双脑模型假说—由肠道菌群微生态构建的“菌脑”可能是人体对物质记忆的“第二大脑”
|
摘要
如何看待细菌这种虽然微小、然而却与人类生活密切相关的生命体,对于理解生命的起源和动机具有重要意义。大量文献报道,受"人类第二基因组"编码的人体共生微生物尤其是肠道菌群与多种慢病如肥胖、糖尿病、自闭症甚至抑郁症等密切相关,凸显出肠道菌群对健康的重要性。在国内外相关研究启发下,我们实验室通过大量研究发现"饥饿源于菌群",并在反向验证的基础上提出"菌心说"学说,认为肠道菌群为人体编码饥饿基因,是推动人体(和动物)因饥饿而被迫摄食的客观原因,进而提出"菌心进化论",在认可人体(和动物)以中空的消化道结构为肠道菌群提供栖息场所的基础上,认为动物的进化过程也受到肠道菌群所施加的饥饿压力而发展,并表现为"人菌共生"的彼此依赖关系。由于人脑主要以葡萄糖为能源、而肠道菌群则能够以自然界多种碳源为能源,由此引发作者提出这样的科学问题,即由肠道菌群组成的"菌脑"会是人体对物质记忆的"第二大脑"吗?在进一步分析的基础上,我们逐渐形成"双脑模型(two-brain model,TBM)"的新认识,即"(肠道)菌群承载物质记忆而构成人体对物质需求的大脑"以及"人脑承载符号记忆和逻辑推理而构成意识和思维(乃至精神追求)的大脑","物质记忆大脑"和"意识处理大脑"依托于人体,并通过肠脑轴等方式实时对话通讯,分别实现对人体的物质操控(如摄食动机和物质依赖)和意识调控(如思考过程和精神意志),将有助于从物质和意识相互关系的层次深入理解如何重构、重建、重塑正确的"人菌关系",深刻理解"吃五谷"与"得百病"的关系,推动"健康中国"战略的早日实现。
How to recognize the microbiota especially the bacteria,which are tiny but closely related to human life,is of great significance for understanding the origin and motivation of life. A large number of literature has documented that human symbiotic microorganisms,especially the gut flora coded by the "human second genome",are closely related to a variety of chronic diseases such as obesity,diabetes,autism and even depression,highlighting the importance of gut flora for human health. Inspired by relevant studies home and abroad in recent years,our laboratory found that"hunger sensation comes from gut flora"through a large number of studies,and put forward the"gut floracentric theory"on the basis of reverse validation. It believes that gut flora code the starvation gene of human body,which is the objective cause of human(and animal) being forced to eat food because of hunger,and then develop the"gut flora-centric theory of evolution". Based on the hollow structure of the digestive tract,which provides a habitat for gut flora,it is believed that the evolution of animals is also developed under the hunger stress exerted by gut flora,and that the evolution of animals is manifested by the interdependence of "symbiosis of host and gut flora". Because the human brain mainly obtain energy from glucose,while gut flora from a variety of natural carbon sources,which raise us to ask such a scientific question: will the "bacterial brain"composed of gut flora be the"second brain"of human body for material memory on the basis of further analysis,we have gradually formed a new understanding of the "two-brain model(TBM) "which means "gut flora carries material memory and constitutes the human body's brain for material needs",while the human brain carries symbolic memory and logical reasoning thereby constituting the brain of consciousness and thinking(and even spiritual pursuit). The "two brains"rely on the human body and communicates with each other in real time by means of intestinal-brain axis,which realizes material manipulation(such as feeding motivation and material dependence) and conscious regulation(such as thinking process and spiritual will),respectively. It will help us to understand how to reconstruct and reshape the correct"human-bacterial relationship"between material and consciousness,and to deeply understand the etiology of chronic diseases from eating behaviors and disorder of gut flora in order to promote the early realization of the strategy of "healthy China".
