Preserving the intestinal epithelial integrity improves metabolic syndrome
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Metabolic disorders including obesity and its comorbidities are major health problems in the United States where western diets, rich in fat, are widely consumed. Recent studies have shown that increased gastrointestinal (GI) tract permeability in response to high fat (HF) allows for translocation of pro-inflammatory bacterial products to the circulation and promotes systemic inflammation. Chronic inflammation plays a key role in the development of metabolic disorders. HF diet-induced GI inflammation impairs intestinal barrier integrity. Although the causal relationship between increased gut permeability and systemic inflammation has attracted recent interest in the metabolic area, there is little data available on strategies to restore gut epithelial barrier integrity. Thus, the objective of this dissertation is to investigate potential candidates to preserve GI barrier integrity in response to a HF challenge. I hypothesized that preserving the GI barrier integrity will prevent systemic inflammation and consequent deleterious effects in rats fed HF diets. For all studies, Wistar rats were fed a HF diet for 7 to 8 wk to induce inflammation and supplemented with either a bioactive food (blueberry, Chapter 2) or a probiotic (Chapter 3). For the probiotic study, I employed a novel approach of microencapsulation to enhance the efficacy of probiotic delivery to the distal gut. Microbiota composition, intestinal integrity, inflammation, and glucose homeostasis were assessed. In the first study (Chapter 2), blueberry supplementation decreased inflammation and insulin resistance in HF-fed rats in conjunction with compositional changes in gut microbiota and improved gut integrity. These changes may have prevented bacterial pro-inflammatory product translocation, resulting in reduced systemic inflammation and improved hepatic insulin sensitivity in HF-fed rats. In another study (Chapter 3), although the efficacy of microencapsulation was not verified, probiotic (Lactobacillus paracasei subsp. paracasei)-induced improvements in metabolic profiles in HF-fed rats were confirmed to be associated with compositional changes in gut microbiota and improved gut barrier integrity. These effects were primarily associated with alleviation of local and systemic inflammation. Collectively, the studies of this dissertation suggest that preserving the intestinal barrier improves inflammatory conditions in HF-fed rodents and identify potential dietary interventions for the prevention of obesity-associated metabolic abnormalities.