Journal Articles
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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 Differences in Compositions of Gut Bacterial Populations and Bacteriophages in 5-11 Year-Olds Born Preterm Compared to Full Term(Frontiers Media S.A., 2020-06-16) Jayasinghe TN; Vatanen T; Chiavaroli V; Jayan S; McKenzie EJ; Adriaenssens E; Derraik JGB; Ekblad C; Schierding W; Battin MR; Thorstensen EB; Cameron-Smith D; Forbes-Blom E; Hofman PL; Roy NC; Tannock GW; Vickers MH; Cutfield WS; O'Sullivan JM; Shkoporov APreterm infants are exposed to major perinatal, post-natal, and early infancy events that could impact on the gut microbiome. These events include infection, steroid and antibiotic exposure, parenteral nutrition, necrotizing enterocolitis, and stress. Studies have shown that there are differences in the gut microbiome during the early months of life in preterm infants. We hypothesized that differences in the gut microbial composition and metabolites in children born very preterm persist into mid-childhood. Participants were healthy prepubertal children aged 5-11 years who were born very preterm (≤32 weeks of gestation; n = 51) or at term (37-41 weeks; n = 50). We recorded the gestational age, birth weight, mode of feeding, mode of birth, age, sex, and the current height and weight of our cohort. We performed a multi'omics [i.e., 16S rRNA amplicon and shotgun metagenomic sequencing, SPME-GCMS (solid-phase microextraction followed by gas chromatography-mass spectrometry)] analysis to investigate the structure and function of the fecal microbiome (as a proxy of the gut microbiota) in our cross-sectional cohort. Children born very preterm were younger (7.8 vs. 8.3 years; p = 0.034), shorter [height-standard deviation score (SDS) 0.31 vs. 0.92; p = 0.0006) and leaner [BMI (body mass index) SDS -0.20 vs. 0.29; p < 0.0001] than the term group. Children born very preterm had higher fecal calprotectin levels, decreased fecal phage richness, lower plasma arginine, lower fecal branched-chain amino acids and higher fecal volatile (i.e., 3-methyl-butanoic acid, butyrolactone, butanoic acid and pentanoic acid) profiles. The bacterial microbiomes did not differ between preterm and term groups. We speculate that the observed very preterm-specific changes were established in early infancy and may impact on the capacity of the very preterm children to respond to environmental changes.Item Variation in milk fat globule size and composition: A source of bioactives for human health(Taylor and Francis Group, 2023) Thum C; Roy NC; Everett DW; McNabb WCMilk fat globules (MFGs) are secreted from the mammalian gland and are composed of a triacylglycerol core surrounded by a triple membrane structure, the milk fat globule membrane (MFGM). The MFGM contains complex lipids and proteins reported to have nutritional, immunological, neurological and digestive functions. Human and ruminant milk are shown to share a similar MFG structure but with different size, profile and abundance of protein and polar lipids. This review summarizes the reported data on human, bovine, caprine and ovine MFG composition and concentration of bioactive components in different MFG-size fractions. A comprehensive understanding of compositional variations between milk from different species and MFG size fractions may help promote various milk sources as targeted supplements to improve human development and health. MFG size and MFGM composition are species-specific and affected by lactation, diet and breed (or maternal origin). Purification and enrichment methods for some bioactive proteins and lipids present in the MFGM have yet to be established or are not scaled sufficiently to be used to supplement human diets. To overcome this problem, MFG size selection through fractionation or herd selection may provide a convenient way to pre-enrich the MFG fraction with specific protein and lipid components to fulfill human dietary and health requirements.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 The impact of heat-set milk protein gel textures modified by pH on circulating amino acid appearance and gastric function in healthy female adults: a randomised controlled trial.