Journal Articles

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    Characterisation of the Plasma and Faecal Metabolomes in Participants with Functional Gastrointestinal Disorders.
    (MDPI (Basel, Switzerland), 2024-12-16) Fraser K; James SC; Young W; Gearry RB; Heenan PE; Keenan JI; Talley NJ; McNabb WC; Roy NC; Fukui H
    There is evidence of perturbed microbial and host processes in the gastrointestinal tract of individuals with functional gastrointestinal disorders (FGID) compared to healthy controls. The faecal metabolome provides insight into the metabolic processes localised to the intestinal tract, while the plasma metabolome highlights the overall perturbances of host and/or microbial responses. This study profiled the faecal (n = 221) and plasma (n = 206) metabolomes of individuals with functional constipation (FC), constipation-predominant irritable bowel syndrome (IBS-C), functional diarrhoea (FD), diarrhoea-predominant IBS (IBS-D) and healthy controls (identified using the Rome Criteria IV) using multimodal LC-MS technologies. Discriminant analysis separated patients with the 'all constipation' group (FC and IBS-C) from the healthy control group and 'all diarrhoea' group (FD and IBS-D) from the healthy control group in both sample types. In plasma, almost all multimodal metabolite analyses separated the 'all constipation' or 'all diarrhoea' group from the healthy controls, and the IBS-C or IBS-D group from the healthy control group. Plasma phospholipids and metabolites linked to several amino acid and nucleoside pathways differed (p < 0.05) between healthy controls and IBS-C. In contrast, metabolites involved in bile acid and amino acid metabolism were the key differentiating classes in the plasma of subjects with IBS-D from healthy controls. Faecal lipids, particularly ceramides, diglycerides, and triglycerides, varied (p < 0.05) between healthy controls and the 'all constipation' group and between healthy controls and 'all diarrhoea' group. The faecal and plasma metabolomes showed perturbations between constipation, diarrhoea and healthy control groups that may reflect processes and mechanisms linked to FGIDs.
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    A period of 10 weeks of increased protein consumption does not alter faecal microbiota or volatile metabolites in healthy older men: a randomised controlled trial
    (Cambridge University Press on behalf of The Nutrition Society, 2020-07-02) Mitchell SM; McKenzie EJ; Mitchell CJ; Milan AM; Zeng N; D'Souza RF; Ramzan F; Sharma P; Rettedal E; Knowles SO; Roy NC; Sjödin A; Wagner K-H; O'Sullivan JM; Cameron-Smith D
    Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
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    A protocol combining breath testing and ex vivo fermentations to study the human gut microbiome
    (Elsevier Inc, 2021-03-19) Payling L; Roy NC; Fraser K; Loveday SM; Sims IM; Janssen PH; Hill SJ; Raymond LG; McNabb WC
    This protocol describes the application of breath testing and ex vivo fermentations to study the association between breath methane and the composition and functionality of the gut microbiome. The protocol provides a useful systems biology approach for studying the gut microbiome in humans, which combines standardized methods in human breath testing and fecal sampling. The model described is accessible and easy to repeat, but its relative simplicity means that it can deviate from human physiological conditions.
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    Adaptation of the infant gut microbiome during the complementary feeding transition
    (PLOS, 2022-07-14) McKeen S; Roy NC; Mullaney JA; Eriksen H; Lovell A; Kussman M; Young W; Fraser K; Wall CR; McNabb WC; xia Y
    The infant gut microbiome progresses in composition and function during the introduction of solid foods throughout the first year of life. The purpose of this study was to characterize changes in healthy infant gut microbiome composition, metagenomic functional capacity, and associated metabolites over the course of the complementary feeding period. Fecal samples were obtained at three 'snapshot' timepoints from infants participating in the 'Nourish to Flourish' pilot study: before the introduction of solid foods at approximately 4 months of age, after introducing solid foods at 9 months of age, and after continued diet diversification at 12 months of age. KEGG and taxonomy assignments were correlated with LC-MS metabolomic profiles to identify patterns of co-abundance. The composition of the microbiome diversified during the first year of life, while the functional capacity present in the gut microbiome remained stable. The introduction of solid foods between 4 and 9 months of age corresponded to a larger magnitude of change in relative abundance of sequences assigned to KEGG pathways and taxonomic assignments, as well as to stronger correlations with metabolites, compared to the magnitude of changes and number of correlations seen during continued diet diversification between 9 and 12 months of age. Changes in aqueous fecal metabolites were more strongly correlated with KEGG pathway assignments, while changes in lipid metabolites associated with taxonomic assignments, particularly between 9 and 12 months of age. This study establishes trends in microbiome composition and functional capacity occurring during the complementary feeding period and identifies potential metabolite targets for future investigations.
