肠道微生物体外模型研究进展

随着分子微生态学,特别是高通量测序技术的发展,人类对肠道微生物的作用有了新的突破性认识。我们现在了解到人体和动物消化道系统中生长着大量的细菌,肠道中细菌的总数量甚至高出人体细胞总数的十倍。肠道微生物的菌群多样性受到多种因素的影响。其中环境和宿主的遗传背景在决定肠道菌群结构和组成方面各自起到50％的作用。     

动物及其肠道菌群的协同进化研究

动物自身合成一些关键营养物质的能力缺失,转而依赖体内的共生物来完成相应功能,如动物体内共生细菌能帮助宿主从食物中提取营养物质,并能合成一些关键代谢反应的化合物。结合国内外在动物及其肠道菌群的协同进化的研究进展,从三个方面进行了归纳:(1)动物及其肠道微生物组成与功能的协同进化研究;(2)动物行为与肠道微生物的关系;(3)共生肠道微生物在人类或动物自身消化食物、营养获取、健康和疾病方面发挥的重要作用。     

在达尔文以前地球如何从无生命进入生命形式

正如官方说法和法庭争论可以看出公众对于达尔文进化论解释人类起源存在争论一样,科学界就关于进化论作为生物学的理论基础是否足够的问题展开了不同的争论。表面上看来,这两种争论之间没什么联系,但是都微妙反应了对于一种更丰富的理论生物学的渴求。通过对有关进化论局限性的学术考虑以及这些考虑如何被提出的进行更好沟通,能够有效促进广大公众对进化概念的理解。     

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

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。     

肠道菌群功能与影响因素研究进展

人体肠道作为一种营养丰富的天然环境有多达100兆个微生物,其中绝大多数存于结肠内,密度接近1011~1012/m L。人类肠道内的微生物多样性是微生物菌落和宿主共同进化的结果,自然选择和进化使肠道菌群与宿主处于一种动态平衡且稳定的关系。文章综述了肠道菌群对宿主可能产生的影响以及引起肠道菌群发生改变的某些因素,肠道微生物影响宿主的代谢、营养吸收、免疫功能以及神经功能调节,而饮食及其他条件又能引起肠道菌群的改变。深入分析肠道菌群的具体结构、探索不同微生物在宿主体内究竟发挥着怎样的作用以及如何充分利用微生物的不同特性改善人类健康应成为今后研究的重点方向。     

进化猜想

达尔文在进化论中首次提出了人类是由猿进化而来的假说。自此以后,这个结论一直有不少科学家在争论。其中一个很重要的疑问是:猿猴的体毛很密很长,而人类的体毛为什么十分稀疏?为此,不少科学家又提出了一些十分奇特的猜想,其中比较重要     

肠道菌群代谢产物在鼠伤寒沙门菌感染中的作用研究进展

人和动物肠道内生存着多种多样的微生物群体,它们与宿主共同进化,对宿主的健康至关重要。肠道菌群可以发酵宿主难以消化的复杂碳水化合物,为宿主肠道细胞提供能量,同时其代谢产物对肠道病原菌沙门菌的感染产生着重要影响。正常情况下,肠道菌群代谢产物如丁酸与丙酸可以抑制沙门菌在肠道中的定植或者毒力基因的表达,而在肠道菌群受到扰乱时,其代谢的琥珀酸盐和1,2-丙二醇等物质却能促进沙门菌增殖。近年来,越来越多的研究揭示了肠道菌群代谢产物对沙门菌感染的影响。本综述通过总结近年来关于鼠伤寒沙门菌入侵时肠道菌群代谢产物改变的研究,综合阐述了肠道菌群代谢产物影响沙门菌感染的机制。     

肠道菌群与代谢研究进展

从出生伊始肠道菌群就依赖于宿主的基因组、营养和生活方式而变化的,与宿主共同进化发展.肠道菌群参与调控其宿主的多种代谢途径,包括宿主的免疫、营养,并且极大地影响宿主的物质能量代谢及与物质能量代谢相关疾病的发生与发展过程.同时又与多个器官共同作用,在宿主的代谢、信息传递,疾病的感染与防御方面起非常重要的作用.深入了解肠道菌群在其参与代谢的具体作用,对理解物质能量代谢相关疾病病因、优化治疗策略、调节肠道菌群、防治疾病和提高宿主健康水平具有重要作用.本研究对人类肠道菌群的形成、物质能量代谢、代谢相关疾病及其防治等方面的研究进展加以综述.     

