Journal Articles
Permanent URI for this collectionhttps://mro.massey.ac.nz/handle/10179/7915
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Item Integrated multi-omic and symptom clustering reveals lower-gastrointestinal disorders of gut-brain interaction heterogeneity(Taylor and Francis Group, 2026-12-31) Dowrick JM; Roy NC; Carco C; James SC; Heenan PE; Frampton CMA; Fraser K; Young W; Cooney J; Trower T; Keenan JI; McNabb WC; Mullaney JA; Bayer SB; Talley NJ; Gearry RB; Angeli-Gordon TRRome IV disorders of gut-brain interaction (DGBI) subtypes are known to be unstable and demonstrate high rates of non-treatment response, likely indicating patient heterogeneity. Cluster analysis, a type of unsupervised machine learning, can identify homogeneous sub-populations. Independent cluster analyses of symptom and biological data have highlighted its value in predicting patient outcomes. Integrated clustering of symptom and biological data may provide a unique multimodal perspective that better captures the complexity of DGBI. Here, integrated symptom and multi-omic cluster analysis was performed on a cohort of healthy controls and patients with lower-gastrointestinal tract DGBI. Cluster stability was assessed by considering how frequently pairs of participants appeared in the same cluster between different bootstrapped datasets. Functional enrichment analysis was performed on the biological signatures of stable DGBI-predominant clusters, implicating disrupted ammonia handling and metabolism as possible pathophysiologies present in a subset of patients with DGBI. Integrated clustering revealed subtypes that were not apparent using a singular modality, suggesting a symptom-only classification is prone to capturing heterogeneous sub-populations.Item Concentrations of Plasma Amino Acids and Neurotransmitters in Participants with Functional Gut Disorders and Healthy Controls(MDPI (Basel, Switzerland), 2023-02-20) James SC; Fraser K; Cooney J; Günther CS; Young W; Gearry RB; Heenan PE; Trower T; Keenan JI; Talley NJ; McNabb WC; Roy NC; Jang CAmino acids are important in several biochemical pathways as precursors to neurotransmitters which impact biological processes previously linked to functional gastrointestinal disorders (FGIDs). Dietary protein consumption, metabolic host processes, and the gut microbiome can influence the plasma concentration of amino acids and neurotransmitters, and their uptake by tissues. The aim of this analysis was to quantify 19 proteogenic and 4 non-proteogenic amino acids and 19 neurotransmitters (including precursors and catabolites, herein referred to as neurotransmitters) to ascertain if their circulating concentrations differed between healthy participants and those with FGIDs. Plasma proteogenic and non-proteogenic amino acids and neurotransmitters were measured using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry, respectively, from 165 participants (Rome IV: irritable bowel syndrome (IBS-constipation, IBS-diarrhea), functional constipation, functional diarrhea, and healthy controls). There were significant differences (p < 0.05) in pairwise comparisons between healthy controls and specific FGID groups for branched-chain amino acids (BCAAs), ornithine, and alpha-aminobutyric acid. No other significant differences were observed for the neurotransmitters or any other amino acids analyzed. Multivariate and bivariate correlation analyses between proteogenic and non-proteogenic amino acids and neurotransmitters for constipation (constipation (IBS-C and functional constipation) and phenotypes diarrhea (IBS-D and functional diarrhea)) and healthy controls suggested that associations between BCAAs, 5-hydroxytryptophan, and kynurenine in combination with tyrosine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylacetic acid and associations with gamma-aminobutyric acid, glutamate, asparagine, and serine are likely disrupted in FGID phenotypes. In conclusion, although correlations were evident between some proteogenic and non-proteogenic amino acids and neurotransmitters, the results showed minor concentration differences in plasma proteogenic and non-proteogenic amino acids, amino acid-derived metabolites, and neurotransmitters between FGID phenotypes and healthy controls.Item Concentrations of Fecal Bile Acids in Participants with Functional Gut Disorders and Healthy Controls(MDPI (Basel, Switzerland), 2021-09-09) James SC; Fraser K; Young W; Heenan PE; Gearry RB; Keenan JI; Talley NJ; Joyce SA; McNabb WC; Roy NC; Apidianakis Y; Agapiou ABile acids are metabolites involved in nutrient absorption and signaling with levels influenced by dietary intake, metabolic processes, and the gut microbiome. We aimed to quantify 23 bile acids in fecal samples to ascertain if concentrations differed between healthy participants and those with functional gut disorders. Fecal bile acids were measured using liquid chromatography-mass spectrometry (LC-MS) in the COMFORT (The Christchurch IBS cohort to investigate mechanisms for gut relief and improved transit) cohort of 250 participants with Rome IV IBS (IBS-constipation (C), IBS-diarrhea (D), IBS-mixed (M)), functional gut disorders (functional constipation (FC), functional diarrhea (FD)) and healthy controls (FC n = 35, FD n = 13, IBS-C n = 24, IBS-D n = 52, IBS-M n = 29, and control n = 97). Dietary information was recorded to ascertain three-day dietary intake before fecal samples were collected. Fecal bile acid concentrations, predominantly primary bile acids, were significantly different between all functional gut disorder participants and healthy controls (CDCA p = 0.011, CA p = 0.003) and between constipation (FC + IBS-C) and diarrhea (FD + IBS-D) groups (CDCA p = 0.001, CA p = 0.0002). Comparison of bile acids between all functional groups showed four metabolites were significantly different, although analysis of combined groups (FC + IBS-C vs. FD + IBS-D) showed that 10 metabolites were significantly different. The bile acid profiles of FD individuals were similar to those with IBS-D, and likewise, those with FC were similar to IBS-C. Individuals with a diarrhea phenotype (FD + IBS-D) had higher concentrations of bile acids compared to those with constipation (FC + IBS-C). Bile acid metabolites distinguish between individuals with functional gut disorders and healthy controls but are similar in constipation (or diarrhea) whether classified as IBS or not.Item Increasing Evidence That Irritable Bowel Syndrome and Functional Gastrointestinal Disorders Have a Microbial Pathogenesis(Frontiers Media S.A., 2020-09-09) Carco C; Young W; Gearry RB; Talley NJ; McNabb WC; Roy NC; Ianiro GThe human gastrointestinal tract harbors most of the microbial cells inhabiting the body, collectively known as the microbiota. These microbes have several implications for the maintenance of structural integrity of the gastrointestinal mucosal barrier, immunomodulation, metabolism of nutrients, and protection against pathogens. Dysfunctions in these mechanisms are linked to a range of conditions in the gastrointestinal tract, including functional gastrointestinal disorders, ranging from irritable bowel syndrome, to functional constipation and functional diarrhea. Irritable bowel syndrome is characterized by chronic abdominal pain with changes in bowel habit in the absence of morphological changes. Despite the high prevalence of irritable bowel syndrome in the global population, the mechanisms responsible for this condition are poorly understood. Although alterations in the gastrointestinal microbiota, low-grade inflammation and immune activation have been implicated in the pathophysiology of functional gastrointestinal disorders, there is inconsistency between studies and a lack of consensus on what the exact role of the microbiota is, and how changes to it relate to these conditions. The complex interplay between host factors, such as microbial dysbiosis, immune activation, impaired epithelial barrier function and motility, and environmental factors, including diet, will be considered in this narrative review of the pathophysiology of functional gastrointestinal disorders.