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.

新陈代谢先天性缺陷（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，无论是内部还是外部因素，并超越传统的生化与遗传缺陷概念。在此背景下，在众多影响代谢通量因素中，如饮食、生活方式、抗生素、外来化合物、感染病原体之外，个体的肠道菌群亦应予以考虑。健康的肠道菌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的患者接受特殊饮食，这是这些疾病的主要治疗方法。因此，IEMs成为评估特定膳食模式（就宏量营养素组成和营养品质而言）如何与特定临床表型（“肠表型”）相关的理想模型。在本综述中，我们旨在报告肠道菌群失调（IEMs患者中报告的一种状况）与促炎状态之间可能存在的联系，这通过改变的“肠道-肝脏”跨对话网络和主要氧化应激来实现，进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，应更加关注营养状况评估以及可能的合并症的起始的临床和生化征象，以改善IEMs患者的长期福祉。平衡的肠道生态系统已被证明对患者的健康有积极的贡献，其扰乱可能影响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，实现肠道微生态平衡，可能代表这些复杂疾病的一种预防和治疗策略。