Journal Articles
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Item Age-Dependent Increase in Small Intestinal Permeability and Sex-Dependent Absorptive Capacity in Cats (Felis catus)(Wiley-VCH GmbH, 2025-11-02) Patterson K; Bermingham EN; Fraser K; Bernstein D; Weidgraaf K; Shoveller AK; Thomas DGAge-associated changes in intestinal permeability and function have not been studied in domestic cats, leaving a key factor in the relationship between age and digestive health in cats unexplored. Due to factors not currently understood, mature and senior cats may experience a loss of fat and protein digestibility, along with a loss of body weight (BW), impacting lifespan and quality of life. Therefore, to establish the relationship between age and intestinal health, intestinal permeability and absorptive capacity were quantified in young and senior cats using a differential sugar absorption test (SAT) on cat plasma. A solution containing four different sized sugars was orally administered to 36 healthy mixed-breed domestic shorthair cats (male (n = 21) and female (n = 15)) split into two groups by age, young 2.40 ± 0.758 (n = 21) and senior 11.23 ± 1.896 (n = 15) years (mean ± SD). Blood was collected before and again 3 h after dosage and plasma was analysed using liquid chromatography mass-spectrometry (LC-MS). Intestinal permeability was higher (p = 0.004) in senior cats than young cats, and was not affected by sex (p = 0.288), sampling date (p = 0.652), or BW (p = 0.951). Absorptive capacity was higher (p = 0.033) in male cats than females, and was not affected by age class (p = 0.440), sampling date (p = 0.580), or BW (p = 0.652). In conclusion, intestinal permeability was higher in older cats and suggests age-related changes in intestinal barrier structure and function. These findings highlight the need to further consider increased intestinal permeability as a cause of reduced nutrient digestibility in older cats, offering a new target for interventions to enhance their health and well-being.Item Impact of Mānuka Honey on Symptoms and Quality of Life in Individuals With Functional Dyspepsia: Protocol for a Feasibility Randomized Controlled Trial(JMIR Publications, 2025-05-21) Ombasa L; Miller J; Ware L; Abbotts-Holmes H; Tang J; Gasser O; Fraser K; Bayer S; Kemp R; Costello R; Highton A; Evans J; Merry T; Schultz M; Frampton C; Gearry R; McNabb W; Roy N; Sarvestan JBackground: Functional dyspepsia is a common gastrointestinal condition that reduces the quality of life and increases health care costs. The lack of well-defined causes limits effective treatments. Consumers report using mānuka honey to treat gastrointestinal symptoms, although clinical evidence supporting such use is limited. Preclinical studies suggest its unique bioactive compounds may reduce gastrointestinal inflammation. Recently, 3,6,7-trimethyllumazine (Lepteridine), a natural pteridine in mānuka honey, was shown to inhibit enzymes involved in gastrointestinal inflammation in in vitro studies. Therefore, Lepteridine-standardized mānuka honey may deliver digestive health benefits. Objective: The aim of this feasibility study is to gather the data required to estimate sample size and support study logistics to design future trials. The primary objective will be preliminary assessments of the impact of Lepteridine-standardized mānuka honey on symptom severity and the quality of life in participants with mild-to-moderate functional dyspepsia. Other feasibility objectives include assessing the biological responses to mānuka honey standardized to medium and high levels of Lepteridine and measuring mānuka honey–derived metabolites in blood and urine. Methods: This is a 3-arm, parallel, controlled, double-blind, randomized feasibility study. A total of 75 healthy adults with symptoms of functional dyspepsia (Rome IV criteria) and mild-to-moderate dyspepsia severity (Short Form Leeds Dyspepsia Questionnaire) were recruited between October 2022 and September 2023. Participants were randomized into one of three groups: (1) mānuka honey standardized to contain 10 mg/kg Lepteridine, (2) mānuka honey standardized to contain 40 mg/kg Lepteridine, or (3) honey maple flavored syrup control. After a 2-week lead-in period, participants consumed 10 g of allocated intervention