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    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.
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    Modulation of enteric neural activity and its influence on brain function and behaviour : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Manawatu, New Zealand
    (Massey University, 2024) Parkar, Nabil Jamil
    The gut-brain axis (GBA) facilitates bidirectional communication between the enteric nervous system (ENS) of the gastrointestinal (GI) tract and the central nervous system (CNS). The location of the ENS along the GI tract enables it to serve as a relay station along the GBA. A key regulator of the GBA is the diverse population of microbial communities inhabiting the GI tract, known as the gut microbiota. Due to its proximity to the ENS, gut microbes significantly influence ENS functions, such as gut motility, and also impact brain function and behavior. A diverse and healthy gut microbiota is crucial for normal GI physiology and mental health. Understanding the physiological host factors that influence and control the gut microbiota is essential for grasping its variability in health and states of dysbiosis. Movement of luminal content along the GI tract, primarily driven by rhythmic contractions of GI smooth muscles, affects gut microbiota growth and population dynamics. This research involved a series of ex vivo and behavioral experiments in rodents to better understand ENS control of gut motility and its impact on anxiety-related behavior. Initially, the effect of a specific pharmacological agent on colonic motility patterns was evaluated using ex vivo techniques. Observations from this study provided fundamental insights into ENS function and its regulation of colonic motility, laying the foundation for further research on how altered colonic motility via ENS manipulation affects gut microbiota composition and anxiety-related behavior. The second study investigated whether pharmacological modulation of the ENS, resulting in reduced colonic motility, affected the gut microbiota. Results revealed significant changes in gut microbiota composition, including decreased abundance of certain bacterial species and alterations in community structure. The final study aimed to understand the relationship between ENS manipulation, brain function, and behavior by inducing changes in gut motility. Anxiety-related behavior was assessed in rats using open field and elevated plus maze tests, focusing on those exposed to a pharmacological agent that slowed colonic motility via specific ENS receptors. To determine if behavior changes involved specific neural pathways, brain gene expression in key regions was studied. Additionally, the potential relationship between gut microbiota and brain function was explored, assessing if ENS modulation and behavioral effects correlated with changes in gene expression and microbiota profiles in the large intestine. Findings indicated that ENS modulation altered anxiety-related behavior in a sex-specific manner, with female rats showing increased anxiety and corresponding changes in brain and proximal colon gene expression compared to males. This study highlighted sexually dimorphic gut-brain communication and suggested multiple genes/pathways may influence anxiety-related behavior in females. This comprehensive exploration through three interrelated studies has provided new insights into the regional specificity of ENS receptors in regulating colonic motility, the impact of slowed gut transit on microbiota composition, and the physiological consequences of ENS modulation on brain function and anxiety, with associated sex differences. A combined analysis of these findings discusses their implications for understanding the ENS as a key player in regulating the gut-brain axis.
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    The effects of ruminant milk treatments on hippocampal, striatal, and prefrontal cortex gene expression in pigs as a model for the human infant
    (Frontiers Media S.A., 2022-08-15) Jena A; Montoya CA; Young W; Mullaney JA; Roy D; Dilger RN; Giezenaar C; McNabb WC; Roy NC; Lim CK
    While infant formula is usually bovine milk-based, interest in other ruminant milk-based formulas is growing. However, whether different ruminant milk treatments with varying nutrient compositions influence the infant's brain development remains unknown. The aim was to determine the effects of consuming bovine, caprine, or ovine milk on brain gene expression in the early postnatal period using a pig model of the human infant. Starting at postnatal day 7 or 8, pigs were exclusively fed bovine, ovine, or caprine milk for 15 days. The mRNA abundance of 77 genes in the prefrontal cortex, hippocampus, and striatum regions was measured at postnatal day 21 or 22 using NanoString. The expression level of two hippocampal and nine striatal genes was most affected by milk treatments, particularly ovine milk. These modulatory genes are involved in glutamate, gamma-aminobutyric acid, serotonin, adrenaline and neurotrophin signaling and the synaptic vesicle cycle. The expression level of genes involved in gamma-aminobutyric acid signaling was associated with pigs' lactose intake. In contrast, milk treatments did not affect the mRNA abundance of the genes in the prefrontal cortex. This study provides the first evidence of the association of different ruminant milk treatments with brain gene expression related to cognitive function in the first 3 months of postnatal life.