The metabolic phenotype of any complex organism is dependent on a
complex series of host and gut microbial gene (microbiome) interactions with diet.
The microbiome itself can be affected by environmental factors such as stress,
exposure to xenobiotics, lifestyle, and alterations in the mammalian-microbial-metabolic
axis are associated with changes in disease factors.
To understand further the impact of the commensal microbiota on the host
metabolism, germ-free (GF) animals, inoculated with individual bacterial strains or
complex microbiota, and conventional mice were characterised using 1H NMR
spectroscopy and UPLC-MS-based metabolic profiling approaches, and by recording
the physiological and immunological parameters.
Higher systemic level of (D)-3-hydroxybutyrate and lower levels of circulating
VLDL were observed in GF compared to conventional animals, indicating that the
absence of gut microbiota stimulated lipolysis while it inhibited hepatic lipogenesis.
Subsequently, the best inoculation procedure was obtained by inoculating single
bacterial strains into individual animals followed by allowing the animals to exchange
their microbes. Metabolic fingerprints showed that a 9 bacteria community is more
able to regulate lipoprotein and circulating lipid levels compared to a 3 bacteria
community. The origin of the inocula (mouse or human) impacts differently on the
host metabolism since humanised mice were strongly disturbed (higher plasma
triglyceride level) and displayed metabolic profiles similar to GF mice. Conversely,
mouse-associated animals were physiologically, immunologically and metabolically
similar to conventional animals. Finally, metabolic profiles and gut microbiota
composition were statistically regressed and helped to identify specific bacteria, such
as Ruminococcus lactaris and Faecalibacterium prausnitzii, and their putative role in
the host homeostasis.
To conclude, these results confirmed the influence of gut microbes on the
host physiology and metabolism. This PhD thesis provides new insights into the role
of gut bacteria to understand the microbial-related mechanisms that participate in the
host lipid metabolism, potentially leading to development of obesity.