twice daily for 6 weeks. Throughout the study, participants completed daily bowel movement diaries and validated weekly questionnaires about their gastrointestinal symptoms and quality of life. Stool samples and 3-day diet records were collected at baseline and the end of the intervention. Blood samples were collected at baseline, weeks 2 and 4, and at the end of the intervention. In addition, 6 healthy participants without symptoms of functional dyspepsia were recruited to undergo an acute 5-hour assessment for the appearance of Lepteridine and related metabolites in plasma and urine following consumption of Lepteridine-standardized mānuka honey. The study was approved by the Northern B Health and Disability Ethics Committee. Results: Initial analysis includes 68 participants, with laboratory and data analyses being undertaken as of March 2024. The results of the primary and secondary outcomes will be published in peer-reviewed journals. Conclusions: This study will provide essential information on the potential efficacy and suitability of Lepteridine-standardized mānuka honey for designing future clinical trials investigating its effect in treating symptoms of functional dyspepsia. Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12622001140741p; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384094 International Registered Report Identifier (IRRID): DERR1-10.2196/66417Item Effects of defatted rice bran-fortified bread on gut microbiome, cardiovascular risk, gut discomfort, wellbeing and gut physiology in healthy adults with low dietary fibre intake(Elsevier Ltd on behalf of the European Society for Clinical Nutrition and Metabolism, 2025-06) Ng HM; Maggo J; Wall CL; Bayer SB; Mullaney JA; Cabrera D; Fraser K; Cooney JM; Günther CS; McNabb WC; Foster M; Frampton C; Gearry RB; Roy NCBackground & aims: Inadequate dietary fibre (DF) intake is associated with suboptimal gut function and increased risk of several human diseases. Bread is commonly consumed and is ideal to incorporate cereal bran to increase DF content. No human studies have investigated the effects of defatted rice bran (DRB) in bread, which has triple the DF of white bread, purported hypo-allergenicity and a unique nutrient profile, as a dietary intervention in healthy adults. This study aims to assess the relative abundances of a composite of key faecal microbial genera and species involved in DF fermentation and metabolism following the habitual intake of DRB-fortified bread and its influence on other biological markers of host and microbial interactions, cardiovascular risk profile, patient-reported outcomes, total DF intake, and gut physiology in healthy adults with low baseline DF intake. Methods: Fifty-six healthy adults with low baseline DF intake (<18 g/day (females), <22 g/day (males)) completed a two-arm, placebo-controlled, double-blind, randomised, crossover study. Participants consumed three (females) or four (males) slices of DRB-fortified bread or control bread daily as part of their usual diet for four weeks, with the intervention periods separated by a two-week washout. Outcomes included faecal microbiota composite (primary outcome); relative abundances (taxa and gene); faecal moisture content and bile acid concentrations; plasma and faecal organic acid concentrations; cardiovascular risk profile; gut comfort, psychological wellbeing parameters; total DF intake; whole gut transit time, and were measured at baseline and following each intervention phase. Additionally, in a sub-study, 15 participants ingested gas-sensing capsules to assess whole and regional gut transit times, and total and regional colonic hydrogen and carbon dioxide concentrations at the same timepoints. Results: DRB-fortified bread consumption significantly increased total DF intake from 20.7 g/day to 43.4 g/day (p < 0.001). No significant differences were observed in the primary outcome, microbial taxa composite within and between groups (False Discovery Rate (FDR) correction, p > 0.10). As compared to control, the DRB group had increased relative abundances of Faecalibacterium prausnitzii (unadjusted p = 0.04), Bifidobacterium longum (unadjusted p = 0.12), and Bacteroides ovatus (unadjusted p = 0.10); lower relative abundances in Coprococcus genus (unadjusted p = 