Journal Articles

Permanent URI for this collectionhttps://mro.massey.ac.nz/handle/10179/7915

Browse

Filters

2013 - 201962020 - 202423

Settings

Author: search.filters.author.Young WHas files: Yes

Search Results

Now showing 1 - 10 of 29
  • Thumbnail Image
    Item
    Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice.
    (John Wiley and Sons Inc., 2019-01-01) Poyntz HC; Jones A; Jauregui R; Young W; Gestin A; Mooney A; Lamiable O; Altermann E; Schmidt A; Gasser O; Weyrich L; Jolly CJ; Linterman MA; Gros GL; Hawkins ED; Forbes-Blom E
    Antibody-mediated immunity is highly protective against disease. The majority of current vaccines confer protection through humoral immunity, but there is high variability in responsiveness across populations. Identifying immune mechanisms that mediate low antibody responsiveness may provide potential strategies to boost vaccine efficacy. Here, we report diverse antibody responsiveness to unadjuvanted as well as adjuvanted immunization in substrains of BALB/c mice, resulting in high and low antibody response phenotypes. Furthermore, these antibody phenotypes were not affected by changes in environmental factors such as the gut microbiota composition. Antigen-specific B cells following immunization had a marked difference in capability to class switch, resulting in perturbed IgG isotype antibody production. In vitro, a B-cell intrinsic defect in the regulation of class-switch recombination was identified in mice with low IgG antibody production. Whole genome sequencing identified polymorphisms associated with the magnitude of antibody produced, and we propose candidate genes that may regulate isotype class-switching capability. This study highlights that mice sourced from different vendors can have significantly altered humoral immune response profiles, and provides a resource to interrogate genetic regulators of antibody responsiveness. Together these results further our understanding of immune heterogeneity and suggest additional research on the genetic influences of adjuvanted vaccine strategies is warranted for enhancing vaccine efficacy.
  • Thumbnail Image
    Item
    Peripherally Restricted Activation of Opioid Receptors Influences Anxiety-Related Behaviour and Alters Brain Gene Expression in a Sex-Specific Manner.
    (MDPI (Basel, Switzerland), 2024-12-07) Parkar N; Young W; Olson T; Hurst C; Janssen P; Spencer NJ; McNabb WC; Dalziel JE; Szumlinski KK; Shiina T
    Although effects of stress-induced anxiety on the gastrointestinal tract and enteric nervous system (ENS) are well studied, how ENS dysfunction impacts behaviour is not well understood. We investigated whether ENS modulation alters anxiety-related behaviour in rats. We used loperamide, a potent μ-opioid receptor agonist that does not cross the blood-brain barrier, to manipulate ENS function and assess changes in behaviour, gut and brain gene expression, and microbiota profile. Sprague Dawley (male/female) rats were acutely dosed with loperamide (subcutaneous) or control solution, and their behavioural phenotype was examined using open field and elevated plus maze tests. Gene expression in the proximal colon, prefrontal cortex, hippocampus, and amygdala was assessed by RNA-seq and caecal microbiota composition determined by shotgun metagenome sequencing. In female rats, loperamide treatment decreased distance moved and frequency of supported rearing, indicating decreased exploratory behaviour and increased anxiety, which was associated with altered hippocampal gene expression. Loperamide altered proximal colon gene expression and microbiome composition in both male and female rats. Our results demonstrate the importance of the ENS for communication between gut and brain for normo-anxious states in female rats and implicate corticotropin-releasing hormone and gamma-aminobutyric acid gene signalling pathways in the hippocampus. This study also sheds light on sexually dimorphic communication between the gut and the brain. Microbiome and colonic gene expression changes likely reflect localised effects of loperamide related to gut dysmotility. These results suggest possible ENS pharmacological targets to alter gut to brain signalling for modulating mood.
  • Thumbnail Image
    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 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.
  • Thumbnail Image
    Item
    Novel insights into mechanisms of inhibition of colonic motility by loperamide
    (Frontiers Media S.A., 2024-08-29) Parkar N; Spencer NJ; Wiklendt L; Olson T; Young W; Janssen P; McNabb WC; Dalziel JE; Abalo, R
    BACKGROUND: It is well known that opiates slow gastrointestinal (GI) transit, via suppression of enteric cholinergic neurotransmission throughout the GI tract, particularly the large intestine where constipation is commonly induced. It is not clear whether there is uniform suppression of enteric neurotransmission and colonic motility across the full length of the colon. Here, we investigated whether regional changes in colonic motility occur using the peripherally-restricted mu opioid agonist, loperamide to inhibit colonic motor complexes (CMCs) in isolated mouse colon. METHODS: High-resolution video imaging was performed to monitor colonic wall diameter on isolated whole mouse colon. Regional changes in the effects of loperamide on the pattern generator underlying cyclical CMCs and their propagation across the full length of large intestine were determined. RESULTS: The sensitivity of CMCs to loperamide across the length of colon varied significantly. Although there was a dose-dependent inhibition of CMCs with increasing concentrations of loperamide (10 nM - 1 μM), a major observation was that in the mid and distal colon, CMCs were abolished at low doses of loperamide (100 nM), while in the proximal colon, CMCs persisted at the same low concentration, albeit at a significantly slower frequency. Propagation velocity of CMCs was significantly reduced by 46%. The inhibitory effects of loperamide on CMCs were reversed by naloxone (1 μM). Naloxone alone did not change ongoing CMC characteristics. DISCUSSION: The results show pronounced differences in the inhibitory action of loperamide across the length of large intestine. The most potent effect of loperamide to retard colonic transit occurred between the proximal colon and mid/distal regions of colon. One of the possibilities as to why this occurs is because the greatest density of mu opioid receptors are located on interneurons responsible for neuro-neuronal transmission underlying CMCs propagation between the proximal and mid/distal colon. The absence of effect of naloxone alone on CMC characteristics suggest that the mu opioid receptor has little ongoing constitutive activity under our recording conditions.