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    Effects of Defatted Rice Bran-Fortified Bread on the Gut Microbiota Composition of Healthy Adults With Low Dietary Fiber Intake: Protocol for a Crossover Randomized Controlled Trial
    (JMIR Publications, 2024-08-29) Ng HM; Maggo J; Wall CL; Bayer SB; McNabb WC; Mullaney JA; Foster M; Cabrera DL; Fraser K; Cooney J; Trower T; Günther CS; Frampton C; Gearry RB; Roy NC
    BACKGROUND: Inadequate dietary fiber (DF) intake is associated with several human diseases. Bread is commonly consumed, and its DF content can be increased by incorporating defatted rice bran (DRB). OBJECTIVE: This first human study on DRB-fortified bread primarily aims to assess the effect of DRB-fortified bread on the relative abundance of a composite of key microbial genera and species in fecal samples. Secondary outcomes include clinical (cardiovascular risk profile), patient-reported (daily bread consumption and bowel movement, gut comfort, general well-being, and total DF intake), biological (fecal microbiota gene abundances, and fecal and plasma metabolites), and physiome (whole-gut and regional transit time and gas fermentation profiles) outcomes in healthy adults with low DF intake. METHODS: This is a 2-armed, placebo-controlled, double-blinded, crossover randomized controlled trial. The study duration is 14 weeks: 2 weeks of lead-in, 4 weeks of intervention per phase, 2 weeks of washout, and 2 weeks of follow-up. Overall, 60 healthy adults with low DF intake (<18 g [female individuals] or <22 g [male individuals] per day) were recruited in Christchurch, New Zealand, between June and December 2022. Randomly assigned participants consumed 3 (female individuals) or 4 (male individuals) slices of DRB-fortified bread per day and then placebo bread, and vice versa. The DRB-fortified bread provided 8 g (female individuals) or 10.6 g (male individuals) of total DF, whereas the placebo (a matched commercial white toast bread) provided 2.7 g (female individuals) or 3.6 g (male individuals) of total DF. Before and after each intervention phase, participants provided fecal and blood samples to assess biological responses; completed a 3-day food diary to assess usual intakes and web-based questionnaires to assess gut comfort, general and mental well-being, daily bread intake, and bowel movement via an app; underwent anthropometry and blood pressure measurements; and drank blue food dye to assess whole-gut transit time. Additionally, 25% (15/60) of the participants ingested Atmo gas-sensing capsules to assess colonic gas fermentation profile and whole-gut and regional transit time. Mean differences from baseline will be compared between the DRB and placebo groups, as well as within groups (after the intervention vs baseline). For metabolome analyses, comparisons will be made within and between groups using postintervention values. RESULTS: Preliminary analysis included 56 participants (n=33, 59% female; n=23, 41% male). Due to the large dataset, data analysis was planned to be fully completed by the last quarter of 2024, with full results expected to be published in peer-reviewed journals by the end of 2024. CONCLUSIONS: This first human study offers insights into the prospect of consuming DRB-fortified bread to effectively modulate health-promoting gut microbes, their metabolism, and DF intake in healthy adults with low DF intake. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12622000884707; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383814. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59227.