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PMID: 18197175 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model.

Molecular systems biology ·Vol. 4 ·2008-00-00 ·Pages 157

Martin FP, Wang Y, Sprenger N, Yap IK, Lundstedt T, Lek P, Rezzi S, Ramadan Z, van Bladeren P, Fay LB, Kochhar S, Lindon JC, Holmes E, Nicholson JK

Abstract

The transgenomic metabolic effects of exposure to either Lactobacillus paracasei or Lactobacillus rhamnosus probiotics have been measured and mapped in humanized extended genome mice (germ-free mice colonized with human baby flora). Statistical analysis of the compartmental fluctuations in diverse metabolic compartments, including biofluids, tissue and cecal short-chain fatty acids (SCFAs) in relation to microbial population modulation generated a novel top-down systems biology view of the host response to probiotic intervention. Probiotic exposure exerted microbiome modification and resulted in altered hepatic lipid metabolism coupled with lowered plasma lipoprotein levels and apparent stimulated glycolysis. Probiotic treatments also altered a diverse range of pathways outcomes, including amino-acid metabolism, methylamines and SCFAs. The novel application of hierarchical-principal component analysis allowed visualization of multicompartmental transgenomic metabolic interactions that could also be resolved at the compartment and pathway level. These integrated system investigations demonstrate the potential of metabolic profiling as a top-down systems biology driver for investigating the mechanistic basis of probiotic action and the therapeutic surveillance of the gut microbial activity related to dietary supplementation of probiotics.

MeSH Terms
Animals Bile Acids and Salts/analysis,chemistry Cell Compartmentation Chromatography, Liquid Fatty Acids, Volatile/blood,chemistry,urine Feces/microbiology Female Gastrointestinal Tract/chemistry,drug effects,microbiology Host-Parasite Interactions Humans Ileum/chemistry,drug effects Infant, Newborn Liver/drug effects,metabolism,microbiology Mass Spectrometry Metagenome/drug effects Mice Models, Animal Models, Biological Nuclear Magnetic Resonance, Biomolecular Principal Component Analysis Probiotics/pharmacology Protons Species Specificity Symbiosis/drug effects Tissue Extracts
Chemicals
Bile Acids and Salts Fatty Acids, Volatile Protons Tissue Extracts
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Martin Francois-Pierre J
Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College London, London, UK.
Wang Yulan
Sprenger Norbert
Yap Ivan K S
Lundstedt Torbjörn
Lek Per
Rezzi Serge
Ramadan Ziad
van Bladeren Peter
Fay Laurent B
Kochhar Sunil
Lindon John C
Holmes Elaine
Nicholson Jeremy K
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Article Info
Journal
Molecular systems biology
Abbr.
Mol Syst Biol
ISSN
1744-4292
DOI
10.1038/msb4100190
Published
2008-00-00
Epub
2008-00-15
Pages
157
Language
English
Region
England
NLM ID
101235389
PMCID
PMC2238715
Subset
IM
Grants
NHLBI NIH HHS · R01 HL071950 · United States
NHLBI NIH HHS · 5-R01-HL 71950-2 · United States
External Links
PubMed source DOI: 10.1038/msb4100190 PMC Full Text View journal details
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