How to recognize the microbiota especially the bacteria,which are tiny but closely related to human life,is of great significance for understanding the origin and motivation of life. A large number of literature has documented that human symbiotic microorganisms,especially the gut flora coded by the "human second genome",are closely related to a variety of chronic diseases such as obesity,diabetes,autism and even depression,highlighting the importance of gut flora for human health. Inspired by relevant studies home and abroad in recent years,our laboratory found that"hunger sensation comes from gut flora"through a large number of studies,and put forward the"gut floracentric theory"on the basis of reverse validation. It believes that gut flora code the starvation gene of human body,which is the objective cause of human(and animal) being forced to eat food because of hunger,and then develop the"gut flora-centric theory of evolution". Based on the hollow structure of the digestive tract,which provides a habitat for gut flora,it is believed that the evolution of animals is also developed under the hunger stress exerted by gut flora,and that the evolution of animals is manifested by the interdependence of "symbiosis of host and gut flora". Because the human brain mainly obtain energy from glucose,while gut flora from a variety of natural carbon sources,which raise us to ask such a scientific question: will the "bacterial brain"composed of gut flora be the"second brain"of human body for material memory on the basis of further analysis,we have gradually formed a new understanding of the "two-brain model(TBM) "which means "gut flora carries material memory and constitutes the human body's brain for material needs",while the human brain carries symbolic memory and logical reasoning thereby constituting the brain of consciousness and thinking(and even spiritual pursuit). The "two brains"rely on the human body and communicates with each other in real time by means of intestinal-brain axis,which realizes material manipulation(such as feeding motivation and material dependence) and conscious regulation(such as thinking process and spiritual will),respectively. It will help us to understand how to reconstruct and reshape the correct"human-bacterial relationship"between material and consciousness,and to deeply understand the etiology of chronic diseases from eating behaviors and disorder of gut flora in order to promote the early realization of the strategy of "healthy China".
引文
[1] Bckhed F,Ding H,Wang T,et al. The gut microbiota as an environmental factor that regulates fat storage[J]. Proc Natl Acad Sci USA,2004,101(44):15718-15723.
[2] Ussar S,Griffin N W,Bezy O,et al. Interactions between gut microbiota,host genetics and diet modulate the predisposition to obesity and metabolic syndrome[J]. Cell Metab,2015,22(3):516-530.
[3] Boerner B P,Sarvetnick N E. Type 1 diabetes:role of intestinal microbiome in humans and mice[J]. Ann N Y Acad Sci,2011,1243:103-118.
[4]梁姗,王涛,胡旭,等.微生物与行为和精神疾病[J].心理科学进展,2012,20(1):75-97.
[5] Zheng P,Zeng B,Zhou C,et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism[J]. Mol Psychiatry,2016,21(6):786-796.
[6] Hsiao E Y,Mc Bride S W,Hsien S,et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders[J]. Cell,2013,155(7):1451-1463.
[7] Sender R,Fuchs S,Milo R. Are we really vastly outnumbered revisiting the ratio of bacterial to host cells in humans[J]. Cell,2016,164(3):337-340.
[8] Qin J J,Li R Q,Raes J,et al. A human gut microbial gene catalogue established by metagenomic sequencing[J]. Nature,2010,464(7285):59-65.
[9] Eckburg P B,Bik E M,Bernstein C N,et al. Diversity of the human intestinal microbial flora[J]. Science,2005,308(5728):1635-1638.
[10] Arumugam M,Raes J,Pelletier E,et al. Enterotypes of the human gut microbiome[J]. Nature,2011,473(7346):174-180.
[11]郑智俊,黄云,秦楠,等.人体肠道宏基因组生物信息分析方法[J].微生物学报,2018,58(11):2020-2032.
[12]亓合媛,孙清岚,马俊才,等.微生物组大数据管理与分析[J].微生物学报,2017,57(6):932-941.
[13] Bckhed F,Ding H,Wang T,et al. The gut microbiota as an environmental factor that regulates fat storage[J]. Proc Natl Acad Sci USA,2004,101(44):15718-15723.
