Dietary Manipulation at Pre-Conception and During Development Influence Metabolism and Gut Microbiota in Rats
Date
2021-02-01
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Abstract
Background. Obesity is a complex disease, modulated by a plethora of factors, including gut microbiota, early post-natal nutrition, parental diet and epigenetics. Objective. This dissertation examines how dietary manipulation during the early post-natal period and during pre-conception alters metabolic, microbial and epigenetic outcomes in rats. Specifically, the objectives were to determine: 1) the impact of human milk oligosaccharide (HMO) supplementation on health status in weanling rats; 2) the impact of a paternal high protein (HP) diet on offspring metabolic health; 3) whether supplementation of a methyl donor cocktail (HF/S+M) before conception attenuates the deleterious metabolic and epigenetic effects of a paternal high fat/ sucrose diet intergenerationally; 4) the impact of paternal prebiotic consumption on microbial and metabolic outcomes in fathers and offspring. Methods. 1) Weanling male and female rats consumed 2’Fucosyllactose and 3’Sialylactose HMO-fortified diet for 8 weeks. Fathers consumed 2) a diet high in protein, 3) a high fat/ sucrose diet fortified with a methyl donor cocktail of betaine, choline, folic acid and vitamin B12, or 4) a high prebiotic fiber diet. All three paternal studies underwent their dietary intervention for 9 weeks. Offspring consumed a control diet for 13 weeks. Anthropometric, glucocentric and gut microbiota outcomes were measured in all four studies. Results. The primary findings include: HMO supplementation improved intestinal permeability, gut barrier function, and gut microbial composition in females while reducing weight gain and inflammatory cytokines in males; 2) Paternal HP diet reduced adiposity and altered epigenetic markers intergenerationally. Offspring had improved insulin sensitivity; 3) Paternal HF/S+M intake improved paternal reproductive outcomes and intergenerational gut microbial, epigenetic and metabolic outcomes; 4) Paternal prebiotic intake improved paternal gut microbiota with lesser effects in offspring. Conclusion. Our results provide evidence of early post-natal HMO supplementation and paternal HP, HF/S+M and prebiotic intake, as important modulators of gut microbial, epigenetic and metabolic outcomes.
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Nutrition, Genetics, Metabolism, Gut Microbiota, Epigenetics, Obesity, Human Milk Oligosaccharides, Paternal Programming
Citation
Chleilat, F. (2021). Dietary Manipulation at Pre-Conception and During Development Influence Metabolism and Gut Microbiota in Rats (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.