肠道菌群对机体营养物质的代谢研究

<正>人体肠道内寄居的微生物种类繁多,主要以厌氧菌为主,而且数量巨大,约为人体细胞总和的10倍~([1])。正常的肠道菌群按一定的比例栖息于肠道内部,彼此之间互相制约,互相依存,共同维持人体肠道系统的平衡和稳定。人类机体通过摄食从外界获得的各种营养物质经过胃肠道的消化、吸收供给机体各种生命活动,而那些未消化、吸收的营养物质进入结肠后,将主要通过结肠内厌氧菌对其进行发酵,产生各种代谢产物~([2])。这些代谢产物对维持肠道     

肠道菌群-FXR轴在代谢性疾病中的作用

<正>肠道菌群是指在肠道定植的包括细菌、真菌、病毒、古细菌和原生动物在内的微生物群,其种类超过1 000种,数量接近人体自身细胞的10倍,编码基因数量超过人体自身基因100倍。肠道菌群按系统发育地位可分为厚壁菌门、拟杆菌门、变形菌门、放线菌门、疣微菌门和梭杆菌门。正常人类肠道菌群主要由厚壁菌门和拟杆菌门组成~([1])。近年来科学界对肠道微生物群产生了浓厚的兴趣,肠道菌群与大量疾病如炎症性肠病、肠易激惹综合征、过敏性疾病和代谢性疾病有关。胆汁酸     

肠道菌群与抗肿瘤治疗

<正>人体肠道微生物菌群大约重1 000 g,种类大约30个属,300~500多种。细菌数量达到了1014个,是人体细胞总数的10倍。肠道菌群主要由厌氧菌、兼性厌氧菌和需氧菌组成,其中专性厌氧菌占99%以上。被认为是人类的"第二基因组"~([1])。肠道菌群的生物学功能可以从三方面来阐述:即维持肠道的正常结构和生理功能,拮抗病原微生物的定植、感染和刺激,调控人体的免疫功能。这些功能相互     

食物中的益生菌

<正>据Derrien M 2015年6月1日[Trends Microbiol,2015,23(6):354-366.]报道,来自食物的菌群确实影响着肠道微生物群和宿主健康。从食物进入肠道的很多益生菌确实能够进入小肠,而且躲过了胃里的强酸环境,仍然顽强地或者并还有生理活性,可以完成一些分子的合成代谢。这些微生物占据着正常肠道微生物群体的一部分,并且可很多次在肠道微生物群的分析中被检测出来。肠道微生物群是存在于人体肠道的微生物群体的总称,其中包括了细菌、真菌、古菌及原生物动植物(甚至病毒)等种类众多     

肠道菌群及其在炎症性肠病中的作用

人体肠道内存在数量庞大、种类繁多的肠道细菌,这些细菌与人体环境保持平衡状态,共同参与人体的正常生理过程。它们在防御病原体入侵、维持人体免疫系统稳态以及物质代谢与生物转化等方面发挥独特作用。肠道菌群的稳态是维持健康的必要条件,而肠道菌群的失调与许多疾病如肥胖、糖尿病、结直肠癌、抑郁及炎症性肠病等的发生密切相关。多项研究发现,肠道菌群失调介导的免疫损伤是炎症性肠病(IBD)的重要发病机制,在IBD患者中针对肠道菌群紊乱的治疗方法取得了较好的效果。本文阐述了人体肠道菌群组成、肠道菌群的功能及肠道菌群与IBD关系的最新研究进展,为进一步的研究提供借鉴和帮助。     

无菌小鼠在肠道菌群研究中的应用概述

人类胃肠道中有10~100万亿微生物,这些微生物归属于9个细菌门,其中厚壁菌门和拟杆菌门微生物占了绝大多数^[1-3]。近年来,越来越多的研究证实,肠道菌群与肥胖相关疾病、心血管疾病、代谢性疾病、肝病、炎症性肠病和结直肠癌存在联系,并在调节胰岛素敏感性、脂肪储存和体重方面发挥关键作用^[4-8]。在人体中,与基因相比,肠道菌群更具可塑性,其组成随年龄和饮食等因素而变化,因此有可能通过调节肠道菌群的组成来预防和治疗疾病。总的来说,肠道菌群的研究对维护人类健康具有重要意义。     

