Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes

Abstract

To characterize the impact of gut microbiota on host metabolism, we investigated the multicompartmental metabolic profiles of a conventional mouse strain (C3H/HeJ) (n¼5) and its germfree (GF) equivalent (n¼5). We confirm that the microbiome strongly impacts on the metabolism of bile acids through the enterohepatic cycle and gut metabolism (higher levels of phosphocholine and glycine in GF liver and marked higher levels of bile acids in three gut compartments). Furthermore we demonstrate that (1) well-defined metabolic differences exist in all examined compartments between the metabotypes of GF and conventional mice: bacterial co-metabolic products such as hippurate (urine) and 5-aminovalerate (colon epithelium) were found at reduced concentrations, whereas raffinose was only detected in GF colonic profiles. (2) The microbiome also influences kidney homeostasis with elevated levels of key cell volume regulators (betaine, choline, myoinositol and so on) observed in GF kidneys. (3) Gut microbiota modulate metabotype expression at both local (gut) and global (biofluids, kidney, liver) system levels and hence influence the responses to a variety of dietary modulation and drug exposures relevant to personalized health-care investigations.

Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet

“…This effect was also observed in KK-Ay mice, which showed increased levels of CA, DCA, TCA and TDCA in liver and intestine, which were also observed in our study in cecal samples of C57J mice fed with a HFD (Watanabe et al, 2006). The patterns of TBAs can be modulated through diet, absence of bacteria, distinct microbiome community, BAs or farnesoid X receptors agonists (Claus et al, 2008;Li et al, 2010a;Swann et al, 2011;Watanabe et al, 2011). In this study, lower abundance of TBAs in cecum of C57N mice could also be explained through an increase in their deconjugation rate by specific gut bacteria that are using the sulfur-containing taurine as an energy source such as Enterobacteria or Bacteroides spp.…”

High-fat diet alters gut microbiota physiology in mice

“…Finally, the cecal HF metaproteome was characterized by three enzymes (glutaredoxin, alkyl hydroperoxide and thioredoxin reductase) involved in oxidative stress responses, which may reflect adaptation to an environment with altered redox potential (Xiao et al, 2010). Holmes et al (2012) have provided evidence that the gut microbiome influences host metabolic phenotypes, based primarily on NMR studies (Claus et al, 2008;Calvani et al, 2010). However, only few papers focused on the analysis of metabolites in intestinal content (Martin et al, 2010).…”

Gut bacteria–host metabolic interplay during conventionalisation of the mouse germfree colon

“…Nevertheless, the effects of the intestinal microbiota can be observed in diverse regions of the host. 'Top-down' systems biology using metabolic profiling of conventional mice revealed large, systemic effects of the microbial community on absorption, storage and metabolism of dietary compounds (Martin et al, 2007;Claus et al, 2008). These, and other studies, have demonstrated that host metabolism is responsive to intestinal-microbial metabolism, which provides complementary pathways for resorption and assimilation of dietary ingredients and drugs .…”