Data_Sheet_1_Dysbiosis, Host Metabolism, and Non-communicable Diseases: Trialogue in the Inborn Errors of Metabolism.docx

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.

代谢性先天性疾病（IEMs）构成一个复杂的系统模型，亟需转变研究方法，以探究调节该系统的主要因素，无论其为内部或外部因素，并超越传统对生化缺陷和遗传缺陷的概念。在此背景下，在影响代谢通量的既定因素中，例如饮食、生活方式、抗生素、外来化合物、感染病原体之外，个体的肠道微生物群也应予以考虑。健康的肠道微生物群通过向人类宿主提供独特的代谢功能，有助于维持人类健康。许多患有IEMs的病患需要遵循特殊的饮食，这是这些疾病的主要治疗方法。因此，IEMs成为评估特定饮食模式（就宏量营养素组成和营养质量而言）如何与特定临床表型（“肠表型”）相关的微生物群特征之间关系的一个良好模型。在本综述中，我们旨在报告肠道菌群失调（一种在IEMs患者中报道的条件）与促炎状态之间的可能联系，这是通过改变的“肠-肝”交流网络和主要的氧化应激实现的，从而影响患者的健康状况，增加非传染性疾病（NCDs）的风险。基于此，应更加关注对营养状况的评估以及可能并发症的起始的临床和生化征兆，以改善IEMs患者的长期福祉。平衡的肠道生态系统已被证实对患者的健康产生积极贡献，其紊乱可能影响IEMs个体的临床谱。为此，通过改善膳食产品和混合物的质量，使用益生菌、益生元和后生元，达到肠道的平衡状态，可能代表这些复杂疾病中既预防又治疗的策略。