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Astbury, Stuart M. (2016) The influence of maternal diet on intestinal adaptation in the mother and offspring. PhD thesis, University of Nottingham.

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Abstract

The effect of maternal nutrition on fetal and offspring growth and risk of disease in later life is well established. Animal models have shown that the small intestine can be preferentially affected by growth restriction compared with other organs, yet the effect of maternal diet on gastrointestinal (GI) development has not been well studied. Furthermore, both the maternal GI tract and microbiome undergo significant adaptations during pregnancy in response to the increased nutritional demands of the growing fetus, which may be further modulated by the maternal diet.

Inadequate development of the GI tract may result in an increase in intestinal permeability, as demonstrated in inflammatory bowel diseases. Compromised gut barrier function has been linked to the development of obesity through the passage of endotoxin on Gram-negative bacteria leading to low-level inflammation of the liver and adipose tissue. The aim of this thesis was to use two animal models of maternal dietary manipulation that are representative of suboptimal nutrition characterised by the nutritional excess of macronutrients found in many Western diets. The effect of either fat in the form of palm oil and carbohydrate in the form of fructose were therefore examined with particular focus on the gut. This was undertaken in a pig model to examine the effects around the time of birth and in the juvenile offspring, whilst in a rat model both the mothers and offspring were studied.

Addition of 10% fructose to drinking water in two generations of pregnant Wistar rats induced impaired glucose tolerance and raised serum triglycerides, but only in the second generation. Sequencing of the maternal microbiome in first generation dams through pregnancy revealed significant changes in microbial diversity from pre-mating to late pregnancy, both between and within dams. Consumption of the fructose diet led to further changes in microbial diversity. Offspring of fructose-fed mothers were growth restricted and had significantly shorter small intestines compared to controls. Changes in gene expression in the ileum and jejunum were indicative of raised intestinal permeability in second-generation dams, and included the epithelial tight junction genes occludin (OCLN), claudin (CLDN) and junctional adhesion molecule (JAM). In both generations the fructose diet significantly upregulated glucose transporters 2 and 5, and sodium-glucose linked transporter 1 in the ileum and jejunum suggesting that a relatively low level supplementation of fructose gradually increases the absorptive capacity of the small intestine for both glucose and fructose. This may explain the significantly impaired glucose tolerance and insulin resistance observed in second-generation offspring.

To study maternal fat supplementation, sows were fed a standard commercial diet supplemented with palm oil (6.6% added to commercial feed) throughout gestation. Median birth weight offspring born to fat supplemented mothers sampled at 7 days demonstrated no growth restriction, but significant downregulation in OCLN, CLDN and JAMA expression, suggesting increased intestinal permeability. No changes in offspring body composition were observed at either time point, and effects on gene expression did not persist up to 6 months of age.

In conclusion, a suboptimal diet through pregnancy in which macronutrient composition is raised has the potential to compromise gut function in the mother and offspring. The magnitude of effect can however be temporary and dependent on the animal model used as well as the macronutrient targeted.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Bell, R.C. Mostyn, A. Sharkey, D. Symonds, M.E.
Keywords:	Gastrointestinal adaptation, Pregnancy, Developmental physiology, Fructose, Maternal nutrition
Subjects:	Q Science > QP Physiology
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	31390
Depositing User:	Astbury, Stuart
Date Deposited:	19 Jul 2016 06:40
Last Modified:	12 Apr 2023 09:36
URI:	https://eprints.nottingham.ac.uk/id/eprint/31390

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