肠道菌群与疾病相关性的研究进展

肠道菌群数量庞大、种类繁多,其与宿主相互依存、相互影响。人体许多疾病的发生发展以及病情的转归都与肠道菌群有密不可分的联系。肠道微生物通过调节糖、脂质以及氨基酸等物质的代谢影响代谢疾病的发生与发展;肠道菌群紊乱还可促进炎性肠病与某些肠道肿瘤,补充益生菌可有助于这类疾病的治疗;此外,肠道菌群还与神经精神系统、心血管系统、泌尿系统等其他系统的疾病有着千丝万缕的联系。因此研究肠道菌群与疾病的相关性对疾病的预防与治疗,维护人类健康具有重大意义。     

肠道菌群与艾滋病关系的研究进展

肠道内定植数量众多、种类丰富的肠道菌群,它们与宿主之间形成互利共生的关系,而肠道菌群微环境的平衡与宿主的健康密切相关。HIV感染破坏肠道微环境的平衡,引起肠道菌群改变,且艾滋病(AIDS)的疾病进程与肠道菌群的改变密切相关。肠道微生物中益生菌所占比例的下降会降低AIDS患者的肠道代谢功能和免疫功能,促使肠道致病菌的增殖及生长,加快AIDS疾病进程。AIDS患者的持续性免疫活化和炎症反应破坏肠道免疫黏膜屏障,提高肠道细菌移位的发生率和AIDS患者的死亡率。改善肠道微生态系统已成为AIDS治疗研究的重要方面,本文系统介绍了肠道菌群与AIDS之间关系的新进展。     

益生菌在肝脏疾病方面的应用

<正>各种动物和人类肠道中都存在着大量微生物,其总量远远超过宿主的体细胞和生殖细胞数量,这些定殖微生物被称为微生物菌群,另外,在同一宿主内,宿主的年龄、遗传背景、饮食情况和健康状况等多种因素会影响微生物菌群的组成~([1])。近年来,随着对肠-肝轴认识的逐步深入,肠道菌群在肝脏疾病发病过程中的作用备受关注~([2])。益生菌在维持肠道     

肠道菌群和"肠-肺"轴在脓毒症中的作用

肠道菌群是寄生在人体肠道内数量庞杂的微生物群。"肠-肺"轴是连接肠道和肺部的双向轴。肠道菌群和"肠-肺"轴参与了脓毒症的发生与发展。脓毒症发生时,肠黏膜屏障受损,肠道菌群失调,细菌移位,肺为最先发生损伤的器官,肺部感染也会导致肠道功能紊乱。     

生物钟与肠道微环境、肠道免疫系统之间关系的研究进展

生物钟可以通过影响真核生物体内基因转录、改变生物氧化还原状态等方式保证机体每天进行正常的生长代谢节律波动,人体内的生物钟还能够调控肠道免疫细胞的增殖、分化及分泌功能.生物钟紊乱时会降低机体肠道免疫系统的抗病能力进而引起局部肠道黏膜损害或部分肠道炎症的发生.由大量微生物菌群组成的肠道微环境参与机体肠道黏膜保护、能量传递及营养代谢等生理过程,微环境发生改变时也会引起肠道病理性炎症反应.昼夜节律性改变也会改变正常的肠道微生态环境,使益生菌群数量下降并激活条件致病菌,产生大量有害代谢物质引起肠道炎症反应.生物钟、肠道菌群、肠道免疫系统之间存在着一定关系,但是它们之间的联系目前并不明确.明确生物钟、肠道微环境、肠道免疫防御、炎症性肠道疾病之间关系,从而探讨肠道疾病可能的发病机制,为炎症性肠道疾病治疗途径提供新的思路治疗途径提供新的思路.     

Circadian clock genes as promising therapeutic targets for autoimmune diseases

Circadian rhythm is a natural, endogenous process whose physiological functions are controlled by a set of clock genes. Disturbance of the clock genes have detrimental effects on both innate and adaptive immunity, which significantly enhance pro-inflammatory responses and susceptibility to autoimmune diseases via strictly controlling the individual cellular components of the immune system that initiate and perpetuate the inflammation pathways. Autoimmune diseases, especially rheumatoid arthritis (RA), often exhibit substantial circadian oscillations, and circadian rhythm is involved in the onset and progression of autoimmune diseases. Mounting evidence indicate that the synthetic ligands of circadian clock genes have the property of reducing the susceptibility and clinical severity of subjects. This review supplies an overview of the roles of circadian clock genes in the pathology of autoimmune diseases, including BMAL1, CLOCK, PER, CRY, REV-ERBα, and ROR. Furthermore, summarized some circadian clock genes as candidate genes for autoimmune diseases and current advancement on therapy of autoimmune diseases with synthetic ligands of circadian clock genes. The existing body of knowledge demonstrates that circadian clock genes are inextricably linked to autoimmune diseases. Future research should pay attention to improve the quality of life of patients with autoimmune diseases and reduce the effects of drug preparation on the normal circadian rhythms.     

