BA, Ede, The Netherlands;
^eLaboratory of Microbiology, Agrotechnology and Food Sciences, Wageningen University, Dreijenplein 10, 6703 HB, Wageningen, The Netherlands;
^fDepartment of Basic Veterinary Sciences, Agnes Sjobergin katu 2, FI-00014 University of Helsinki, Finland; and
^gNutrition, Metabolism, and Genomics Group, Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV, Wageningen, The Netherlands

↵¹P.v.B and F.J.T. contributed equally to this work.
Edited by Todd R. Klaenhammer, North Carolina State University, Raleigh, NC, and approved December 18, 2008 (received for review October 3, 2008)

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-κB-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.

Keywords:

Footnotes

³To whom correspondence should be addressed: E-mail: michiel.kleerebezem{at}nizo.nl
Author contributions: F.J.T., C.v.d.M., W.M.d.V., R.-J.M.B., and M.K. designed research; F.J.T. and S.v.H. performed research; P.v.B., P.J.d.G., and G.J.E.J.H. analyzed data; and P.v.B., G.J.E.J.H., and M.K. wrote the paper.
↵²Present address: Host–Microbe Interactomics, Animal Sciences, Wageningen University, PO Box 338, 6700 AH Wageningen, The Netherlands.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.