鬼臼毒素药源植物及其资源

鬼臼毒素属于木脂素类化合物中的芳基萘类,是一类重要的、具有一定的抗肿瘤和抗病毒活性的天然产物,能够产生鬼臼毒素类化合物的植物受到各国学者的关注。本文对近年来这类植物的形态、生境、化学成分及其内生菌代谢产物的研究进行了回顾。     

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。     

人体肠道4 644株代表菌次级代谢产物生物合成基因簇挖掘与耐药及毒力基因分析

为了更好地从肠道微生物组中挖掘新的次级代谢产物、了解肠道微生物组编码的抗生素耐药基因和毒力因子情况,本研究基于4 644株人体肠道微生物代表菌的基因组序列,对其编码的次级代谢产物基因簇、抗生素耐药基因和毒力因子进行了预测分析。经antiSMASH预测分析发现,超过60%的代表菌编码至少1个次级代谢产物基因簇,并从8个未可培养菌中发现了8个潜在的新颖次级代谢产物基因簇。人体肠道中的次级代谢产物主要由梭菌纲（Clostridia）、芽孢杆菌纲（Bacilli）、γ-变形菌纲（Gammaproteobacteria）、拟杆菌纲（Bacteroidia）、放线菌纲（Actinobacteria）和厚壁菌纲（Negativicutes）6类细菌编码的非核糖体多肽合成酶（nonribosomal peptide synthetase,NRPS）、细菌素、芳基多烯类化合物、萜烯、β-丙内酯、NRPS-样蛋白组成。经PathoFact预测分析发现,抗生素耐药基因和毒力因子在代表性菌株中分布广泛,但潜在病原菌编码频率更高。潜在病原菌中编码外膜蛋白、PapC N-端结构域、PapC C-端结构域、肽酶M16失活结构域等分泌型毒素和硝基还原酶家族、AcrB/AcrD/AcrF家族、PLD-样结构域、Cupin结构域、假定溶血素、S24-样肽酶、磷酸转移酶家族、内切核酸酶/外切核酸酶/磷酸酶家族、乙二醛酶/博莱霉素抗性等非分泌型毒素的频率较高。该研究将为进一步从肠道微生物组中挖掘新的微生物天然产物、了解肠道微生物的定殖与感染机制,为肠道微生物相关疾病提供靶向防治策略等奠定基础。     

昆虫共生菌的次级代谢产物研究进展

微生物与昆虫的共生是一种普遍现象,昆虫种类繁多,与昆虫共生的微生物也多种多样。昆虫共生菌是活性次生代谢产物的重要来源。本文对自2008年以来已报道的177个昆虫共生菌的次级代谢产物进行了统计和分析,结果表明:61.6%的化合物为新天然产物(生物碱类新化合物最多),其中,约75%的新化合物来源于昆虫共生真菌,25%来源于细菌;醌酮类化合物是昆虫共生菌源天然产物的主要结构类型,占23.2%;47.5%的化合物具有显著的抗肿瘤、抗菌、除草和抗氧化等生物活性,且化合物中的主要活性类型是抗菌和抗肿瘤活性,活性范围覆盖面最广的结构类型是生物碱类。以上结果表明昆虫共生菌的次级代谢产物是先导性化合物的重要来源且具有丰富的生物活性类型。本文以天然产物的结构分类为切入点,结合其研究菌株来源、生物活性等进行综述,旨在为充分挖掘昆虫共生菌次级代谢产物提供重要参考。     

微生物肽类次级代谢产物研究进展

微生物肽类次级代谢产物是一类重要的天然产物,因含有稀有氨基酸而具有丰富的化学结构和生物活性。随着微生物天然产物分离纯化技术的发展,新型肽类产物层出不穷,在微生物次级代谢产物的研究领域扮演了重要的角色。本文综述近年来发现的来自细菌和真菌的微生物肽类代谢产物,以及采用基因挖掘等手段人工合成的新型肽类产物,并结合近年来本团队昆虫病原线虫共生菌肽类产物的研究积累,分析微生物肽类产物研究存在的问题及可能的解决方案,以期为微生物导向的新型活性肽类产物的深入发掘和应用研究提供参考。     

大豆异黄酮微生物转化研究进展

大豆异黄酮是大豆在其生长过程中形成的一类次生代谢产物,具有抗氧化、抗癌、减少骨质流失、降低心脑血管发病率等多种生理功能。目前已知,被摄人机体的大豆异黄酮将被肠道微生物菌群转化为具有更高、更广生物学活性的不同产物。因此,大豆异黄酮对人体的有益调节作用强弱并不简单取决于摄人机体的净含量的多少,更在于被摄人机体的大豆异黄酮将如何被肠道菌群转化。本文从大豆异黄酮的组成与功能、大豆异黄酮体内吸收、代谢及微生物转化、转化产物的活性以及高效合成等方面进行了系统综述,对大豆异黄酮微生物生物转化研究现状和存在问题进行分析总结,并对今后发展趋势进行展望,旨在推动高活性大豆异黄酮微生物转化产物的研究与开发。     

