title: Panorganismal gut microbiome-host metabolic crosstalk.
abstract: Coevolution shapes interorganismal crosstalk leading to profound and diverse cellular and metabolic changes as observed in gut dysbiosis in human diseases. Here, we modulated a simplified gut microbiota using pro-, pre-, and synbiotics to assess the depth of systemic metabolic exchanges in mice, using a multicompartmental modeling approach with metabolic signatures from 10 tissue/fluid compartments. The nutritionally induced microbial changes modulated host lipid, carbohydrate, and amino acid metabolism at a panorganismal scale. Galactosyl-oligosaccharides reduced lipogenesis, triacylglycerol incorporation into lipoproteins and triglyceride concentration in the liver and the kidney. Those changes were not correlated with decreased plasma lipoproteins that were specifically induced by L. rhamnosus supplementation. Additional alteration of transmethylation metabolic pathways (homocysteine-betaine) was observed in the liver and the pancreas following pre- and synbiotic microbial modulation, which may be of interest for control of glucose metabolism and insulin sensitivity. Probiotics also reduced hepatic glycogen and glutamine and adrenal ascorbate with inferred effects on energy homeostasis, antioxidation, and steroidogenesis. These studies show the breadth and the depth of gut microbiome modulations of host biochemistry and reveal that major mammalian metabolic processes are under symbiotic homeostatic control.
authors.affiliation: Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, United Kingdom. francois-pierre.martin@rdls.nestle.com
authors.forename: Francois-Pierre J
authors.initials: FP
authors.lastname: Martin
authors.forename: Norbert
authors.initials: N
authors.lastname: Sprenger
authors.forename: Ivan K S
authors.initials: IK
authors.lastname: Yap
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bibiloni
authors.forename: Florence
authors.initials: F
authors.lastname: Rochat
authors.forename: Serge
authors.initials: S
authors.lastname: Rezzi
authors.forename: Christine
authors.initials: C
authors.lastname: Cherbut
authors.forename: Sunil
authors.initials: S
authors.lastname: Kochhar
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D055442:Metabolome; D054892:Metagenome; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D019936:Probiotics / Q000378:metabolism