Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways
Edited by Todd R. Klaenhammer, North Carolina State University, Raleigh, NC, and approved August 13, 2010 (received for review January 29, 2010)
Abstract
Probiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function through largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy adults to probiotics, we obtained transcriptomes in an intervention study after a double-blind placebo-controlled cross-over design. In the mucosa of the proximal small intestine of healthy volunteers, probiotic strains from the species Lactobacillus acidophilus, L. casei, and L. rhamnosus each induced differential gene-regulatory networks and pathways in the human mucosa. Comprehensive analyses revealed that these transcriptional networks regulate major basal mucosal processes and uncovered remarkable similarity to response profiles obtained for specific bioactive molecules and drugs. This study elucidates how intestinal mucosa of healthy humans perceives different probiotics and provides avenues for rationally designed tests of clinical applications.
Data Availability
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE18741).
Acknowledgments
We thank J. Jansen and M. Grootte Bromhaar (Wageningen University) for excellent microarray hybridizations, Roger Bongers and Bert van de Bunt for preparing the freeze-dried bacterial preparations used during the interventions, Iris van Swam for excellent technical support in QPCR analyses (NIZO Food Research), and Willem M. de Vos (Wageningen University) for his unrelenting support for this work and the many constructive discussions. P.v.B. was supported by the BioRange program of the Netherlands Bioinformatics Centre, which is supported by a BSIK grant through the Netherlands Genomics Initiative. The work of G.H. and M.B. is supported by the “Besluit Subsidies Investeringen Kennisinfrastructuur” (BSIK) program Netherlands Genomics Initiative and the Innovative Research Program Genomics.
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Information & Authors
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Published in
Cover image: Pictured is a selection of microbes discussed in the Microbes and Health Sackler Colloquium, which explores the complex interdependence between microbes and their human hosts. See the introductory article by Jeffrey I. Gordon and Todd R. Klaenhammer on pages 4513–4515. Top row: Bacteroides fragilis; Lactobacillus salivarius UCC118; and Bifidobacterium longum subspecies infantis. Middle row: Lactobacillus reuteri associated with the stomach epithelium of a mouse; mucus overlying the intestinal epithelium; and Roseburia species. Bottom row: Roseburia species; segmented filamentous bacterium in the mouse colon; and Bacteroides thetaiotaomicron. Images courtesy of: Top row: Sarkis K. Mazmanian (California Institute of Technology); Paul W. O'Toole (University College, Cork); and David A. Mills (University of California, Davis). Middle row: G. W. Tannock (University of Otago); Gunnar C. Hansson (University of Gothenburg); and Karen P. Scott (University of Aberdeen). Bottom row: Karen P. Scott (University of Aberdeen); Fredrik Bäckhed (University of Gothenburg); and Jeffrey I. Gordon, John Heuser, Eric Martens, and Robyn Roth (Washington University in St. Louis).
Proceedings of the National Academy of Sciences
Vol. 108 | No. supplement_1
March 15, 2011
March 15, 2011
PubMed: 20823239
Classifications
Data Availability
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE18741).
Submission history
Published online: September 7, 2010
Published in issue: March 15, 2011
Keywords
Acknowledgments
We thank J. Jansen and M. Grootte Bromhaar (Wageningen University) for excellent microarray hybridizations, Roger Bongers and Bert van de Bunt for preparing the freeze-dried bacterial preparations used during the interventions, Iris van Swam for excellent technical support in QPCR analyses (NIZO Food Research), and Willem M. de Vos (Wageningen University) for his unrelenting support for this work and the many constructive discussions. P.v.B. was supported by the BioRange program of the Netherlands Bioinformatics Centre, which is supported by a BSIK grant through the Netherlands Genomics Initiative. The work of G.H. and M.B. is supported by the “Besluit Subsidies Investeringen Kennisinfrastructuur” (BSIK) program Netherlands Genomics Initiative and the Innovative Research Program Genomics.
Notes
This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Microbes and Health,” held November 2–3, 2009, at the Arnold and Mabel Beckman Center of the National Academies of Sciences and Engineering in Irvine, CA. The complete program and audio files of most presentations are available on the NAS Web site at http://www.nasonline.org/SACKLER_Microbes_and_Health.
This article is a PNAS Direct Submission.
Authors
Competing Interests
The authors declare no conflict of interest.
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