微生物-肠-脑轴的研究进展

肠道微生物群能够调节宿主肠道稳态,同时参与调节宿主神经系统功能和行为。肠道菌群失调可能导致宿主神经系统功能障碍,从而引发神经退行性疾病。因此,研究微生物在肠?脑轴中发挥的作用及其机制,靶向调控肠道微生物菌群结构和功能,将为神经系统疾病的诊断与治疗提供新的手段。近年来,有关肠道微生物与机体神经系统间的互作研究受到了广泛关注,然而其具体的调控机制还未明晰。因此,本文综述了肠道微生物对宿主神经健康的调节作用,以及肠道微生物与宿主间的互作在调节神经功能、行为的潜力等研究进展,为更好地了解肠道微生物在调控宿主神经系统功能和行为的作用机制提供参考。     

The role of gut microbiota in the gut-brain axis: current challenges and perspectives

Brain and the gastrointestinal (GI) tract are intimately connected to form a bidirectional neurohumoral communication system. The communication between gut and brain, knows as the gut-brain axis, is so well established that the functional status of gut is always related to the condition of brain. The researches on the gut-brain axis were traditionally focused on the psychological status affecting the function of the GI tract. However, recent evidences showed that gut microbiota communicates with the brain via the gut-brain axis to modulate brain development and behavioral phenotypes. These recent fi ndings on the new role of gut microbiota in the gut-brain axis implicate that gut microbiota could associate with brain functions as well as neurological diseases via the gut-brain axis. To elucidate the role of gut microbiota in the gut-brain axis, precise identification of the composition of microbes constituting gut microbiota is an essential step. However, identifi cation of microbes constituting gut microbiota has been the main technological challenge currently due to massive amount of intestinal microbes and the diffi culties in culture of gut microbes. Current methods for identifi cation of microbes constituting gut microbiota are dependent on omics analysis methods by using advanced high tech equipment. Here, we review the association of gut microbiota with the gut-brain axis, including the pros and cons of the current high throughput methods for identifi cation of microbes constituting gut microbiota to elucidate the role of gut microbiota in the gut-brain axis.     

Shift in brain metabolism in late onset Alzheimer's disease: implications for biomarkers and therapeutic interventions

Alzheimer's is a neurodegenerative disease with a complex and progressive pathological phenotype characterized first by hypometabolism and impaired mitochondrial bioenergetics followed by pathological burden. Increasing evidence indicates an antecedent and potentially causal role of mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress in AD pathogenesis. Compromised mitochondrial bioenergetics lead to over-production of and mitochondrial accumulation of β-amyloid, which is coupled with oxidative stress. Collectively, this results in a shift in brain metabolic profile from glucose-driven bioenergetics towards a compensatory, but less efficient, ketogenic pathway. We propose that the compensatory shift from a primarily aerobic glycolysis pathway to a ketogenic/fatty acid β-oxidation pathway eventually leads to white matter degeneration. The essential role of mitochondrial bioenergetics and the unique trajectory of compensatory metabolic adaptations in brain enable a bioenergetic-centric strategy for development of biomarkers. From a therapeutic perspective, this trajectory of alterations in brain metabolic capacity enables disease-stage specific strategies to target brain metabolism for disease prevention and treatment. A combination of nutraceutical and pharmaceutical interventions that enhance glucose-driven metabolic activity and potentiate mitochondrial bioenergetic function could prevent the antecedent decline in brain glucose metabolism, promote healthy aging and prevent AD. Alternatively, during the prodromal incipient phase of AD, sustained activation of ketogenic metabolic pathways coupled with supplementation of the alternative fuel source, ketone bodies, could sustain mitochondrial bioenergetic function to prevent or delay further progression of the disease.     

肠道菌群-肠-脑-肌轴信号交流的研究进展

肠道菌群及其代谢产物在老年神经退行性疾病、胃肠道疾病以及肌肉骨骼系统性疾病的发病与康复中的作用越来越受到关注。肠道菌群及其代谢产物可通过免疫、内分泌和神经系统等多种途径调节大脑神经或肌肉骨骼系统功能;反之,肠道、大脑或肌肉骨骼系统也可通过炎症、代谢或线粒体通路作用于肠道系统,调节肠道菌群微生态,形成肠道菌群与肠-脑、肠-肌、 肠-脑-肌之间的双向信号交流机制,从而影响机体健康。因此,本综述总结了肠道菌群如何通过代谢产物、肠道通透性和免疫-神经通路建立起肠-脑-肌之间的相互联系,为促进大脑神经的可塑性和改善肌肉健康提供新思路。     

