A top‐down systems biology view of microbiome‐mammalian metabolic interactions in a mouse model

Abstract

Symbiotic gut microorganisms (microbiome) interact closely with the mammalian host's metabolism and are important determinants of human health. Here, we decipher the complex metabolic effects of microbial manipulation, by comparing germfree mice colonized by a human baby flora (HBF) or a normal flora to conventional mice. We perform parallel microbiological profiling, metabolic profiling by 1 H nuclear magnetic resonance of liver, plasma, urine and ileal flushes, and targeted profiling of bile acids by ultra performance liquid chromatography-mass spectrometry and short-chain fatty acids in cecum by GC-FID. Top-down multivariate analysis of metabolic profiles reveals a significant association of specific metabotypes with the resident microbiome. We derive a transgenomic graph model showing that HBF flora has a remarkably simple microbiome/metabolome correlation network, impacting directly on the host's ability to metabolize lipids: HBF mice present higher ileal concentrations of tauro-conjugated bile acids, reduced plasma levels of lipoproteins but higher hepatic triglyceride content associated with depletion of glutathione. These data indicate that the microbiome modulates absorption, storage and the energy harvest from the diet at the systems level.

Temporal variation selects for diet–microbe co-metabolic traits in the gut of Gorilla spp

“…Thus, these data may also provide hints to possible energy storage mechanisms in lowland gorillas, similar to those taking place in humans under high-caloric diets (Jones et al, 2008;Martin et al, 2007). Furthermore, fat deposition and storage are important evolutionary discriminant features between humans and non-human primates (Horrobin, 1999;Navarrete et al, 2011).…”

“…Although primate diets are typically very low in fat, fruits and seeds are important lipid sources Reiner et al, 2014). Indeed, taxa related to Coriobacteriaceae, Clostridium, Bifidobacterium and Lactobacillus, significantly enriched in lowland gorillas when ripe fruit was consumed, can also impact cholesterol and bile acid turnover in the colon (Gerard, 2010;Martin et al, 2007). This observation may explain the significant interactions observed between these taxa and abundances of coprostanol, cholestanol, hydrocholestane and ursodeoxycholic acid in the lowland gorilla metabolome.…”

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

“…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. (Ridlon et al, 2006;Martin et al, 2007). Moreover, the prominent opposite levels of all TBAs, comparing cecal and liver system, underlines a possible bacterial involvement.…”

Analysis of human urine metabolites using SPE and NMR spectroscopy

“…Tryptophan was also detected in this fraction. Fraction 3 contained 3-(3-methoxy-4-hydroxyphenyl) proprionate and indole-3-acetate [29] . It is noteworthy that lactate, which has high polarity and good water solubility, appeared in Fraction 4 but not in the earlier fraction probably owing to its intermolecular hydrogen bonding effects or some protein-binding effects.…”

“…With some spectral editing techniques [27] , one can also separate signals of metabolites according to their physical properties without separating samples [15,27,28] . With high resolution magic-angle spinning NMR and in vivo magnetic resonance techniques, the metabolites in biological tissues can also be analyzed which are exemplified in a number of studies of biological tissues such as the liver [9,19,[28][29][30] and intestine [31,32] .…”