Panorganismal gut microbiome-host metabolic crosstalk.
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.
Martin
Francois-Pierre J
FP
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
Sprenger
Norbert
N
Yap
Ivan K S
IK
Wang
Yulan
Y
Bibiloni
Rodrigo
R
Rochat
Florence
F
Rezzi
Serge
S
Cherbut
Christine
C
Kochhar
Sunil
S
Lindon
John C
JC
Holmes
Elaine
E
Nicholson
Jeremy K
JK
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