肠道菌群与大脑相互作用的研究进展

定植于宿主肠道中的微生物参与了宿主多种生理功能以及相关疾病的发生。一个新的医学研究热点在近年内逐渐被关注,肠道菌群可通过主要由神经—内分泌介导的肠—脑轴(gut-brain axis,GBA)与大脑进行双向式交流。GBA不仅实现了肠道菌群对大脑发育和功能的影响,也促使大脑对肠道菌群结构和多样性的改变成为可能。本文旨在对肠道菌群与大脑相互作用的研究进展作一综述,以期为肠道和大脑功能领域的研究以及重要相关疾病的治疗策略提供理论依据。     

Comparative analysis of the gut microbiota composition in the Cln1R151X and Cln2R207X mouse models of Batten disease and in three wild-type mouse strains

Archives of Microbiology - Accumulated evidence indicates that the gut microbiota affects brain function and may be altered in neurological diseases. In this study, we analyzed the gut microbiota...     

肠道微生物与血清素互作研究进展

肠道微生物在肠道稳态和大脑健康中发挥着举足轻重的作用.血清素是大脑的一种重要的单胺类神经递质,90％以上在结肠肠嗜铬细胞中由色氨酸代谢转化而来,在机体发挥广泛作用.近年来的研究表明,血清素对机体发挥的作用可能受到肠道微生物影响.肠道中某些微生物具有产生血清素的能力,同时,微生物群及其代谢产物(如丁酸)能通过影响色氨酸羟...     

肠道微生物与线粒体之间的互作

肠道微生物与肠道细胞线粒体功能之间的关系十分密切。一方面,肠道微生物可直接或通过短链脂肪酸、硫化氢和一氧化氮等代谢产物间接影响与线粒体相关的能量代谢过程,调节线粒体活性氧的产生,调控线粒体甚至整个机体的免疫反应。另一方面,肠道细胞线粒体功能紊乱和基因组的遗传变异也会影响肠道微生物的组成和功能。本文主要介绍了肠道微生物和线粒体之间的互作关系的最新研究进展,为靶向作用于肠道菌群和线粒体以调节肠道健康提供理论依据。     

Mitochondria could be a potential key mediator linking the intestinal microbiota to depression

The intestinal microbiota has been reported to affect depression, a common mental condition with severe health-related consequences. However, what mediates the effect of the intestinal microbiota on depression has not been well elucidated. We summarize the roles of the mitochondria in eliciting beneficial effects on the gut microbiota to ameliorate symptoms of depression. It is well known that mitochondria play a key role in depression. An important pathogenic factor, namely inflammatory response, may adversely impact mitochondrial functionality to maintain cellular homeostasis. Dysfunction of mitochondria not only affects neuronal function but also reduces neuron cell numbers. We posit that the intestinal microbiota could affect neuronal mitochondrial function through short-chain fatty acids such as butyrate. Brain inflammatory processes could also be affected through the modulation of gut permeability and blood lipopolysaccharide levels. Aberrant mitochondria functionality coupled to adverse cellular homeostasis could be a key mediator for the effect of the intestinal microbiota on the progression of depression.     

肠道微生物菌群对脑及行为的影响

肠道微生物菌群组成的变化对正常生理的影响及其在疾病中的作用逐渐成为研究热点。肠道微生物菌群通过脑肠轴影响宿主生理学的各个方面,包括脑-肠交流、脑功能甚至行为。对无菌动物、被致病细菌感染的、使用益生菌或用抗生素药物的动物研究表明,肠道微生物菌群可以调节宿主焦虑样症状及行为。研究表明对肠道微生物菌群的调节可能是治疗复杂中枢神经系统失调症的新策略。     