肠道微生物代谢苷类化合物的研究进展CSCD

肠道微生物对苷类化合物的体内代谢十分重要,可分泌代谢酶进行脱糖基、脱甲基、脱羟基、水解和氧化还原等反应将苷代谢生成次级苷、苷元或其他代谢产物,从而促进苷类药物的吸收并发挥药效。本文论述了肠道微生物及代谢酶对苷类化合物代谢的意义,总结了肠道微生物对不同结构类型的苷类化合物的代谢规律及代谢产物,为了解苷类药物的疗效基础、作用机理及利用微生物转化开发苷类药物提供参考。     

丁酸菌与老年肠道功能的相关性

丁酸菌是一种专性厌氧芽胞杆菌,是以丁酸为主要代谢产物的益生菌,可定植于人体肠道,在某种程度上与乳酸菌有协同作用,可抑制人肠道内有害菌的生长、促进营养物质的吸收、改善肠道功能等。本研究主要对丁酸菌在临床中的应用研究进展进行综述,尤其是对丁酸菌与老年人肠道功能的相关性进行阐述,并展望丁酸菌对老年慢性疾病如糖尿病、心血管疾病、老年痴呆、风湿性疾病及骨质疏松症防治的研究未来。     

肠道菌群多糖利用及代谢

宿主与肠道共生菌之间存在一种互利共生的关系。肠道共生菌可以代谢宿主自身不能消化的多糖。进入肠道内的多糖是影响肠道共生菌生理状态和组成的重要因素,这些多糖主要来自饮食和宿主的粘膜分泌物。人类饮食中含有几十种不同的膳食多糖,其中大多数不能被人类基因组中编码的酶降解,并进入大肠,供肠道共生菌利用。肠道共生菌将这些不易消化的多糖转化为短链脂肪酸,作为大肠细胞和其他肠道上皮细胞的营养物质。除此之外,短链脂肪酸对人体健康有着重要的影响。不同的肠道共生菌对进入肠道内的多糖具有不同的偏好性,表明摄入膳食多糖是一种可以直接影响肠道内共生菌物种平衡的策略。因此,研究肠道菌群的多糖代谢机制具有重要的意义。本文从肠道共生菌的组成、利用进入肠道内多糖的机制,以及产生的代谢产物可能对人体健康存在的潜在影响等方面进行了综述,并介绍了代表性的肠道共生菌如拟杆菌和双歧杆菌利用多糖的途径及特征。     

基于UPLC法测定离体大鼠及人源肠道菌对三七中人参皂苷代谢的差异

为探究人与大鼠肠道菌群对三七水煎液中三醇型人参皂苷Rg1、Re及二醇型人参皂苷Rb1、Rd体外代谢的差异性及发现其代谢产物原人参二醇PPD与原人参三醇PPT,实验利用UPLC方法测定三七水煎液分别与人、大鼠肠道菌群在厌氧条件下共培养24h后的孵育液中4种皂苷的含量及代谢产物PPD与PPT的含量。结果表明三七中含有三醇型人参皂苷Rg19.4500mg/g、Re1.8872mg/g,二醇型人参皂苷Rb18.5816mg/g、Rd1.9456mg/g。与人源肠道菌共培养后,三七中含有的二醇型、三醇型人参皂苷含量显著降低,重要的是,在培养液中检测到代谢产物PPD和PPT的存在,含量分别为0.2136mg/g及0.0344mg/g,与大鼠肠道菌共培养后,三七中含有的二醇型皂苷含量有轻微降低,而三醇型皂苷含量未见明显变化,但有少量PPT(0.0184mg/g)的生成。由此可见:在体外条件下,三七水煎液中人参皂苷会被人肠道菌群降解生成代谢产物PPD和PPT,而大鼠肠道菌群的降解产物却仅有PPT生成,二者存在种属差异。     

Metabolite profiling of natural substances in human: in vitro study from fecal bacteria to colon carcinoma cells (Caco-2)

