MSACL Conference Schedule

Metabolomics Reveals Large Effect of Gut Microflora on Host Biochemistry and Subsequent Activation of a Host Response
Tue 4:00 PM - Session: Metabolomics
Eric Peters
Gut microflora (the microbiome) have been show to have a significant impact on human health. Untargeted metabolomics was used to investigate the effect of gut microbes on plasma biochemistry in a mouse model. Plasma from germ free mice was compared with wild type species using a novel combination of metabolomics methods to help broaden the scope of the profiling experiments. More than 100 plasma features were unique to wild type species, presumably resulting from bacterial metabolism. Additionally, at least ten percent of all shared features were seen to change in intensity by factors greater than 1.5-fold.

Three major effects of the microbiome were observed:

  1. endogenous mammalian metabolism is altered,
  2. unique bacterial metabolites are produced by the microbiome and can directly be detected in blood, and
  3. bacterial metabolites produce a host response via classical phase II drug metabolism pathways such as sulfation and glycine conjugation.
Two metabolic pathways were found to be particularly affected; namely, tryptophan/indole metabolism and the metabolism of phenyl compounds. For example, plasma levels of tryptophan and acetyl-tryptophan were reduced in wild type species, while several different indole-based compounds were only observed in wild type mice. Phenyl compounds generated in the gut by bacterial action were conjugated to produce sulfated species such as phenyl sulfate and p-cresol sulfate in the liver, and subsequently appear in plasma. Additionally, exogenous aromatic bacterial compounds such as benzoic, phenylacetic, and cinnamic acids are conjugated with glycine to produce hippuric acid, phenylacetylglycine, and cinnamoyl glycine, respectively.

These studies hint at the surprisingly large effect of the gut microbiome on plasma biochemistry, the overlap between bacterial and mammalian metabolism, and the fuzzy line between endogenous and exogenous.