肠道微生物群在人类健康衰老中的作用机制研究进展北大核心

衰老的特征是组织器官的功能衰退以及衰老相关疾病风险的增加,这给维护和促进健康长寿带来一系列新的挑战。尽管进行了广泛的衰老相关研究,但进展有限。人们越来越意识到肠道微生物群的结构和功能积极参与了衰老过程。肠道微生物群紊乱表现为许多与年龄相关的肠外器官轴的衰老。肠道微生物群可以被调节,这暗示了通过肠道微生物群抗衰老是一个可以实现的重要目标。本综述总结了肠道微生物群在不同年龄段中的动态演替,这种动态的肠道微生物群从胎儿到出生和婴儿期开始迅速发展,从断奶期到幼儿期迅速变化,然后建立稳定的成年人菌群,直到随着年龄增长最后发生衰退;肠道微生物群与肠外器官轴(大脑、心脏、肝脏、胰腺、肌肉、皮肤和骨骼)衰老相关疾病,以及通过饮食、粪菌移植和微生态制剂调节肠道微生物群靶向抗衰老的研究进展,以期为调控肠道微生物群抗衰老研究提供参考。     

Microbes and the mind: emerging hallmarks of the gut microbiota–brain axis

The concept of a gut microbiota–brain axis has emerged to describe the complex and continuous signalling between the gut microbiota and host nervous system. This review examines key microbial‐derived neuromodulators and structural components that comprise the gut microbiota–brain axis. To conclude, we briefly identify current challenges in gut microbiota–brain research and suggest a framework to characterize these interactions. Here, we propose five emerging hallmarks of the gut microbiota–brain axis: (i) Indistinguishability, (ii) Emergence, (iii) Bidirectional Signalling, (iv) Critical Window Fluidity and (5) Neural Homeostasis.     

Microbiota-gut-brain axis in autism spectrum disorder

Extensive studies, largely during the past decade, identify the dynamic and bidirectional interaction between the bacteria resident in the intestines and their host brain along the "microbiota-gut-brain axis". This interaction modulates the development and function of the central nervous system and is implicated in neurological disorders. As a neurodevelopmental disorder, autism spectrum disorder (ASD) is considered a historically defect in the brain. With accumulating evidence showing how the microorganisms modulate neural activities, more and more research is focusing on the role of the gut microbiota in mitigating ASD symptoms and the underlying mechanisms. In this review, we describe the intricate and crucial pathways via which the gut microbiota communicates with the brain, the microbiota-gut-brain axis, and summarize the specific pathways that mediate the crosstalk of the gut microbiota to the brain in ASD.     

The Gut Microbiota–Brain Axis Expands Neurologic Function: A Nervous Rapport

Does exploration of the gut microbiota–brain axis expand our understanding of what it means to be human? Recognition and conceptualization of a gut microbiota–brain axis challenges our study of the nervous system. Here, integrating gut microbiota–brain research into the metaorganism model is proposed. The metaorganism—an expanded, dynamic unit comprising the host and commensal organisms—asserts a radical blurring between man and microbe. The metaorganism nervous system interacts with the exterior world through microbial‐colored lenses. Ongoing studies have reported that gut microbes contribute to brain function and pathologies, even shaping higher neurological functions. How will continued collaborative efforts (e.g., between neurobiology and microbiology), including partnerships with the arts (e.g., philosophy), contribute to the knowledge of microbe‐to‐mind interactions? While this is not a systemic review, this nascent field is briefly described, highlighting ongoing challenges and recommendations for emerging gut microbiota–brain research. Also see the video abstract here https://youtu.be/lP9gOW8StXg .     

Exploring the gut microbiota composition of Indian major carp,rohu (Labeo rohita), under diverse culture conditions

Gut microbiota of freshwater carps are often investigated for their roles in nutrient absorption, enzyme activities and probiotic properties. However, little is known about core microbiota, assembly pattern and the environmental influence on the gut microbiota of the Indian major carp, rohu. The gut microbial composition of rohu reared in different culture conditions was analysed by 16S rRNA amplicon sequencing. There was variation on gut microbial diversity and composition. A significant negative correlation between dissolved oxygen content (DO) and alpha diversity was observed, thus signifying DO content as one of the key environmental factors that regulated the diversity of rohu gut microbial community. A significant positive correlation was observed between phosphate concentration and abundance of Actinobacteria in different culture conditions. Two phyla, Proteobacteria and Actinobacteria along with OTU750868 (Streptomyces) showed significant (p < 0.05) differences in their abundance among all culture conditions. The Non-metric multidimensional scaling ordination (NMDS) analysis using Bray-Curtis distances, showed the presence of unique gut microbiota in rohu compared to other herbivorous fish. Based on niche breadth, 3 OTUs were identified as core generalists, persistent across all the culture conditions whereas the specialists dominated in the rohu gut microbiota assembly. Co-occurrence network analysis revealed positive interaction within core members while mutual exclusion between core and non-core members. Predicted microbiota function revealed that different culture conditions affected the metabolic capacity of gut microbiota of rohu. The results overall indicated the significant effect of different rearing environments on gut microbiota structure, assembly and inferred community function of rohu which might be useful for effective manipulation of gut microbial communities of rohu to promote better health and growth under different husbandry settings.     

