Understanding host and microbial metabolites in functional gut disorders : a thesis presented in particle fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Palmerston North, New Zealand
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Date
2021
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Massey University
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Abstract
Interactions between diet, host, and the gut microbiome can result in beneficial or detrimental effects on human health. Functional gut disorders (FGDs) are an example of the negative effects of these interactions. However, an understanding of the mechanisms behind FGDs remains unknown. Metabolomics is a powerful tool to understand possible mechanisms. It was hypothesised that key metabolite groups in faecal samples would differ between or within FGD subtypes and healthy controls reflective of mechanistic perturbations. This PhD aimed to characterise the metabolite profile of FGD individuals (functional constipation (FC), IBS-constipation (IBS-C), functional diarrhoea (FD), IBS-diarrhoea (IBS-D), IBS-mixed (IBS-M)) and healthy controls. The concentration of faecal bile acids and plasma amino acids were quantified to ascertain changes in known metabolites associated with FGDs. The faecal metabolome was characterised to potentially identify wider perturbations, and this was then integrated with dietary intake, plasma metabolome abundance and faecal microbiota composition for a systems biology analysis.
Constipation (FC + IBS-C) and diarrhoea (FD + IBS-D) were combined to determine differences between healthy controls and disease states. Faecal bile acid concentrations differed between all FGD participants and healthy controls. In the combined analysis of the diarrhoea (FD+IBS-D) and constipation (FC+IBS-C) groups, the diarrhoea group had a higher concentration of bile acids than the constipation group or healthy control group. The concentration of plasma amino acids did not differ between FGD participants and healthy controls. Furthermore, analysis of key amino acid groups showed that only the concentration of branched chain amino acids were different between all subtypes and healthy controls.
Characterisation of faecal polar, semi-polar and lipid metabolites showed a differential relative abundance of some polar and semi-polar metabolites (e.g., riboflavin, nicotinic acid) between diarrhoea and healthy control groups, and constipation and healthy control groups. Substantial changes in the abundance of some lipids (e.g., ceramides, triglycerides) were evident between constipation and healthy control groups, and diarrhoea and healthy control groups.
Integration of the faecal metabolome with other datasets (faecal microbiome, plasma metabolome, dietary intake) showed the faecal metabolome and microbiome separated healthy controls from constipation or diarrhoea. Additionally, differential positive and negative correlations were observed between faecal lipids (triglycerides and diglycerides) and microbial species (Firmicutes and Bacteroidetes).
This PhD thesis presents novel insights into the metabolite signature characterising FGD participants and healthy controls and provides directions for future research.
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Keywords
Gastrointestinal system, Motility, Disorders, Microbial metabolites, Feces