(Royal Society of Chemistry, 2024-05-21) Milan AM; Menting GGA; Barnett MPG; Liu Y; McNabb WC; Roy NC; Hutchings SC; Mungure T; Weeks M; Li S; Hort J; Calder S; O'Grady G; Mithen RFModification of dairy proteins during processing impacts structural assemblies, influencing textural and nutritional properties of dairy products, and release and availability of amino acids during digestion. By modifying only pH, acid heat-set bovine dairy gels with divergent textural properties were developed to alter protein digestion. In vitro assay confirmed faster digestion of protein from a firm gel (pH 5.65) versus a soft gel (pH 6.55). We hypothesised that firm gel (FIRM-G; pH 5.6) would result in greater indispensable amino acid (IAA) appearance in circulation over 5 h and corresponding differences in gastric myoelectrical activity relative to soft gel (SOFT-G; pH 6.2). In a randomised, single-blind cross-over trial, healthy females (n = 20) consumed 150 g of each gel; plasma amino acid appearance was assessed over 5 hours. Iso-nitrogenous, iso-caloric gels were prepared from identical mixtures of bovine milk and whey protein concentrates; providing 17.7 g (FIRM-G) and 18.9 g (SOFT-G) of protein per serving. Secondary outcomes included gastric myoelectrical activity measured by body surface gastric mapping, glycaemic, triglyceridaemic, and subjective appetite and digestive responses. Overall plasma IAA (area under the curve) did not differ between gels. However, plasma IAA concentrations were higher, and increased more rapidly over time after SOFT-G compared with FIRM-G (1455 ± 53 versus 1350 ± 62 μmol L-1 at 30 min, p = 0.024). Similarly, total, branched-chain and dispensable amino acids were higher at 30 min with SOFT-G than FIRM-G (total: 3939 ± 97 versus 3702 ± 127 μmol L-1, p = 0.014; branched-chain: 677 ± 30 versus 619 ± 34 μmol L-1, p = 0.047; dispensable: 2334 ± 53 versus 2210 ± 76 μmol L-1, p = 0.032). All other measured parameters were similar between gels. Peak postprandial aminoacidaemia was higher and faster following ingestion of SOFT-G. Customised plasma amino acid appearance from dairy is achievable by altering gel coagulum structure using pH during processing and may have minimal influence on related postprandial responses, with implications for targeting food design for optimal health. The Clinical Trial Registry number is ACTRN12622001418763 (https://www.anzctr.org.au) registered November 7, 2022.Item 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 NCBACKGROUND: 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.Item Nourishing the Infant Gut Microbiome to Support Immune Health: Protocol of SUN (Seeding Through Feeding) Randomized Controlled Trial.(JMIR Publications, 2024-09-02) Wall CR; Roy NC; Mullaney JA; McNabb WC; Gasser O; Fraser K; Altermann E; Young W; Cooney J; Lawrence R; Jiang Y; Galland BC; Fu X; Tonkie JN; Mahawar N; Lovell AL; Ma SBackground: The introduction of complementary foods during the first year of life influences the diversity of the gut microbiome. How this diversity affects immune development and health is unclear. Objective: This study evaluates the effect of consuming kūmara or kūmara with added banana powder (resistant starch) compared to a reference control at 4 months post randomization on the prevalence of respiratory tract infections and the development of the gut microbiome. Methods: This study is a double-blind, randomized controlled trial of mothers and their 6-month-old infants (up to n=300) who have not yet started solids. Infants are randomized into one of 3 groups: control arm (C), standard kūmara intervention (K), and a kūmara intervention with added banana powder product (K+) to be consumed daily for 4 months until the infant is approximately 10 months old. Infants are matched for sex using stratified randomization. Data are collected at baseline (prior to commencing solid food) and at 2 and 4 months after commencing solid food (at around 8 and 10 months of age). Data and samples collected at each timepoint include weight and length, intervention adherence (months 2 and 4), illness and medication history, dietary intake (months 2 and 4), sleep (diary and actigraphy), maternal dietary intake, breast milk, feces (baseline and 4 months), and blood samples (baseline and 4 months). Results: The trial was approved by the Health and Disability Ethics Committee of the Ministry of Health, New Zealand (reference 20/NTA/9). Recruitment and data collection did not commence until January 2022 due to the COVID-19 pandemic. Data collection and analyses are expected to conclude in January 2024 and early 2025, respectively. Results are to be published in 2024 and 2025. Conclusions: The results of this study will help us understand how the introduction of a specific prebiotic complementary food affects the microbiota and relative abundances of the microbial species, the modulation of immune development, and infant health. It will contribute to the expanding body of research that aims to deepen our understanding of the connections between nutrition, gut microbiota, and early-life postnatal health. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12620000026921; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378654 International Registered Report Identifier (IRRID): DERR1-10.2196/56772 JMIR Res Protoc 2024;13:e56772Item Plasma metabolomic response to high-carbohydrate meals of differing glycaemic load in overweight women.