Nutritional modulation of gut microbiota
(2013)
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- (en) Obesity represents a major public health problem characterized by an excessive accumulation of fat mass and associated with several metabolic disorders, leading to an increased risk of developing diabetes, cardiovascular diseases and even some cancers. During recent years, the gut microbiota has emerged as a central player in the development of obesity and its related alterations. Prebiotic nutrients like dietary inulin-type fructans (ITF) selectively change the gut microbiota composition and numerous studies in rodents have associated this phenomenon to beneficial impact on host metabolism. In this thesis, we studied the mechanisms underlying the positive influence of ITF on host metabolism and adiposity, in pathological conditions such as obesity and diabetes. This work was divided in two main sections. The first part was an experimental approach focused on the effects of ITF prebiotics on adipose tissue metabolism in diet-induced obese mice. We confirmed that one of the mechanisms responsible for the excessive accumulation of fat mass upon high-fat feeding was an activation of one key regulator of adipogenesis (i.e. peroxisome proliferator-activated receptor gamma, PPARg), associated with a modulation of expression of one specific G-protein-coupled receptor binding bacterial metabolites, namely GPR43. ITF prebiotics, beyond their impact on gut microbiota, were able to counteract the diet-induced fat mass development but this effect appeared to be only partially dependent on the modulation of PPARg activity. However, when combined to an antidiabetic drug known as an activator of PPARg, ITF prebiotics decreased adiposity and improved metabolism without avoiding the beneficial impact of the PPARg agonist on glucose homeostasis. Further studies are needed to completely understand the mechanisms responsible for the beneficial effect linked to ITF prebiotics and antidiabetic drug association. The aim of the second part of this thesis was to study the impact of ITF prebiotics on gut microbiota and overall metabolism in obese individuals. Therefore, we performed a double blind and randomized study in obese women who were allocated to the prebiotic group or the placebo group for 3 months. We demonstrated that prebiotics induced selective changes in gut microbiota composition (e.g. important increase in bifidobacteria) that were associated with changes in fat mass, inflammation and some metabolites potentially implicated in the development of obesity and related disorders. However, probably due to the small number of patients, we did not observe any significant change in body weight, glucose and lipid homeostasis. Nonetheless, our study may be considered as a prerequisite to better define the target population and patients characteristics for further larger intervention studies. Altogether, these results suggest ITF prebiotics as nutrients that should be considered in the management of obesity and diabetes in rodents but also in humans.
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Dewulf, E. (2013). Nutritional modulation of gut microbiota. https://hdl.handle.net/2078.5/206100