EFFECT OF DIET THERAPY ON GUT MICROBIOME IN RARE GENETIC DISEASES

In the last decades, several studies have explored the human microbiota in different body niches, notably in the gastrointestinal tract. The gut microbiota has been recognized as an additional organ that co-evolves with humans and interacts with host physiology. The gut microbiota plays a key role in the host metabolism and the extraction of energy from food. Diet is the strongest factor shaping the gut microbiota: differences in macronutrient intake may select the growth of specific microbial taxa. Indeed, the diet provides different substrates such as undigested carbohydrates for fermentation, affecting the composition of the gut microbiota and, consequently, the production of microbial metabolites. Short chain fatty acids (SCFAs), mainly acetate, propionate, and butyrate, are the major end products of anaerobic fermentation by gut microbes. Modifications in the proportions of the gut microbes and, consequently, the production of SCFAs have been suggested to play a role in several pathological conditions. If the diet is modifiable to stimulate the growth of beneficial microbes, it could represent a target for prevention and treatment of a possible dysbiosis. In congenital metabolic disorders such as phenylketonuria (PKU) and glycogen storage disease (GSD), diet is considered the mainstay for the treatment of the pathology. PKU diet is based on the restriction of phenylalanine intake and the supplementation of essential amino acids and micronutrients. PKU diet is similar to a vegan alimentation since all the animal products are excluded. GSD dietary management provides the intake of slow-release carbohydrates to prevent hypoglycaemia and limits the assumption of simple sugars. In this research, we aimed to analyze the impact of dietary therapy on the composition of the gut microbiota and the production of SCFAs in two congenital metabolic disorders (PKU and GSD). PKU and GSD diseases showed an alteration of the gut microbiome. If diet represents the only treatment of the disease and is not modifiable, a personalized intervention to restore a healthy gut microbiome is to consider. Nowadays, the attention is focused on the supplementation of probiotics and prebiotics.