是谁创造了人类的鼻子

无论是从古生物学还是现代动物的比较研究都不难证实,只有我们这些自称为“有理性”的人类才在扁平的脸面上长着这么个高挺的鼻子,具有挺起的鼻梁和前突的鼻头,鼻孔朝下。人类的祖先——类人猿和其现代近亲猿猴类没有这样的鼻子,大多数现代猿猴只是在扁平的脸上露出两个朝前的鼻孔。其它所有具有类似高挺或前突鼻子的动物其脸面也必然会相应的前突,而不象人的鼻子那样犹如一马平川上突然隆起的一个小山丘。人为什么会长出这么个高挺的鼻子呢?鼻子是随着人脱离动物界变成有理性的人而出现的,它是如何进化的?其起源包含有什么特殊的含义     

肠道菌群与肿瘤的相关性

人类肠道中有500余种细菌,参与消化、代谢和免疫等生理活动。肠道菌群因其数量庞大、作用显著,被称为人体的"第二基因"。随着研究的不断深入,发现肠道菌群与多种疾病如心脑血管疾病、糖尿病、肥胖、胃肠炎甚至肿瘤的发生息息相关。恶性肿瘤作为一种病死率极高的疾病,近年来与其相关的研究也越来越丰富。研究者们发现,肠道菌群在肺癌、黑色素瘤、消化道肿瘤和血液系统肿瘤等的发生、发展及治疗中发挥着重要的作用,已成为近年来的研究热点。因此,本文对肠道菌群与各类肿瘤的关系研究进展进行综述。     

Studies on the bacterial flora of tubificid worms

Study of the bacterial flora of the gut of the turbificid worms has shown that u. v. starilization, serial culturing, and standard bacterial identification procedures can be employed successfully. Eighteen species of bacteria were isolated and identified from the gut of tubificid worms. Eleven of the species were Gram negative which may be reflected in their possible association with chlorogonal cell metabolism in tubificid worms. Of the eighteen species identified our genera and two species are on a similar list produced by Brinkhurst & Chua in an earlier study (1969) of worms from the Great Lakes. None of the organisms identified were other than common to fresh water, organic decay processes or animal digestive systems. Their role in tubificid nutrition is now under study.Supported by a grant from the Council on Faculty Research, Eastern Illinois University.     

Feedback selection and the evolution of modifiers

The problem of modifier evolution was examined with regard to the idea that modifier evolution can be considered as a result of selection for adaptation speed in populations far from equilibrium. This kind of selection was called feedback selection in order to emphasize the difference to theories which consider modifier evolution near the equilibrium. The basic principles of this kind of selection are derived for asexual populations and the problem of dominance is discussed in the light of this concept. In general the results support the view, that the genetic properties of a character are selected along with the character itself.This work was supported by the Austrian Fonds zur Förderung der Wissenschaftlichen Forschung (Proj. Nr. 3502).     

Multiple isolations of a culturable, motile Ichthyosporean (Mesomycetozoa, Opisthokonta), Creolimax fragrantissima n. gen., n. sp., from marine invertebrate digestive tracts