(Springer Nature, 2023-04-21) Durainayagam B; Mitchell CJ; Milan AM; Kruger MC; Roy NC; Fraser K; Cameron-Smith DBACKGROUND: Metabolomic dysregulation following a meal in overweight individuals with the Metabolic Syndrome (MetS) involves multiple pathways of nutrient storage and oxidation. OBJECTIVE: The aim of the current study was to perform an acute cross-over intervention to examine the interactive actions of meal glycaemic load (GL) on the dynamic responses of the plasma metabolome in overweight females. METHODS: Postmenopausal women [63 ± 1.23y; Healthy (n = 20) and MetS (n = 20)] ingested two differing high-carbohydrate test meals (73 g carbohydrate; 51% energy) composed of either low glycemic index (LGI) or high (HGI) foods in a randomised sequence. Plasma metabolome was analysed using liquid chromatography-mass spectrometry (LC-MS). RESULTS: In the overweight women with MetS, there were suppressed postprandial responses for several amino acids (AAs), including phenylalanine, leucine, valine, and tryptophan, p < 0.05), irrespective of the meal type. Meal GL exerted a limited impact on the overall metabolomic response, although the postprandial levels of alanine were higher with the low GL meal and uric acid was greater following the high GL meal (p < 0.05). CONCLUSIONS: MetS participants exhibited reduced differences in the concentrations of a small set of AAs and a limited group of metabolites implicated in energy metabolism following the meals. However, the manipulation of meal GL had minimal impact on the postprandial metabolome. This study suggests that the GL of a meal is not a major determinant of postprandial response, with a greater impact exerted by the metabolic health of the individual. Trial registration Australia New Zealand Clinical Trials Registry: ACTRN12615001108505 (21/10/2015).Item Vitamin B and One-Carbon Metabolite Profiles Show Divergent Associations with Cardiometabolic Risk Markers but not Cognitive Function in Older New Zealand Adults: A Secondary Analysis of the REACH Study.(Elsevier B.V., 2023-12-07) Gillies NA; Milan AM; Cameron-Smith D; Mumme KD; Conlon CA; von Hurst PR; Haskell-Ramsay CF; Jones B; Roy NC; Coad J; Wall CR; Beck KLBACKGROUND: Vitamin B inadequacies and elevated homocysteine status have been associated with impaired cognitive and cardiometabolic health with aging. There is, however, a scarcity of research investigating integrated profiles of one-carbon (1C) metabolites in this context, including metabolites of interconnected folate, methionine, choline oxidation, and transsulfuration pathways. OBJECTIVES: The study aimed to examine associations between vitamins B and 1C metabolites with cardiometabolic health and cognitive function in healthy older adults, including the interactive effects of Apolipoprotein E-ε4 status. METHODS: Three hundred and thirteen healthy participants (65-74 y, 65% female) were analyzed. Vitamins B were estimated according to dietary intake (4-d food records) and biochemical status (serum folate and vitamin B12). Fasting plasma 1C metabolites were quantified by liquid chromatography with tandem mass spectrometry. Measures of cardiometabolic health included biochemical (lipid panel, blood glucose) and anthropometric markers. Cognitive function was assessed by the Computerized Mental Performance Assessment System (COMPASS) and Montreal Cognitive Assessment (MoCA). Associations were analyzed using multivariate linear (COMPASS, cardiometabolic health) and Poisson (MoCA) regression modeling. RESULTS: Over 90% of participants met dietary recommendations for riboflavin and vitamins B6 and B12, but only 78% of males and 67% of females achieved adequate folate intakes. Higher serum folate and plasma betaine and glycine concentrations were associated with favorable cardiometabolic markers, whereas higher plasma choline and homocysteine concentrations were associated with greater cardiometabolic risk based on body mass index and serum lipids concentration values (P< 0.05). Vitamins B and homocysteine were not associated with cognitive performance in this cohort, though higher glycine concentrations were associated with better global cognitive performance (P = 0.017), episodic memory (P = 0.016), and spatial memory (P = 0.027) scores. Apolipoprotein E-ε4 status did not modify the relationship between vitamins B or 1C metabolites with cognitive function in linear regression analyses. CONCLUSIONS: Vitamin B and 1C metabolite profiles showed divergent associations with cardiometabolic risk markers and limited associations with cognitive performance in this cohort of healthy older adults.