[14] Ridaura V K,Faith J J,Rey F E,et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice[J].Science,2013,341(6150):1241214-1241226.
[15] Ley R E,Bckhed F,Turnbaugh P,et al. Obesity alters gut microbial ecology[J]. Proc Natl Acad Sci USA,2005,102(31):11070-11075.
[16] Zhao L P. The gut microbiota and obesity:from correlation to causality[J]. Nat Rev Microbiol,2013,11(9):639-647.
[17]张成岗,巩文静.基于饥饿源于菌群的新发现将引发慢病防控突破性进展[J].科技导报,2017,35(21):43-48.
[18]张成岗.当前慢病防控困境迫切呼唤新医学和菌心说[J].科技导报,2015,33(22):106-111.
[19]张成岗.青蒿素研发及屠呦呦获得诺贝尔奖的启示[J].科技导报,2015,33(20):86-89.
[20]张成岗.《新医学·菌心说·云医院》[M].北京:中医古籍出版社,2016:1-67.
[21]任青河,黄江南,黄荣杰,等.柔性辟谷技术改善高血压的初步研究[J].中国食物与营养,2017,23(8):70-75.
[22]巩文静,黄清健,高大文,等.柔性辟谷技术在青年人群体重控制中的应用[J].军事医学,2016,40(8):651-656.
[23]高大文,巩文静,李志慧,等.柔性辟谷技术对早期糖尿病患者高血糖改善作用的初步研究[J].中国食物与营养,2018,24(4):76-79,83.
[24]卢宁,巩文静,李志慧,等.柔性辟谷技术减重及改善血压血糖的初步研究[J].中国民康医学,2018,30(18):4-7.
[25]张成岗,巩文静.柔性辟谷:一种可改善肥胖及相关慢性病的新技术[J].中国民康医学,2018,30(6):100-102.
[26] Gong W J,Sun C Q,Teng S Z,et al. Evaluation of a novel fasting approach using plant polysaccharides per meal in human symbionts[J]. Intergr Clin Med,2018,2(2):1000123-1000134.
[27] Zhang C G. The Gut Flora-Centric Theory Based on the New Medical Hypothesis of “Hunger Sensation Comes from Gut Flora”:A New Model for Understanding the Etiology of Chronic Diseases in Human Beings[J]. Austin Intern Med,2018,3(3):1030-1036.
[28] Bakken J S,Borody T,Brandt L J,et al. Treating Clostridium difficile infection with fecal microbiota transplantation[J].Clin Gastroenterol Hepatol,2011,9(12):1044-1049.
[29] Drekonja D,Reich J,Gezahegn S,et al. Fecal microbiota transplantation for clostridium difficile infection:a systematic review[J]. Ann Intern Med,2015,162(9):630-638.
[30]张成岗,巩文静,李志慧,等.医学3. 0与健康管理2. 0将促进健康中国战略的早日实现[J].转化医学电子杂志,2018,5(12):108-111.
[31]孔芳,洪康进,徐航,等.基于啮食泡沫塑料黄粉虫肠道菌群中聚苯乙烯生物降解的探究[J].微生物学通报,2018,45(7):1438-1449.
[32] Yang J,Yang Y,Wu W M,et al. Evidence of polyethylene biodegradation by bacterial strains from the guts of plastic-eating waxworms[J]. Environ Sci Technol,2014,48(23):13776-13784.
[33] Lee K,Vuong H E,Nusbaum D J,et al. The gut microbiota mediates reward and sensory responses associated with regimen-selective morphine dependence[J]. Neuropsychopharmacology,2018,43(13):2606-2614.
[34]张成岗,巩文静,李志慧,等.菌心进化论:一种对于动物进化的新理解[J].生物信息学,2018,16(4):203-213.
[35]张成岗,巩文静,李志慧,等.基于对人体结构与功能的新认识将促进健康现代化[C].第十六期中国现代化研究论坛论文集,2018:71-77.