0.09), Roseburia faecis (unadjusted p = 0.02) and Prevotella copri species (unadjusted p = 0.05). However, no significant differences were observed in the relative abundances of these taxa within and between groups (FDR correction p > 0.10) and for most of the other outcomes between groups (p > 0.05). Only mean serum high-density lipoprotein (HDL) concentrations significantly increased (p = 0.006), and mean total cholesterol (TC) to HDL concentration ratio significantly lowered (p = 0.02) in the DRB group compared to the control group. Conclusion: This is the first human study to show that a high-DF DRB-fortified bread improved DF intake, HDL cholesterol profiles, and may affect the gut microbiota composition in healthy adults with low DF intake. These findings support the substitution of white bread with DRB-fortified bread as an effective method to improve DF intake, which may have subsequent benefits on gut physiology and metabolic health.Item Study Protocol for a Randomized Controlled Trial Investigating the Effects of the Daily Consumption of Ruminant Milk on Digestive Comfort and Nutrition in Older Women: The YUMMI Study.(MDPI (Basel, Switzerland), 2024-12-06) Ong SP; Miller JC; McNabb WC; Gearry RB; Ware LM; Mullaney JA; Fraser K; Hort J; Bayer SB; Frampton CMA; Roy NC; Miranda JMBACKGROUND: Age-related changes can lead to dietary insufficiency in older adults. The inclusion of high-quality, nutrient-dense foods such as ruminant milks can significantly improve health outcomes. However, many older adults worldwide do not meet daily milk intake recommendations because of digestive discomfort and health concerns. Ovine and caprine milks are increasingly popular for their perceived digestive and nutritional benefits. While preclinical studies suggest differences in milk digestion, human studies investigating acute postprandial responses remain inconclusive, and the impacts of sustained milk consumption remain uncertain. OBJECTIVES: Hence, we present a randomized controlled trial investigating how the sustained consumption of bovine, caprine, or ovine milk influences digestion, nutrition, and metabolism in older women. METHODS: A total of 165 healthy older women were randomized to receive bovine, caprine, or ovine milk, or no milk, twice daily for 12 weeks. The primary outcome is the impact of milk consumption on digestive comfort assessed via the Gastrointestinal Syndrome Rating Scale (GSRS). Secondary outcomes include changes in nutrient intake, plasma amino acid and lipid appearance, bowel habits, the gut microbiota, cardiometabolic health, physical function, physical activity, sleep, mood, sensory perception, and emotional response. CONCLUSIONS: The findings could inform dietary recommendations for older women and facilitate the development of targeted functional food products.Item 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 HThere 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.Item 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 WCThis 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.Item The impact of ethnicity and intra-pancreatic fat on the postprandial metabolome response to whey protein in overweight Asian Chinese and European Caucasian women with prediabetes(Frontiers Media S.A., 2022-10-14) Joblin-Mills A; Wu Z; Fraser K; Jones B; Yip W; Lim JJ; Lu L; Sequeira I; Poppitt S; Li XThe “Thin on the Outside Fat on the Inside” TOFI_Asia study found Asian Chinese to be more susceptible to Type 2 Diabetes (T2D) compared to European Caucasians matched for gender and body mass index (BMI). This was influenced by degree of visceral adipose deposition and ectopic fat accumulation in key organs, including liver and pancreas, leading to altered fasting plasma glucose, insulin resistance, and differences in plasma lipid and metabolite profiles. It remains unclear how intra-pancreatic fat deposition (IPFD) impacts TOFI phenotype-related T2D risk factors associated with Asian Chinese. Cow’s milk whey protein isolate (WPI) is an insulin secretagogue which can suppress hyperglycemia in prediabetes. In this dietary intervention, we used untargeted metabolomics to characterize the postprandial WPI response in 24 overweight women with prediabetes. Participants were classified by ethnicity (Asian