Circadian regulation of epithelial functions in the intestine

Many physiological functions exhibit a diurnal rhythmicity that is influenced by biological clocks and feeding rhythms. In this review, we discuss the growing evidence showing the important role of circadian rhythms in regulating intestinal mucosa. First, we introduce the molecular timing system and the interrelationship between the master biological clock in the suprachiasmatic nuclei of the brain and the peripheral intestinal clock and provide evidence that the intestinal clock is entrained with the external environment. Second, we review the circadian rhythmicity of enterocyte proliferation and the largely unknown regulatory mechanisms behind these rhythms. Finally, we focus on the circadian clock control of food processing that functions by regulating the expression of digestive enzymes and intestinal nutrient and salt transporters. The concepts to be discussed highlight the ability of the intestinal epithelium to utilize self‐sustained clock signals together with signals associated with changes in the cellular environment and to use endogenous temporal control of the gastrointestinal functions to meet varying physiological and pathophysiological demands. The fact that internal de‐synchronizations within the body, such as those that occur in shift workers or with changes in food intake behaviour, are often associated with malfunctions of the gastrointestinal tract indicates that more information about the connections between the circadian clock and intestinal mucosa/transporting enterocytes could provide clues for future therapies.     

CircadiOmic medicine and aging

The earth displays daily, seasonal and annual environmental cycles that have led to evolutionarily adapted ultradian, circadian and infradian rhythmicities in the entire biosphere. All biological organisms must adapt to these cycles that synchronize the function of their circadiome. The objective of this review is to discuss the latest knowledge regarding the role of circadiomics in health and aging. The biological timekeepers are responsive to the environmental cues at microsecond to seasonal time-scales and act with precision of a clock machinery. The robustness of these rhythms is essential to normal daily function of cells, tissues and organs. Mis-alignment of circadian rhythms makes the individual prone to aging, sleep disorders, cancer, diabetes, and neuro-degenerative diseases. Circadian and CircadiOmic medicine are emerging fields that leverage our in-depth understanding of health issues, that arise as a result of disturbances in circadian rhythms, towards establishing better therapeutic approaches in personalized medicine and for geroprotection.     

The importance of being rhythmic: Living in harmony with your body clocks

Circadian rhythms have developed in all light‐sensitive organisms, including humans, as a fundamental anticipatory mechanism that enables proactive adaptation to environmental changes. The circadian system is organized in a highly hierarchical manner, with clocks operative in most cells of the body ensuring the temporal coordination of physiological processes. Circadian misalignment, stemming from modern life style, draws increasing attention due to its tight association with the development of metabolic, cardiovascular, inflammatory and mental diseases as well as cancer. This review highlights recent findings emphasizing the role of the circadian system in the temporal orchestration of physiology, with a particular focus on implications of circadian misalignment in human pathologies.     

Association of intrinsic circadian period with morningness-eveningness, usual wake time, and circadian phase

The biological basis of preferences for morning or evening activity patterns ("early birds" and "night owls") has been hypothesized but has remained elusive. The authors reported that, compared with evening types, the circadian pacemaker of morning types was entrained to an earlier hour with respect to both clock time and wake time. The present study explores a chronobiological mechanism by which the biological clock of morning types may be set to an earlier hour. Intrinsic period, a fundamental property of the circadian system, was measured in a month-long inpatient study. A subset of participants also had their circadian phase assessed. Participants completed a morningness-eveningness questionnaire before study. Circadian period was correlated with morningness-eveningness, circadian phase, and wake time, demonstrating that a fundamental property of the circadian pacemaker is correlated with the behavioral trait of morningness-eveningness.     

The circadian gene mPer2 regulates the daily rhythm of IFN-gamma.

Circadian and daily rhythms regulate many aspects of physiology and behavior. Although a growing number of studies suggest that circadian disruptions may render organisms more susceptible to infection and cancer, the molecular links between the circadian system and the immune system are largely unknown. Here we report that mice carrying a loss-of-function mutation in the Per2 gene, a key component of the molecular circadian clock, lacked the physiologic daily rhythm of interferon-gamma (IFN-gamma) mRNA and protein expression in the spleen. These observations were associated with a significant alteration in the expression of canonical clock genes. In addition, Per2 mutant mice failed to show a daily rhythm in IFN-gamma serum levels, which were significantly lower than those determined in wild-type mice during the early light period. These findings provide novel evidence for a direct circadian regulation of IFN-gamma, a critical cytokine modulating the immune response.