"肠道微生物-肠道-脑轴"机制--肠道微生物干预神经退行性病变研究进展

肠道微生物是人体中最为庞大和复杂的微生物群落,其对机体的健康,尤其是中枢神经退行性病变具有重要调节作用。其中,"肠道微生物-肠道-脑轴"机制是肠道微生物干预中枢神经退行性病变的重要途径。该机制主要通过以下三种方式来调节大脑功能:一是肠道微生物直接产生神经递质通过肠神经细胞上行至中枢神经系统;二是肠道微生物代谢产物刺激肠内分泌细胞产生神经肽类和胃肠激素类物质,影响大脑功能;三是肠道微生物或其代谢产物直接刺激肠道免疫系统,产生干扰素类物质干扰大脑免疫反应。本文对"肠道微生物-肠道-脑轴"机制的概念及研究进展进行了详细的介绍,同时总结了有关肠道微生物与阿尔兹海默症、帕金森症和多发性硬化症等神经退行性疾病相互作用的相关文献。依据"肠道微生物-肠道-脑轴"机制,利用肠道微生物预防和治疗神经退行性病变,或将成为解决中枢神经系统疾病的新措施。     

Beneficial modulation of the gut microbiota

The human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.     

Nutritional modulation of the intestinal microbiota; future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease

The gut–brain axis refers to the bidirectional communication between the enteric nervous system and the central nervous system. Mounting evidence supports the premise that the intestinal microbiota plays a pivotal role in its function and has led to the more common and perhaps more accurate term gut–microbiota–brain axis. Numerous studies have identified associations between an altered microbiome and neuroimmune and neuroinflammatory diseases. In most cases, it is unknown if these associations are cause or effect; notwithstanding, maintaining or restoring homeostasis of the microbiota may represent future opportunities when treating or preventing these diseases. In recent years, several studies have identified the diet as a primary contributing factor in shaping the composition of the gut microbiota and, in turn, the mucosal and systemic immune systems. In this review, we will discuss the potential opportunities and challenges with respect to modifying and shaping the microbiota through diet and nutrition in order to treat or prevent neuroimmune and neuroinflammatory disease.     

人体肠道菌群来源碳水化合物活性酶（CAZYmes） 研究进展

肠道菌群是人体重要的代谢"器官",对人体的健康和疾病起着至关重要的作用.肠道菌群参与人体消化、免疫、神经系统调节机能的分子机理是特异性物质代谢通路在微生物与人体之间的协同耦合.酶是代谢通路中参与物质转化的基本功能单元,深入理解肠道菌群编码酶的分子催化机理将为以肠道菌群(或肠道酶)作为靶点的精准营养/医疗干预研究提供重要理论依据.特异性底物酶解研究表明,肠道菌群编码的酶系统不仅包含全部已知的碳水化合物活性酶(carbohydrateactive enzymes, CAZYmes)类,同时蕴含诸多潜在的新型CAZYmes.本文阐述CAZYmes的分类原则及催化机理,并主要从结构生物学方面综述人体肠道菌群来源的新型CAZYmes.     

Alzheimer’s disease and gut microbiota

Alzheimer’s disease (AD) is a most common neurodegenerative disorder, which associates with impaired cognition. Gut microbiota can modulate host brain function and behavior via microbiota-gut-brain axis, including cognitive behavior. Germ-free animals, antibiotics, probiotics intervention and diet can induce alterations of gut microbiota and gut physiology and also host cognitive behavior, increasing or decreasing risks of AD. The increased permeability of intestine and blood-brain barrier induced by gut microbiota disturbance will increase the incidence of neurodegeneration disorders. Gut microbial metabolites and their effects on host neurochemical changes may increase or decrease the risk of AD. Pathogenic microbes infection will also increase the risk of AD, and meanwhile, the onset of AD support the “hygiene hypothesis”. All the results suggest that AD may begin in the gut, and is closely related to the imbalance of gut microbiota. Modulation of gut microbiota through personalized diet or beneficial microbiota intervention will probably become a new treatment for AD.