Identifying biomarkers relevant to functional gastrointestinal disorders using a systems biology approach

Abstract

The links between food, gastrointestinal (GI) function and comfort, and brain function are at the forefront of nutritional research. A key part of the gut‐brain axis (GBA) is the GI microbiota. Animal studies show that normal development of the enteric and central nervous systems depends on microbial colonisation, which also modulates neurotransmitter abundance and activity, expression of genes linked to anxiety and synaptic plasticity, and prefrontal cortex myelination. Furthermore, GI bacteria can stimulate secretion of the neurotransmitter serotonin from enterocytes and some microbial tryptophan‐derived metabolites have neuroprotective and immune benefits. Irritable Bowel Syndrome (IBS) is a functional GI disorder characterised by chronic or recurrent abdominal discomfort mostly associated with changes in GI habit in the absence of a detectable organic cause. Several central and peripheral mechanisms initiate perturbations in GI motor and sensory functions and lead to IBS symptoms. Peripheral molecules, and associated pathway dysfunctions and altered tissue abundance or expression, are important to better define IBS and ultimately GI function and comfort. Global metabolite profiling across multiple sample types can provide biochemical fingerprints which can assist with understanding the underlying mechanisms. In a case‐control study, we aimed to identify microbial and host factors in plasma that provide mechanistic insights into functional GI disorders and increase the predictability of phenotypes for use in nutrition intervention studies. Individuals with functional GI symptoms (cases) or asymptomatic (controls) undergoing colonoscopy were recruited at Christchurch hospital and a subset of 102 plasma samples and 70 breath samples were measured. Plasma samples were subjected to biphasic extraction and liquid chromatography mass spectrometry analysis (LCMS) while breath volatiles were captured on carbon sorbent and subsequently analysed by gas chromatography MS (GCMS). LCMS analysis detected 491 polar, 458 semi‐polar and 768 non‐polar (lipids) metabolite features in plasma, while GCMS profiling yielded 37 volatile components in the breath. Significant partial least square discriminant analysis models were generated for all three LCMS plasma analyses (polar P=7.7e−5, Q2=0.46; semi‐polar P=5.5e−9, Q2=0.61; non‐polar P=4.5e−7, Q2=0.52) between the IBS phenotypes and the control subjects, with major perturbations observed in amino acid, bile acid and lipid metabolism. Breath volatile profiles revealed weak separations between the IBS phenotypes. The next steps include applying a systems biology approach using metabolomics (breath, plasma, faeces) and microbiota datasets of a larger cohort size to identify key pathways and biomarkers. Together with functional outcomes, these host‐microbial factors will provide new knowledge that can support the development of added‐value foods for improving GI function and comfort.Support or Funding InformationThis research was funded by the New Zealand Ministry of Business, Innovation and Employment as part of the High‐Value Nutrition National Science ChallengeThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.