[36] Fetissov S O. Role of the gut microbiota in host appetite control:bacterial growth to animal feeding behaviour[J]. Nature reviews Endocrinology,2017,13(1):11-25.
[37] Carter M E,Soden M E,Zweifel L S,et al. Genetic identification of a neural circuit that suppresses appetite[J]. Nature,2016,503(7474):111-114.
[38] Atasoy D,Betley J N,Su H H,et al. Deconstruction of a neural circuit for hunger[J]. Nature,2012,488(7410):172-177.
[39] Hameed S,Dhillo W S,Bloom S R. Gut hormones and appetite control[J]. Gastroenterology,2009,132(6):2116-2130.
[40]巩文静,张岩,郭素霞,等.医院体检中心基于柔性辟谷技术进行全链条闭环式体质量管理工作模式的初步研究[J].实用临床医药杂志,2019,23(5):7-10,15.
[41] Janssen S,Depoortere I. Nutrient sensing in the gut:new roads to therapeutics[J]. Trends in Endocrinology&Metabolism Tem,2013,24(2):92-100.
[2] Ussar S,Griffin N W,Bezy O,et al. Interactions between gut microbiota,host genetics and diet modulate the predisposition to obesity and metabolic syndrome[J]. Cell Metab,2015,22(3):516-530.
[3] Boerner B P,Sarvetnick N E. Type 1 diabetes:role of intestinal microbiome in humans and mice[J]. Ann N Y Acad Sci,2011,1243:103-118.
[4]梁姗,王涛,胡旭,等.微生物与行为和精神疾病[J].心理科学进展,2012,20(1):75-97.
[5] Zheng P,Zeng B,Zhou C,et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism[J]. Mol Psychiatry,2016,21(6):786-796.
[6] Hsiao E Y,Mc Bride S W,Hsien S,et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders[J]. Cell,2013,155(7):1451-1463.
[7] Sender R,Fuchs S,Milo R. Are we really vastly outnumbered revisiting the ratio of bacterial to host cells in humans[J]. Cell,2016,164(3):337-340.
[8] Qin J J,Li R Q,Raes J,et al. A human gut microbial gene catalogue established by metagenomic sequencing[J]. Nature,2010,464(7285):59-65.
[9] Eckburg P B,Bik E M,Bernstein C N,et al. Diversity of the human intestinal microbial flora[J]. Science,2005,308(5728):1635-1638.
[10] Arumugam M,Raes J,Pelletier E,et al. Enterotypes of the human gut microbiome[J]. Nature,2011,473(7346):174-180.
[11]郑智俊,黄云,秦楠,等.人体肠道宏基因组生物信息分析方法[J].微生物学报,2018,58(11):2020-2032.
[12]亓合媛,孙清岚,马俊才,等.微生物组大数据管理与分析[J].微生物学报,2017,57(6):932-941.
[13] Bckhed F,Ding H,Wang T,et al. The gut microbiota as an environmental factor that regulates fat storage[J]. Proc Natl Acad Sci USA,2004,101(44):15718-15723.
[14] Ridaura V K,Faith J J,Rey F E,et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice[J].Science,2013,341(6150):1241214-1241226.
[15] Ley R E,Bckhed F,Turnbaugh P,et al. Obesity alters gut microbial ecology[J]. Proc Natl Acad Sci USA,2005,102(31):11070-11075.
[16] Zhao L P. The gut microbiota and obesity:from correlation to causality[J]. Nat Rev Microbiol,2013,11(9):639-647.
[17]张成岗,巩文静.基于饥饿源于菌群的新发现将引发慢病防控突破性进展[J].科技导报,2017,35(21):43-48.
[18]张成岗.当前慢病防控困境迫切呼唤新医学和菌心说[J].科技导报,2015,33(22):106-111.
[19]张成岗.青蒿素研发及屠呦呦获得诺贝尔奖的启示[J].科技导报,2015,33(20):86-89.
[20]张成岗.《新医学·菌心说·云医院》[M].北京:中医古籍出版社,2016:1-67.
