Functional effects of dietary proteins and bioactive peptides on satiety and metabolic response in humans

Gut-brain axis is a crucial hub of the food intake and energy balance regulation. Dichotomy between homeostatic and non-homeostatic/hedonic systems should be replaced by a larger, highly interactive system that unifies homeostasis with reward, cognition, and emotion. Understanding the integrative role of the CNS in energy and reward homeostasis has become increasingly important considering the prevalence of obesity and functional gastrointestinal disorders (FGIDs). The GIT is the largest endocrine organ in the human body and it represents the gateway for communication between the human body and the external environment. Distress (i.e. inflammation) or adaptations in the communication of sensory information may contribute to the development or maintenance of disease. Several diseases such as celiac disease, Crohn’s disease, type 1 diabetes and some food allergies, are known to increase the GIT mucosa permeation of macromolecules. As reported in Chapter 2 FGIDs are classified as morphologic and physiological abnormalities often occurring in combination with motility disturbance, visceral hypersensitivity, as well as altered mucosa, immune function, gut microbiota and CNS processes. The incidence of FGIDs among population is about 11%. Some of the symptoms reported for the functional dyspepsia are similar to those of non-celiac gluten sensitivity such as postprandial fullness, early satiety, epigastric pain, and epigastric burning. These symptoms may appear isolated or combined after consumption of specific foods. The nutritional consequence of this symptomatology is that people arbitrarily exclude from diet the foods which are mainly associated with the symptoms such as spicy foods, high-fat meals, dairy products or cereal-based foods. Life-lasting dietary exclusions may cause nutritional deficiency as well as metabolic adaptation that may be even worst of the previous symptomatology. This is the reason why in the case of a specific food/nutrient-induced disorder the usual dietetic approach is the exclusion from the diet of the specific food/nutrient for a certain period and a slow re-introduction in the follow-up period. The exclusion from the diet of gluten represents the cure only for people with celiac disease but literature was still lacking on the knowledge of the metabolic response to a gluten-free meal in patients with celiac disease compared to healthy subjects. The human study reported in Chapter 3 aimed at filling that gap of knowledge. From a dietetic perspective, the effect of a meal is more relevant in exerting metabolic responses than a single nutrient/food. Celiac subjects (CD) at the diagnosis or on a gluten free diet since 12 months and healthy subjects consumed a standard gluten-free meal and the post-prandial blood glucose and hormone response as well as appetite feelings were monitored. The main results of the study was that CD showed a lower postprandial blood glucose response than healthy subjects with a lower response of GLP-1, GIP and insulin. The different hormonal status was associated with a different evolution of the post-prandial hunger sensation that was higher in CD at diagnosis than in the others. These findings suggested that CD subjects after more than 1 year on a gluten free diet did not recover a complete functionality of the intestine and this might determine an adaptive hormone postprandial response that may influence post-prandial appetite sensations and insulin resistance over long period. From a food science and nutrition perspective, some bioactive compounds are present in foods and may be effective in the control of appetite, intestinal inflammation and glycaemia. In this thesis the potential of food bioactive peptides contained in milk proteins, casein and soy hydrolysates towards appetite, inflammation and glycaemia was tested and described in the human study in Chapter 4, and in in vitro studies of Chapter 5 and 6, respectively. In Chapter 4 two beverages, one enriched with milk proteins and one with carbohydrates (control) were developed and a human study with women consuming the beverage after an exercise session was carried out aiming at evaluating the effect of the beverages on the energy intake at the subsequent dinner. Data showed that the milk protein-enriched beverage was able to influence hunger sensation and reduce energy intake at subsequent meal only in women having a strong cognitive control of eating behaviour. In Chapter 5 casein and soy hydrolysates were tested in Caco-2 cells cultivated in a normal condition and in the presence of TNF-α to induce intestinal inflammation. Data showed that digested casein and soy protein hydrolysates positively influenced cells viability, particularly in inflamed condition. Data about monolayer integrity (TEER) showed an absence of irreversible damage at the normal and inflamed cell monolayer when it was treated with digested samples. In Chapter 6 casein (CH) and soy (SH) protein hydrolysates were tested as functional ingredients for glycaemia control, through inhibition of Dipeptidyl peptidase-IV (DPP-IV) activity. This study showed that when used in a model food CH and SH loosed their inhibitory activity against DPP-IV possibly because of other food components that could hide the bioactivity of CH and SH at the doses used in the model food. This scenario highlights the importance of validation of efficacy of new foods/whole meals both in vitro to assess the potential functionalities before performing human studies as well as in vivo in a well-characterized population. Indeed, growing evidence shows that the effect of food on wellness and dietary behaviour may be also influenced by psychological attitude of people as well as by gut microbiota reactivity to a food/diet. In the context of new foods/diets to tackle obesity and FGIDs the gut-brain interconnection is central and should be better targeted both at the step of the food design and validation