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Author: search.filters.author.Young WSubject: search.filters.subject.Gastrointestinal Microbiome

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    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.
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    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.
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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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    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 G
    The 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.
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    Infant Complementary Feeding of Prebiotics for the Microbiome and Immunity
    (MDPI (Basel, Switzerland), 2019-02-09) McKeen S; Young W; Mullaney J; Fraser K; McNabb WC; Roy NC
    Complementary feeding transitions infants from a milk-based diet to solid foods, providing essential nutrients to the infant and the developing gut microbiome while influencing immune development. Some of the earliest microbial colonisers readily ferment select oligosaccharides, influencing the ongoing establishment of the microbiome. Non-digestible oligosaccharides in prebiotic-supplemented formula and human milk oligosaccharides promote commensal immune-modulating bacteria such as Bifidobacterium, which decrease in abundance during weaning. Incorporating complex, bifidogenic, non-digestible carbohydrates during the transition to solid foods may present an opportunity to feed commensal bacteria and promote balanced concentrations of beneficial short chain fatty acid concentrations and vitamins that support gut barrier maturation and immunity throughout the complementary feeding window.
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    Metabolome and microbiome profiling of a stress-sensitive rat model of gut-brain axis dysfunction
    (Springer Nature Limited, 2019-10-01) Bassett SA; Young W; Fraser K; Dalziel JE; Webster J; Ryan L; Fitzgerald P; Stanton C; Dinan TG; Cryan JF; Clarke G; Hyland N; Roy NC
    Stress negatively impacts gut and brain health. Individual differences in response to stress have been linked to genetic and environmental factors and more recently, a role for the gut microbiota in the regulation of stress-related changes has been demonstrated. However, the mechanisms by which these factors influence each other are poorly understood, and there are currently no established robust biomarkers of stress susceptibility. To determine the metabolic and microbial signatures underpinning physiological stress responses, we compared stress-sensitive Wistar Kyoto (WKY) rats to the normo-anxious Sprague Dawley (SD) strain. Here we report that acute stress-induced strain-specific changes in brain lipid metabolites were a prominent feature in WKY rats. The relative abundance of Lactococcus correlated with the relative proportions of many brain lipids. In contrast, plasma lipids were significantly elevated in response to stress in SD rats, but not in WKY rats. Supporting these findings, we found that the greatest difference between the SD and WKY microbiomes were the predicted relative abundance of microbial genes involved in lipid and energy metabolism. Our results provide potential insights for developing novel biomarkers of stress vulnerability, some of which appear genotype specific.
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    Gut Microbial Metabolites and Biochemical Pathways Involved in Irritable Bowel Syndrome: Effects of Diet and Nutrition on the Microbiome
    (Elsevier Inc on behalf of the American Society for Nutrition, 2020-05) James SC; Fraser K; Young W; McNabb WC; Roy NC
    The food we consume and its interactions with the host and their gut microbiota affect normal gut function and health. Functional gut disorders (FGDs), including irritable bowel syndrome (IBS), can result from negative effects of these interactions, leading to a reduced quality of life. Certain foods exacerbate or reduce the severity and prevalence of FGD symptoms. IBS can be used as a model of perturbation from normal gut function with which to study the impact of foods and diets on the severity and symptoms of FGDs and understand how critical processes and biochemical mechanisms contribute to this impact. Analyzing the complex interactions between food, host, and microbial metabolites gives insights into the pathways and processes occurring in the gut which contribute to FGDs. The following review is a critical discussion of the literature regarding metabolic pathways and dietary interventions relevant to FGDs. Many metabolites, for example bile acids, SCFAs, vitamins, amino acids, and neurotransmitters, can be altered by dietary intake, and could be valuable for identifying perturbations in metabolic pathways that distinguish a "normal, healthy" gut from a "dysfunctional, unhealthy" gut. Dietary interventions for reducing symptoms of FGDs are becoming more prevalent, but studies investigating the underlying mechanisms linked to host, microbiome, and metabolite interactions are less common. Therefore, we aim to evaluate the recent literature to assist with further progression of research in this field.
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    In Vitro Fermentation of Sheep and Cow Milk Using Infant Fecal Bacteria
    (MDPI (Basel, Switzerland), 2020-06-17) Ahlborn N; Young W; Mullaney J; Samuelsson LM
    While human milk is the optimal food for infants, formulas that contain ruminant milk can have an important role where breastfeeding is not possible. In this regard, cow milk is most commonly used. However, recent years have brought interest in other ruminant milk. While many similarities exist between ruminant milk, there are likely enough compositional differences to promote different effects in the infant. This may include effects on different bacteria in the large bowel, leading to different metabolites in the gut. In this study sheep and cow milk were digested using an in vitro infant digestive model, followed by fecal fermentation using cultures inoculated with fecal material from two infants of one month and five months of age. The effects of the cow and sheep milk on the fecal microbiota, short-chain fatty acids (SCFA), and other metabolites were investigated. Significant differences in microbial, SCFA, and metabolite composition were observed between fermentation of sheep and cow milk using fecal inoculum from a one-month-old infant, but comparatively minimal differences using fecal inoculum from a five-month-old infant. These results show that sheep milk and cow milk can have differential effects on the gut microbiota, while demonstrating the individuality of the gut microbiome.
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    Smart capsules for sensing and sampling the gut: status, challenges and prospects
    (BMJ Publishing Group Ltd on behalf of the British Society of Gastroenterology, 2024-01) Rehan M; Al-Bahadly I; Thomas DG; Young W; Cheng LK; Avci E
    Smart capsules are developing at a tremendous pace with a promise to become effective clinical tools for the diagnosis and monitoring of gut health. This field emerged in the early 2000s with a successful translation of an endoscopic capsule from laboratory prototype to a commercially viable clinical device. Recently, this field has accelerated and expanded into various domains beyond imaging, including the measurement of gut physiological parameters such as temperature, pH, pressure and gas sensing, and the development of sampling devices for better insight into gut health. In this review, the status of smart capsules for sensing gut parameters is presented to provide a broad picture of these state-of-the-art devices while focusing on the technical and clinical challenges the devices need to overcome to realise their value in clinical settings. Smart capsules are developed to perform sensing operations throughout the length of the gut to better understand the body's response under various conditions. Furthermore, the prospects of such sensing devices are discussed that might help readers, especially health practitioners, to adapt to this inevitable transformation in healthcare. As a compliment to gut sensing smart capsules, significant amount of effort has been put into the development of robotic capsules to collect tissue biopsy and gut microbiota samples to perform in-depth analysis after capsule retrieval which will be a game changer for gut health diagnosis, and this advancement is also covered in this review. The expansion of smart capsules to robotic capsules for gut microbiota collection has opened new avenues for research with a great promise to revolutionise human health diagnosis, monitoring and intervention.
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    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 S
    Background: 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:e56772