Flavonoids, including anthocyanins, are polyphenolic compounds present in fruits, vegetables and dietary supplements. They can be absorbed from the intestine to the bloodstream or pass into the large intestine. Various bacterial species and enzymes are present along the entire intestine. The aim of the present work was to investigate the intestinal metabolism of selected dietary polyphenol and polyphenol glycosides (quercetin, cyanidin-3-O-glucoside, cyanidin-3-O-galactoside, and delphinidin-3-O-galactoside) by human fecal bacteria. Moreover, the metabolism of metabolites formed from these compounds in human colon carcinoma cells (Caco-2) was also point of the interest. Test compounds were added to fresh human stool in broth or to Caco-2 cells in medium and then incubated for 6 or 20 h at 37°C. After incubation, samples were prepared for LC/MS determination. Main metabolic pathways were deglycosylation, hydrogenation, methylation, hydroxylation, and decomposition. 2,4,5-trihydroxybenzaldehyde, as a metabolite of cyanidin glycosides, was detected after incubation for the first time. Metabolites formed by fecal bacteria were further glucuronidated or methylated by intestinal enzymes. This metabolite profiling of natural compounds has helped to better understand the complex metabolism in the human intestine and this work also has shown the connection of metabolism of natural substances by intestinal bacteria followed by metabolism in intestinal cells.     

罗汉果皂苷V在人工胃液中的稳定性和体外代谢研究

为了研究罗汉果皂苷V在胃肠道中的稳定性及体外代谢特征,该研究首先考察罗汉果皂苷V在人工胃液中的稳定性,然后在体外模拟人肠内环境,研究人肠内细菌对该成分的代谢作用,并采用LCMS/IT-TOF液质联用仪分析了培养液中的化学成分,考察了罗汉果皂苷V在人工胃液和人肠道菌群培养液中的变化。结果表明:罗汉果皂苷V在人工胃液条件下,迅速发生酸水解反应,分别脱去3个糖苷、4个糖苷、5个糖苷及2个氢转化为二糖苷、一糖苷与脱氢苷元,其脱糖反应随着时间的延长而反应越完全,反应4 h后就只剩下苷元; 该化合物在人的肠道菌群作用下经过脱糖反应转化为四糖苷、三糖苷、二糖苷、一糖苷,经过糖苷化反应转化成六糖苷。通过体外实验,初步了解罗汉果皂苷V在胃液和肠道环境中的降解规律,该研究结果为今后探讨罗汉果皂苷在人体内的代谢与生物转化规律提供了物质和技术基础。     

降胆固醇乳酸菌的应用及其机理研究进展

乳酸菌除了能够改善肠道微生态环境促进人体健康外,有些乳酸菌还具有能降低人体血清胆固醇的特性。近年来许多研究都已证明某些乳杆菌、双歧杆菌及肠球菌等具有调节血脂代谢、降低人体血清胆固醇的能力。本文综述了降胆固醇乳酸菌的体外筛选模型及其降胆固醇的作用机理,以期为进一步开发相关产品提供技术依据。     

Nectar xylose metabolism in a rodent pollinator (Aethomys namaquensis): defining the role of gastrointestinal microflora using 14C-labeled xylose

The Namaqua rock mouse Aethomys namaquensis, a rodent pollinator of certain geoflorous Protea species, consumes nectar containing xylose. Xylose is not known to be efficiently utilized by mammals. However, it is fermented by certain bacteria, yeasts, and fungi, particularly gastrointestinal bacteria. The end products of microbial fermentation are utilized by the host in oxidative metabolism. Here we investigate the degree to which intestinal bacteria of A. namaquensis contribute to xylose metabolism. Mice were caught during Protea humiflora flowering and nonflowering seasons and given an oral dose of 14C-labeled xylose. Exhaled CO2 and excreted urine and feces were continuously collected for 30 h thereafter, and label recovery was determined. Each mouse was then treated with antibiotics to reduce gut microflora, and the experiment was repeated. With their natural gut flora population intact, mice caught during the flowering season exhaled significantly more 14CO2 than did mice caught during the nonflowering season. Also, during both seasons, mice exhaled significantly more 14CO2 before antibiotic treatment than after. Antibiotic treatment caused a significant increase in the proportion of 14C-labeled xylose that was excreted in the urine. The mouse diet likely influences the composition of the gastrointestinal community. Aethomys namaquensis relies on its gut microflora to ferment xylose, thereby converting it into end products that are used by the mice for metabolism.     

