Dysbiosis, Host Metabolism, and Non-communicable Diseases: Trialogue in the Inborn Errors of Metabolism

Abstract

Inborn errors of metabolism (IEMs) represent a complex system model, in need of a shift of approach exploring the main factors mediating the regulation of the system, internal or external and overcoming the traditional concept of biochemical and genetic defects. In this context, among the established factors influencing the metabolic flux, i.e., diet, lifestyle, antibiotics, xenobiotics, infectious agents, also the individual gut microbiota should be considered. A healthy gut microbiota contributes in maintaining human health by providing unique metabolic functions to the human host. Many patients with IEMs are on special diets, the main treatment for these diseases. Hence, IEMs represent a good model to evaluate how specific dietary patterns, in terms of macronutrients composition and quality of nutrients, can be related to a characteristic microbiota associated with a specific clinical phenotype (“enterophenotype”). In the present review, we aim at reporting the possible links existing between dysbiosis, a condition reported in IEMs patients, and a pro-inflammatory status, through an altered “gut-liver” cross-talk network and a major oxidative stress, with a repercussion on the health status of the patient, increasing the risk of non-communicable diseases (NCDs). On this basis, more attention should be paid to the nutritional status assessment and the clinical and biochemical signs of possible onset of comorbidities, with the goal of improving the long-term wellbeing in IEMs. A balanced intestinal ecosystem has been shown to positively contribute to patient health and its perturbation may influence the clinical spectrum of individuals with IEMs. For this, reaching eubiosis through the improvement of the quality of dietary products and mixtures, the use of pre-, pro- and postbiotics, could represent both a preventive and therapeutic strategy in these complex diseases.

Are Phe-Free Protein Substitutes Available in Italy for Infants with PKU All the Same?

“…No other biotics are added to the analysed PS for PKU infants. Given the known status of gut dysbiosis in PKU following Phe-restricted diet [ 43 ], the early modulation of the gut microbiota, also achievable through the addition of biotics (e.g., HMOs, GOS/FOS respecting 9:1 ratio) to infant protein substitutes, could be considered to have beneficial effects on dysbiosis and microbiota–gut–liver–brain axis, although results from clinical intervention studies are needed. A systematic review of the committee on Nutrition of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) on supplementation of infant formula with probiotics and/or prebiotics highlighted the absence of safety concerns in relation to growth and development, but more experimental research is needed [ 44 ].…”

Special Diets in Infants and Children and Impact on Gut Microbioma

“…The management of these diseases usually consists of an exclusion dietary regimen that can reduce gut microbial biodiversity by promoting a state of dysbiosis [ 162 , 163 ]. Hence, IEMs represent a good model to evaluate how special diets are related to specific bacteria profiles that, in turn, could be associated with a characteristic clinical phenotype (“enterophenotype”) [ 164 ].…”

Impact of helminth–microbiome interactions on childhood health and development—A clinical perspective

“…Dysbiosis in the gut has been associated with obesity and metabolic syndromes in children in many clinical studies conducted worldwide 134–143 . While these alterations in GM composition could also be due in part to the altered diet or metabolic state of obese children, a longitudinal study in Norway demonstrated that GM composition at 2 years of age was predictive of BMI at age 12 144 .…”

“…133 Dysbiosis in the gut has been associated with obesity and metabolic syndromes in children in many clinical studies conducted worldwide. [134][135][136][137][138][139][140][141][142][143] While these alterations in GM composition could also be due in part to the altered diet or metabolic state of obese children, a longitudinal study in Norway demonstrated that GM composition at 2 years of age was predictive of BMI at age 12. 144 Furthermore, another study identified gut dysbiosis in prediabetic children, 17 suggesting that alterations in GM composition can also precede the onset of metabolic syndromes.…”