[21]任青河,黄江南,黄荣杰,等.柔性辟谷技术改善高血压的初步研究[J].中国食物与营养,2017,23(8):70-75.
[22]巩文静,黄清健,高大文,等.柔性辟谷技术在青年人群体重控制中的应用[J].军事医学,2016,40(8):651-656.
[23]高大文,巩文静,李志慧,等.柔性辟谷技术对早期糖尿病患者高血糖改善作用的初步研究[J].中国食物与营养,2018,24(4):76-79,83.
[24]卢宁,巩文静,李志慧,等.柔性辟谷技术减重及改善血压血糖的初步研究[J].中国民康医学,2018,30(18):4-7.
[25]张成岗,巩文静.柔性辟谷:一种可改善肥胖及相关慢性病的新技术[J].中国民康医学,2018,30(6):100-102.
[26] Gong W J,Sun C Q,Teng S Z,et al. Evaluation of a novel fasting approach using plant polysaccharides per meal in human symbionts[J]. Intergr Clin Med,2018,2(2):1000123-1000134.
[27] Zhang C G. The Gut Flora-Centric Theory Based on the New Medical Hypothesis of “Hunger Sensation Comes from Gut Flora”:A New Model for Understanding the Etiology of Chronic Diseases in Human Beings[J]. Austin Intern Med,2018,3(3):1030-1036.
[28] Bakken J S,Borody T,Brandt L J,et al. Treating Clostridium difficile infection with fecal microbiota transplantation[J].Clin Gastroenterol Hepatol,2011,9(12):1044-1049.
[29] Drekonja D,Reich J,Gezahegn S,et al. Fecal microbiota transplantation for clostridium difficile infection:a systematic review[J]. Ann Intern Med,2015,162(9):630-638.
[30]张成岗,巩文静,李志慧,等.医学3. 0与健康管理2. 0将促进健康中国战略的早日实现[J].转化医学电子杂志,2018,5(12):108-111.
[31]孔芳,洪康进,徐航,等.基于啮食泡沫塑料黄粉虫肠道菌群中聚苯乙烯生物降解的探究[J].微生物学通报,2018,45(7):1438-1449.
[32] Yang J,Yang Y,Wu W M,et al. Evidence of polyethylene biodegradation by bacterial strains from the guts of plastic-eating waxworms[J]. Environ Sci Technol,2014,48(23):13776-13784.
[33] Lee K,Vuong H E,Nusbaum D J,et al. The gut microbiota mediates reward and sensory responses associated with regimen-selective morphine dependence[J]. Neuropsychopharmacology,2018,43(13):2606-2614.
[34]张成岗,巩文静,李志慧,等.菌心进化论:一种对于动物进化的新理解[J].生物信息学,2018,16(4):203-213.
[35]张成岗,巩文静,李志慧,等.基于对人体结构与功能的新认识将促进健康现代化[C].第十六期中国现代化研究论坛论文集,2018:71-77.
[36] Fetissov S O. Role of the gut microbiota in host appetite control:bacterial growth to animal feeding behaviour[J]. Nature reviews Endocrinology,2017,13(1):11-25.
[37] Carter M E,Soden M E,Zweifel L S,et al. Genetic identification of a neural circuit that suppresses appetite[J]. Nature,2016,503(7474):111-114.
[38] Atasoy D,Betley J N,Su H H,et al. Deconstruction of a neural circuit for hunger[J]. Nature,2012,488(7410):172-177.
[39] Hameed S,Dhillo W S,Bloom S R. Gut hormones and appetite control[J]. Gastroenterology,2009,132(6):2116-2130.
[40]巩文静,张岩,郭素霞,等.医院体检中心基于柔性辟谷技术进行全链条闭环式体质量管理工作模式的初步研究[J].实用临床医药杂志,2019,23(5):7-10,15.
[41] Janssen S,Depoortere I. Nutrient sensing in the gut:new roads to therapeutics[J]. Trends in Endocrinology&Metabolism Tem,2013,24(2):92-100.