医学遗传学2.0:导致人类慢病的主因可能首先是人体共生微生物基因异常,其次才是人类基因异常

Medical genetics 2.0:Human chronic diseases-associated genes are primarily the genes of human symbiotic microorganisms and secondarily the human genes

当前慢病高发的现实对“健康中国2030”战略目标的实现提出了巨大挑战。虽然众多医疗机构和政府管理部门付出巨大努力,然而如果仍然沿袭现有慢病防控模式和医疗改革理念,恐怕很难在近期内实现慢病防控的突破,迫切需要引入新思路,才有可能破解慢病高发这个难题。根据近年来国内外大量报道人体共生微生物尤其是肠道菌群与人体多种慢病之间存在密切相关性甚至因果性的研究进展,以及在此启发下我们实验室通过大量研究发现“饥饿源于菌群”,结合诸多文献报道证明通过调控肠道菌群微生态可改善多种慢病,为“慢病源于菌群”提供了重要依据,从而提出“医学遗传学2.0”(Medical genetics 2.0,MG2.0)的概念,其核心思想是将复杂性疾病(主要指慢病)的致病因素优先归因于人体共生微生物尤其是肠道菌群基因组异常,而人类基因组异常则是跟随前者发生顺应性改变的结果,即人体共生微生物基因组异常是慢病的主要矛盾,人类自身的基因组异常是慢病的次要矛盾,两套基因组通过联立交互作用,最终导致人体慢病持续发展。如果只是通过纠正人类基因组异常,而忽视了纠正菌群基因组异常,则难以从根本上治疗慢病,因为异常的菌群基因组仍然会持续影响人体健康。因此,在慢病防控方面,建议医学遗传学领域的研究重点可向肠道菌群等人体共生微生物领域进行深化,广泛开展以人体共生微生物尤其是肠道菌群基因组为主、人类基因组为辅的人菌双基因组关联分析研究,建立不同慢病的菌群图谱(含基因组学、转录组学、蛋白质组学、代谢组学以及生命组学等相关研究),并研究纠正异常菌群图谱的方法(含靶向肠道菌群的新药研发),为慢病防控找到新出路。

The current situation of high incidence of chronic diseases poses a great challenge to the realization of the strategic goal of“healthy China 2030”.Although many medical institutions and government departments have made great efforts,however if we still persist in the existing chronic disease prevention and control strategy and the concept of medical reform,it is difficult to achieve a breakthrough in the prevention and control of chronic diseases in the near future.There is an urgent need to develop new ideas in this field in order to solve the problem of high incidence of chronic diseases.According to a large number of reports in recent years,there is a close correlation or even causality between human symbiotic microorganisms,especially gut flora and a variety of chronic diseases.Based on these results,our laboratory found that“hunger sensation comes from gut flora”through a large number of clinical studies.Combined with many literature reports,it has been demonstrated that many chronic diseases can be improved by targeting the abnormal gut flora.It thus provides an important basis for“chronic diseases originate from abnormal gut flora”.Accordingly,the concept of“medical genetics 2.0(MG2.0)”is put forward and the core idea of MG2.0 is to attribute the pathogenic factors of complex diseases(mainly chronic diseases)to human symbiotic microorganisms,especially the genomic abnormalities of gut flora,while the human genome abnormality is the result of compliance changes.The main contradiction of chronic diseases is the abnormal genome of gut flora,while the human genome abnormality is the secondary contradiction of chronic diseases.The interaction between these two sets of genomes eventually leads to the continuous development of chronic diseases.If only to correct the human genome but without correcting the genomic abnormality of the gut flora,it is difficult to win the war on chronic diseases fundamentally because the abnormal gut flora genome will continue to affect human health therefore on chronic disease prevention and control.The researches focus on the field of medical genetics should be deepened to human symbiotic microorganisms such as gut flora.The research on the relationship between human genome and human symbiotic microorganism genome is largely needed to establish the gut flora portrait at different levels including genome,transcriptome,proteomics and metabolomics of different chronic diseases.It is important to develop new approaches to correct the breakthrough of abnormal gut flora in order to find a new way to prevent and control chronic diseases.