A fragrant, spherical, osmotrophic eukaryote was isolated 27 times from the digestive tracts of marine invertebrates collected from the Northeast Pacific. The isolates were cultured from 7 animal collections over a 2-year period, most from the peanut worm, Phascolosoma agassizii. A small subunit ribosomal DNA phylogeny placed the spherical organism within the ichthyosporea, closest to Sphaeroforma arctica and Pseudoperkinsus tapetis. Supporting the close relationship of isolates, the sequences of ribosomal gene internal transcribed spacers determined for 26 isolates were identical, as were the elongation factor 1-alpha-like gene fragments from 7 isolates. Dispersal via amoeboid cells distinguished this species from its closest relatives and led to the erection of a new genus and species, "Creolimax fragrantissima." Vegetative cells reproduced asexually in vitro after they reached 30-60 microm in diameter by producing amoebae or endospores, which escaped through openings in the parent cell wall. Ultrathin sections of vegetative cells prepared by high-pressure-freeze substitution provided some of the first images of ichthyosporean spindle pole bodies and document, for the first time, tubular extensions of the plasma membrane into an electron-translucent inner layer of the cell wall. Ichthyosporeans are parasites and commensals of animals and culturable species are few. Because "C. fragrantissima" can be isolated regularly and repeatedly from nature and then grown easily through cycles of asexual reproduction, it has the potential to serve as a model organism for further research into marine ichthyosporeans.     

The evolution of aggressive losers

We examine the question of when aggressive behavior of likely losers should be part of an evolutionarily stable strategy. We modified an earlier model by the authors that found situations where likely losers initiate aggressive interactions more often than likely winners. The modifications allowed us to examine the robustness of the previous study by including an unusually high number of possible strategies (n=81) and to examine a wide range of parameter settings. First, we show that restricting attention to only a few most plausible strategies may change the overall results. Second, within the space where escalation is predicted, for a large percentage of the parameter settings (85%), an ESS exists that leads to a somewhat counterintuitive situation where escalation is more often initiated by the likely loser than by the likely winner of the contest. In contrast, an ESS that favors escalation by likely winners was found only for about 3% of parameter settings. Furthermore, we use simulations of evolution in a finite population to verify for certain parameter settings that the analytically predicted ESS's could in fact evolve. Our results suggest that ESSs in which the likely loser rather than the likely winner is expected to initiate escalation are generic and ESSs in which the opposite is true need to be explained by incorporating specific features of the biology of a given species into more detailed models.     

A mathematical model of biological evolution

In order to understand generally how the biological evolution rate depends on relevant parameters such as mutation rate, intensity of selection pressure and its persistence time, the following mathematical model is proposed: dN _n (t)/dt=(m _n (t-)N _n (t)+N _n-1(t) (n=0,1,2,3...), where N _n (t) and m _n (t) are respectively the number and Malthusian parameter of replicons with step number n in a population at time t and is the mutation rate, assumed to be a positive constant. The step number of each replicon is defined as either equal to or larger by one than that of its parent, the latter case occurring when and only when mutation has taken place. The average evolution rate defined by is rigorously obtained for the case (i) m _n (t)=m _n is independent of t (constant fitness model), where m _n is essentially periodic with respect to n, and for the case (ii) (periodic fitness model), together with the long time average m of the average Malthusian parameter . The biological meaning of the results is discussed, comparing them with the features of actual molecular evolution and with some results of computer simulation of the model for finite populations.An early version of this study was read at the International Symposium on Mathematical Topics in Biological held in kyoto, Japan, on September 11–12, 1978, and was published in its Procedings.     

枯草杆菌二联活菌肠溶胶囊对 溃疡性结肠炎患者肠道菌群的影响

目的探讨枯草杆菌二联活菌肠溶胶囊对溃疡性结肠炎患者肠道菌群的影响。方法选取2017年4月至2017年9月同济大学附属第十人民医院消化内科门诊收治的10例溃疡性结肠炎患者为研究对象。患者均在美沙拉嗪治疗基础上加用枯草杆菌二联活菌肠溶胶囊治疗1个月,留取治疗前后新鲜粪便样本,并采用16SrRNA细菌检测技术鉴定肠道菌群。结果患者经过治疗后其肠道菌群的丰富度没有发生改变,菌群的多样性增高。在门水平上,厚壁菌门丰度增高,而变形菌门的丰度下降。在属水平上,Actinobacillus和Escherichia/Shigella的丰度下降,Veillonella、Clostridium XIVa、Blautia、Proteus、Flavonifractor等的丰度增高(P0.05)。通过Lefse分析发现c_Gammaproteobacteria和p_Firmicutes是患者治疗前后的特征性菌群。结论枯草杆菌二联活菌肠溶胶囊可以改善溃疡性结肠炎患者的肠道菌群失调,在常规治疗中添加益生菌可成为一种新的治疗策略。     