  • Thumbnail Image
    Item
    In vitro Fermentation of Digested Milk Fat Globule Membrane From Ruminant Milk Modulates Piglet Ileal and Caecal Microbiota
    (Frontiers Media S.A., 2020-07-09) Thum C; Young W; Montoya CA; Roy NC; McNabb WC; Benítez-Páez A
    Lipids in milk are secreted as a triacylglycerol core surrounded by a trilayer membrane, the milk fat globule membrane (MFGM). This membrane, known to have important roles in infant brain and intestinal development, is composed of proteins, glycoproteins, and complex lipids. We hypothesized that some of the beneficial properties of MFGM are due to its effects on the gastrointestinal microbiota. This study aimed to determine the effect of a commercial phospholipid concentrate (PC) and enriched bovine, caprine, and ovine MFGM fractions on ileal and hindgut microbiota in vitro. Digestion of PC and MFGMs was conducted using an in vitro model based on infant gastric and small intestine conditions. The recovered material was then in vitro fermented with ileal and caecal inocula prepared from five piglets fed a commercial formula for 20 days before ileal and caecal digesta were collected. After each fermentation, samples were collected to determine organic acid production and microbiota composition using 16S rRNA sequencing. All substrates, except PC (5%), were primarily fermented by the ileal microbiota (8-14%) (P < 0.05). PC and caprine MFGM reduced ileal microbiota alpha diversity compared to ileal inoculum. Caprine MFGM increased and PC reduced the ileal ratio of firmicutes:proteobacteria (P < 0.05), respectively, compared to the ileal inoculum. Bovine and ovine MFGMs increased ileal production of acetic, butyric, and caproic acids compared to other substrates and reduced the proportions of ileal proteobacteria (P < 0.0001). There was a limited fermentation of bovine (3%), caprine (2%), and ovine (2%) MFGMs by the caecal microbiota compared to PC (14%). In general, PC and all MFGMs had a reduced effect on caecal microbiota at a phylum level although MFG source-specific effects were observed at the genus level. These indicate that the main effects of the MFGM in the intestinal microbial population appears to occur in the ileum.
  • Thumbnail Image
    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 C
    Amino 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.
  • Thumbnail Image
    Item
    Gut-Brain Axis in the Early Postnatal Years of Life: A Developmental Perspective
    (Frontiers Media S.A., 2020-08-05) Jena A; Montoya CA; Mullaney JA; Dilger RN; Young W; McNabb WC; Roy NC; Cammarota M
    Emerging evidence suggests that alterations in the development of the gastrointestinal (GI) tract during the early postnatal period can influence brain development and vice-versa. It is increasingly recognized that communication between the GI tract and brain is mainly driven by neural, endocrine, immune, and metabolic mediators, collectively called the gut-brain axis (GBA). Changes in the GBA mediators occur in response to the developmental changes in the body during this period. This review provides an overview of major developmental events in the GI tract and brain in the early postnatal period and their parallel developmental trajectories under physiological conditions. Current knowledge of GBA mediators in context to brain function and behavioral outcomes and their synthesis and metabolism (site, timing, etc.) is discussed. This review also presents hypotheses on the role of the GBA mediators in response to the parallel development of the GI tract and brain in infants.
  • Thumbnail Image
    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 A
    Bile 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.
  • Thumbnail Image
    Item
    Slowed gastrointestinal transit is associated with an altered caecal microbiota in an aged rat model
    (Frontiers Media S.A., 2023-03-14) Parkar N; Dalziel JE; Spencer NJ; Janssen P; McNabb WC; Young W; Butcher J
    Gastrointestinal (GI) motility is largely dependent upon activity within the enteric nervous system (ENS) and is an important part of the digestive process. Dysfunction of the ENS can impair GI motility as is seen in the case of constipation where gut transit time is prolonged. Animal models mimicking symptoms of constipation have been developed by way of pharmacological manipulations. Studies have reported an association between altered GI motility and gut microbial population. Little is known about the changes in gut microbiota profile resulting specifically from pharmacologically induced slowed GI motility in rats. Moreover, the relationship between gut microbiota and altered intestinal motility is based on studies using faecal samples, which are easier to obtain but do not accurately reflect the intestinal microbiome. The aim of this study was to examine how delayed GI transit due to opioid receptor agonism in the ENS modifies caecal microbiota composition. Differences in caecal microbial composition of loperamide-treated or control male Sprague Dawley rats were determined by 16S rRNA gene amplicon sequencing. The results revealed that significant differences were observed at both genus and family level between treatment groups. Bacteroides were relatively abundant in the loperamide-induced slowed GI transit group, compared to controls. Richness and diversity of the bacterial communities was significantly lower in the loperamide-treated group compared to the control group. Understanding the link between specific microbial species and varying transit times is crucial to design interventions targeting the microbiome and to treat intestinal motility disorders.
  • Thumbnail Image
    Item
    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.