Applying mass spectrometry-based assays to explore gut microbial metabolism and associations with disease

Clin Chem Lab Med. 2020 Apr 28;58(5):719-732. doi: 10.1515/cclm-2019-0974.

Abstract

The workings of the gut microbiome have gained increasing interest in recent years through the mounting evidence that the microbiota plays an influential role in human health and disease. A principal focus of this research seeks to further understand the production of metabolic by-products produced by bacteria resident in the gut, and the subsequent interaction of these metabolites on host physiology and pathophysiology of disease. Gut bacterial metabolites of interest are predominately formed via metabolic breakdown of dietary compounds including choline and ʟ-carnitine (trimethylamine N-oxide), amino acids (phenol- and indole-containing uremic toxins) and non-digestible dietary fibers (short-chain fatty acids). Investigations have been accelerated through the application of mass spectrometry (MS)-based assays to quantitatively assess the concentration of these metabolites in laboratory- and animal-based experiments, as well as for direct circulating measurements in clinical research populations. This review seeks to explore the impact of these metabolites on disease, as well as to introduce the application of MS for those less accustomed to its use as a clinical tool, highlighting pertinent research related to its use for measurements of gut bacteria-mediated metabolites to further understand their associations with disease.

Keywords: TMAO; biomarker; gut microbiome; mass spectrometry; short-chain fatty acids; uremic toxins.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacteria / chemistry
  • Bacteria / metabolism
  • Biomarkers / analysis
  • Chromatography, High Pressure Liquid
  • Cresols / analysis
  • Fatty Acids, Volatile / analysis
  • Fatty Acids, Volatile / metabolism
  • Gastrointestinal Microbiome*
  • Mass Spectrometry / methods*
  • Methylamines / analysis
  • Methylamines / metabolism
  • Uremia / pathology

Substances

  • Biomarkers
  • Cresols
  • Fatty Acids, Volatile
  • Methylamines
  • 4-cresol
  • trimethyloxamine