食物氧化蛋白对小鼠肠道菌群及氧化还原状态的影响

目的研究摄食不同方式氧化酪蛋白对小鼠肠道菌群和氧化还原状态的影响。方法分别以H2O2/Cu2+、HClO处理酪蛋白,丙二醛(MDA)处理酪蛋白、大豆蛋白。雄性KM小鼠分为6组:酪蛋白组,H2O2-Cu2+氧化酪蛋白组,HClO氧化酪蛋白组,MDA氧化酪蛋白组,大豆蛋白组和MDA氧化大豆蛋白组,饲喂10周。结果酪蛋白和大豆蛋白经氧化处理后羰基含量显著上升(P0.05),体外消化率下降。饲喂氧化蛋白饲粮的小鼠结肠内容物乳杆菌数量均显著低于对照组(P0.05);HClO和MDA氧化酪蛋白组大肠埃希菌、肠球菌数量显著高于对照组(P0.05),MDA氧化大豆蛋白组大肠埃希菌数量显著高于对照组(P0.05)。氧化蛋白处理引起小鼠结肠组织MDA上升,其中MDA氧化蛋白处理达显著水平(P0.05);结肠过氧化氢酶(CAT)活力上升,其中H2O2/Cu2+和MDA氧化蛋白组达显著水平(P0.05);H2O2/Cu2+氧化酪蛋白处理引起结肠GSH-Px显著升高(P0.05);氧化蛋白引起结肠总抗氧化能力(T-AOC)下降,其中H2O2/Cu2+、HClO氧化酪蛋白和MDA氧化大豆蛋白处理达显著水平(P0.05)。蛋白质体外消化率与结肠肠球菌呈负相关(R=-0.81,P=0.051);蛋白羰基含量与结肠乳杆菌呈显著负相关(R=-0.94,P0.01);大肠埃希菌(R=0.93,P0.01)和肠球菌(R=0.85,P0.05)分别与蛋白羰基含量呈正相关。结论氧化后蛋白消化率降低、羰基含量增高,导致肠道乳杆菌减少,大肠埃希菌和肠球菌上升;结肠黏膜脂质过氧化,氧化损伤程度与蛋白氧化处理方式有关。     

Isolation of facultatively aerobic actinomycetes from the gut, parent soil and mound materials of the termites Procubitermesaburiensis and Cubitermes severus

Abstract Isolates of the genus Streptomyces were readily obtained from the intestines of two African species of soil-feeding termites by an aerobic explant technique using starch casein medium, and from their parent soil and mound materials by dilution plating. Discriminant analysis of the isolates, based on 44 representative characters, showed that the population derived directly from the termites was significantly different from that of the feed soil or the mound. The termite gut was considered to be a good source of unusual actinomycetes, but strains isolated under aerobic conditions are likely to be allochthons selected by the intestinal environment, which is highly alkaline and anaerobic. An anaerobic, filamentous isolate was obtained which may be a component of the prokaryotic symbiont population mediating termite digestion.     

The evolution of cultural evolution

Humans are unique in their range of environments and in the nature and diversity of their behavioral adaptations. While a variety of local genetic adaptations exist within our species, it seems certain that the same basic genetic endowment produces arctic foraging, tropical horticulture, and desert pastoralism, a constellation that represents a greater range of subsistence behavior than the rest of the Primate Order combined. The behavioral adaptations that explain the immense success of our species are cultural in the sense that they are transmitted among individuals by social learning and have accumulated over generations. Understanding how and when such culturally evolved adaptations arise requires understanding of both the evolution of the psychological mechanisms that underlie human social learning and the evolutionary (population) dynamics of cultural systems.