Chinese, n=12; European Caucasian, n=12) and IPFD (low IPFD < 4.66%, n=10; high IPFD ≥ 4.66%, n=10). Using a cross-over design participants were randomized to consume three WPI beverages on separate occasions; 0 g (water control), 12.5 g (low protein, LP) and 50 g (high protein, HP), consumed when fasted. An exclusion pipeline for isolating metabolites with temporal (T0-240mins) WPI responses was implemented, and a support vector machine-recursive feature elimination (SVM-RFE) algorithm was used to model relevant metabolites by ethnicity and IPFD classes. Metabolic network analysis identified glycine as a central hub in both ethnicity and IPFD WPI response networks. A depletion of glycine relative to WPI concentration was detected in Chinese and high IPFD participants independent of BMI. Urea cycle metabolites were highly represented among the ethnicity WPI metabolome model, implicating a dysregulation in ammonia and nitrogen metabolism among Chinese participants. Uric acid and purine synthesis pathways were enriched within the high IPFD cohort’s WPI metabolome response, implicating adipogenesis and insulin resistance pathways. In conclusion, the discrimination of ethnicity from WPI metabolome profiles was a stronger prediction model than IPFD in overweight women with prediabetes. Each models’ discriminatory metabolites enriched different metabolic pathways that help to further characterize prediabetes in Asian Chinese women and women with increased IPFD, independently.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 The impact of heat treatment of bovine milk on gastric emptying and nutrient appearance in peripheral circulation in healthy females: a randomized controlled trial comparing pasteurized and ultra-high temperature milk(Elsevier Inc on behalf of the American Society for Nutrition, 2024-05-01) Milan AM; Barnett MPG; McNabb WC; Roy NC; Coutinho S; Hoad CL; Marciani L; Nivins S; Sharif H; Calder S; Du P; Gharibans AA; O'Grady G; Fraser K; Bernstein D; Rosanowski SM; Sharma P; Shrestha A; Mithen RFBACKGROUND: Heat treatments of dairy, including pasteurization and ultra-high temperature (UHT) processing, alter milk macromolecular structures, and ultimately affect digestion. In vitro, animal, and human studies show faster nutrient release or circulating appearance after consuming UHT milk (UHT-M) compared with pasteurized milk (PAST-M), with a faster gastric emptying (GE) rate proposed as a possible mechanism. OBJECTIVES: To investigate the impact of milk heat treatment on GE as a mechanism of faster nutrient appearance in blood. We hypothesized that GE and circulating nutrient delivery following consumption would be faster for UHT-M than PAST-M. METHODS: In this double-blind randomized controlled cross-over trial, healthy female (n = 20; 27.3 ± 1.4 y, mean ± SD) habitual dairy consumers, consumed 500 mL of either homogenized bovine UHT-M or PAST-M (1340 compared with 1320 kJ). Gastric content volume (GCV) emptying half-time (T50) was assessed over 3 h by magnetic resonance imaging subjective digestive symptoms, plasma amino acid, lipid and B vitamin concentrations, and gastric myoelectrical activity were measured over 5 h. RESULTS: Although GCV T50 did not differ (102 ± 7 min compared with 89 ± 8 min, mean ± SEM, UHT-M and PAST-M, respectively; P = 0.051), GCV time to emptying 25% of the volume was 31% longer following UHT-M compared with PAST-M (42 ± 2 compared with 32 ± 4 min, P = 0.004). Although GCV remained larger for a longer duration following UHT-M (treatment × time interaction, P = 0.002), plasma essential amino acid AUC was greater following UHT-M than PAST-M (55,324 ± 3809 compared with 36,598 ± 5673 μmol·min·L-1, P = 0.006). Heat treatment did not impact gastric myoelectrical activity, plasma appetite hormone markers or subjective appetite scores. CONCLUSIONS: Contrary to expectations, GE was slower with UHT-M, yet, as anticipated, aminoacidemia was greater. The larger GCV following UHT-M suggests that gastric volume may poorly predict circulating nutrient appearance from complex food matrices. Dairy heat treatment may be an effective tool to modify nutrient release by impacting digestion kinetics. CLINICAL TRIAL REGISTRY: www.anzctr.org.au (ACTRN12620000172909).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.