- Title
- Maternal probiotic intervention as a prophylaxis against the impact of neonatal stress: implications for irritable bowel syndrome
- Creator
- Barouei, Javad
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2013
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Neonatal stress is a common early life event, reported in some instances to be associated with adverse physiological alterations that persist into adulthood. This concept has been applied to the ontogeny of functional gastrointestinal disorders such as irritable bowel syndrome (IBS). The use of probiotics in IBS patients has emerged as a treatment approach to improve some IBS symptoms. In addition, new research in rodent models indicates that neonatal probiotic intervention may assist in the prevention of brain-gut axis dysfunctions believed to be associated with IBS. The aim of this study was to determine whether perinatal (both pre and post natal) maternal probiotic supplementation could act prophylactically to block endocrine, immune and gut dysfunctions in rats exposed to neonatal stress (maternal separation) either alone or in combination with adult exposure to stress. This model has been proposed to mimic most of the cardinal features of IBS. The first series of studies (Chapter 3) examined the effect of maternal probiotic intervention on HPA-axis responses and gut-associated neuroendocrine function including analysis of mRNA expression of corticotropin releasing hormone receptors 1 and 2 (CRH-R1 and CRH-R2), and nerve growth factor (NGF). The results of the study revealed that maternal probiotic intervention induced activation of neonatal stress pathways as indicated by greatly enhanced corticosterone levels, which persisted into adulthood, and exacerbated ACTH responses to stress in adulthood. Maternal probiotic intervention affected gut-associated neuroendocrine gene expression profiles depending on age, gender and stress protocol. These effects include synergism, antagonism and normalisation. The second series of studies (Chapter 4) examined the effect of maternal probiotic intervention on systemic and gut-associated immune functions. In this chapter plasma levels of cytokines IFN-γ, TNF-α and IL-6, plasma Haptoglobin and IgA, and luminal IgA levels were examined. While the stress protocol did not affect levels of the circulating cytokines in the offspring, maternal probiotic intervention down-regulated IFN-γ production (irrespective of stress conditions) and up-regulated IL-6 responses to neonatal or adult stress. Importantly however, maternal probiotic intervention enhanced immune defence capacity as indicated by increased plasma and luminal IgA. Maternal probiotic intervention was also associated with significant reductions in plasma haptoglobin levels in all stressed and non-stressed animals to well below the baseline levels indicating enhanced loss of hemoglobin. The third series of studies (Chapter 5) examined whether maternal probiotic intervention protected against gut microbiota and secretory state alterations induced by neonatal and/or adult stress. Neonatal and/or adult stress disrupted the normal balance of gut microbiota. Maternal probiotic intervention caused shifts in neonatal gut microflora as indicated by fostering an overgrowth of potential negative bacteria such as E. coli, enterococci and clostridia in stressed and non-stressed pups, resembling that of neonatally stressed pups in the vehicle subset. In adulthood maternal probiotic intervention was associated with a disruption of the normal balance of gut flora when coupled with neonatal stress, but also restoration of some gut bacterial groups to normal in stressed animals. Maternally separated animals displayed greatly decreased ileal mucin gene expression which was further decreased by exposure to adult stress. Maternal probiotic intervention decreased neonatal ileal MUC2 gene expression. In adulthood however, maternal probiotic intervention reversed the decline in mucin gene expression of stressed males. Collectively the studies presented in the current thesis are the first to demonstrate the influence of maternal probiotic intervention on the neuroendocrine, immune and gut function in a rat model of irritable bowel syndrome. Maternal probiotic intervention exhibited mixed positive and negative effects on brain, immune and gut function, depending on age, gender and stress protocol applied. By modifying the probiotic preparations utilised (e.g., changes in the composition, dose and method of delivery) and optimising time of use, it might be possible to improve this approach to minimise the adverse outcomes. It is clear however, that maternal probiotic intervention may be a viable means to improve brain-gut outcome in ‘at risk’ neonates exposed to stress in early life and at increased risk of IBS in later life.
- Subject
- early life stress; irritable bowel syndrome; rat models; probiotic; brain immune gut axis; neonatal stress
- Identifier
- http://hdl.handle.net/1959.13/937488
- Identifier
- uon:12569
- Rights
- Copyright 2013 Javad Barouei
- Language
- eng
- Full Text
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| View Details Download | ATTACHMENT02 | Thesis | 1 MB | Adobe Acrobat PDF | View Details Download |