Reference : Systematic prediction of health-relevant human-microbial co-metabolism through a comp...
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
http://hdl.handle.net/10993/20709
Systematic prediction of health-relevant human-microbial co-metabolism through a computational framework
English
Heinken, Almut Katrin mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Thiele, Ines mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
2015
Gut Microbes
Landes Bioscience
6
2
120-130
Yes (verified by ORBilu)
International
1949-0976
1949-0984
Austin
TX
[en] human gut microbiome ; metabolic modeling ; host-microbiota interactions
[en] The gut microbiota is well known to affect host metabolic phenotypes. The systemic effects of the gut microbiota on host metabolism are generally evaluated via the comparison of germfree and conventional mice, which is impossible to perform for humans. Hence, it remains difficult to determine the impact of the gut microbiota on human metabolic phenotypes. We demonstrate that a constraint-based modeling framework that simulates “germfree” and “exgermfree”
human individuals can partially fill this gap and allow for in silico predictions of systemic human-microbial cometabolism. To this end, we constructed the first constraint-based host-microbial community model, comprising the most comprehensive model of human metabolism and 11 manually curated, validated metabolic models of commensals, probiotics, pathogens, and opportunistic pathogens. We used this host-microbiota model to predict potential metabolic host-microbe interactions under 4 in silico dietary regimes. Our model predicts that gut microbes
secrete numerous health-relevant metabolites into the lumen, thereby modulating the molecular composition of the body fluid metabolome. Our key results include the following: 1. Replacing a commensal community with pathogens caused a loss of important host metabolic functions. 2. The gut microbiota can produce important precursors of host hormone synthesis and thus serves as an endocrine organ. 3. The synthesis of important neurotransmitters is elevated in the presence of the gut microbiota. 4. Gut microbes contribute essential precursors for glutathione, taurine, and leukotrienes. This computational modeling framework provides novel insight into complex metabolic host-microbiota interactions and can serve as a powerful tool with which to generate novel, non-obvious hypotheses regarding host-microbe co-metabolism.
Luxembourg Centre for Systems Biomedicine (LCSB): Molecular Systems Physiology (Thiele Group)
ATTRACT program grant from the Luxembourg National Research Fund (FNR) to I.T. (FNR/A12/01)
http://hdl.handle.net/10993/20709
10.1080/19490976.2015.1023494
The gut microbiota is well known to affect host metabolic phenotypes. The systemic effects of the gut microbiota on host metabolism are generally evaluated via the comparison of germfree and conventional mice, which is impossible to perform for humans. Hence, it remains difficult to determine the impact of the gut microbiota on human metabolic phenotypes. We demonstrate that a constraint-based modeling framework that simulates “germfree” and “ex-germfree” human individuals can partially fill this gap and allow for in silico predictions of systemic human-microbial co-metabolism. To this end, we constructed the first constraint-based host-microbial community model, comprising the most comprehensive model of human metabolism and 11 manually curated, validated metabolic models of commensals, probiotics, pathogens, and opportunistic pathogens. We used this host-microbiota model to predict potential metabolic host-microbe interactions under four in silico dietary regimes. Our model predicts that gut microbes secrete numerous health-relevant metabolites into the lumen, thereby modulating the molecular composition of the body fluid metabolome. Our key results include the following: 1. Replacing a commensal community with pathogens caused a loss of important host metabolic functions. 2. The gut microbiota can produce important precursors of host hormone synthesis and thus serves as an endocrine organ. 3. The synthesis of important neurotransmitters is elevated in the presence of the gut microbiota. 4. Gut microbes contribute essential precursors for glutathione, taurine, and leukotrienes. This computational modeling framework provides novel insight into complex metabolic host-microbiota interactions and can serve as a powerful tool with which to generate novel, non-obvious hypotheses regarding host-microbe co-metabolism.

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