吲哚——种间及跨界信号分子新成员

吲哚作为一种典型的氮杂环芳烃化合物,在自然界中广泛存在。近年来,越来越多的研究表明吲哚具有一定的生物活性,是一种新型种间及跨界的信号分子。研究发现,吲哚不仅可以调节微生物的毒性、耐药性、生物膜形成以及群感效应等生理生化行为,调控植物生长发育和防御系统的形成过程,还能够影响动物的肠道炎症、细胞氧化压力及荷尔蒙分泌等生理健康。因此吲哚在微生物代谢、动物健康和植物生长等多个方面扮演了重要角色,具有重要的生物学及生态学双重意义。文中综述了吲哚从生物代谢到信号传递的研究历史,及其在微生物种内或种间以及微生物-动植物之间跨界的信号传导与调控作用的研究进展,旨在为揭示复杂环境中吲哚生物代谢及信号调控的生物学意义与生态学机制提供重要的理论指导。     

Ex-germfree mice harboring intestinal microbiota derived from other animal species as an experimental model for ecology and metabolism of intestinal bacteria.

Ex-germfree (GF) animals harboring intestinal microbiota derived from other animal species, e.g. human-flora-associated (HFA) and pig-flora-associated (PFA) mice, have been considered as a tool for studying the ecology and metabolism of intestinal bacteria of man and animals. Human fecal microbiota was transferred into the intestines of the mice with minor modification by inoculating GF mice with human fecal suspensions. Interestingly, bifidobacteria were eliminated from some of the HFA mouse groups, whereas other dominant bacterial groups remained constant. Elimination of bifidobacteria appeared to be dependent on the composition of microbiota in the inoculated sample. Human fecal microbiota established in the intestines of the HFA mice reproduced in the intestine of offspring of these HFA mice and of cage-mated ex-GF mice without any remarkable change in composition. Although the HFA mice could be used for studying the effects of diet on human intestinal microbiota, the metabolism of microbiota of HFA mice reflected that of human feces with respect to some metabolic activities but not others. PFA mice were also a good model for studying the ecosystem of pig fecal microbiota and the control of short chain fatty acids in pig intestines, but not for studying putrefactive products generated in pig intestines. In conclusion, HFA and PFA mice provide a stable and valuable tool for studying the ecosystem and metabolism of the human and animal intestinal microbiota, but they have some limitations as a model.     

氢气与肠道菌群的关系研究进展

目前,氢气已被证实在多种疾病中具有显著的医学效应,然而其发挥效应的分子机制并不清楚。肠道菌群被人们看作人体的一个重要“器官”,与人类健康的关系密不可分。研究表明,人类肠道菌群中存在着大量能够进行氢气代谢的菌群,这些菌群的变化可能与多种疾病的发生发展密切相关。此外,研究还发现外源氢气干预可能通过重塑肠道菌群改善炎症性肠病、脂肪性肝病等。综述了肠道菌群的氢气代谢及其与疾病发生发展的关系以及外源氢气干预通过调节肠道菌群影响疾病进展的相关研究,希望能为致力于从肠道菌群角度研究氢气医学效应的科研工作者提供帮助。     

The antimicrobial effects of glucosinolates and their respective enzymatic hydrolysis products on bacteria isolated from the human intestinal tract

Aims:  The aim of the study was to evaluate the in vitro antibacterial activity of glucosinolates and their enzymatic hydrolysis product against bacteria isolated from the human intestinal tract.
Methods and results:  Using a disc diffusion bioassay, different doses of intact glucosinolates and their corresponding hydrolysis products were tested. There were clear structure–activity and concentration differences with respect to the in vitro growth inhibition effects as well as differences in the sensitivities of the individual bacteria. The most effective glucosinolate hydrolysis products were the isothiocyanates; sulforaphane and benzyl isothiocyanate were the best inhibitors of growth. Indole-3-carbinol had some inhibitory effects against the Gram-positive bacteria but had no effect, even at the highest dose, against the Gram-negative bacteria. Indole-3-acetonitrile had some inhibitory activity against the Gram-negative bacteria. Glucosinolates, nitriles and amines were ineffective at all the doses used.
Conclusions:  Glucosinolate hydrolysis products and specifically the isothiocyanates SFN and BITC have significant antimicrobial activity against Gram-positive and Gram-negative bacteria, and might be useful in controlling human pathogens through the diet.
Significance and Impact of the Study:  This the first major in vitro study demonstrating the potential of these natural dietary chemicals as an alternative to, or in combination with, current antibiotic-based therapies for treating infectious diseases.     

Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health

The indigenous intestinal microflora are involved in a variety of processes within the human body, and are important for maintaining host health. As such, interindividual differences in the ability to harbor certain intestinal bacteria might be associated with interindividual differences in health and/or disease susceptibility. In the last decade there has been considerable interest in phytoestrogen intakes in relation to human health. Daidzein, an isoflavone phytoestrogen found in soy, is metabolized to equol and O-desmethylangolensin (O-DMA) by intestinal bacteria. The specific bacterium/bacteria responsible for equol and O-DMA production in humans have yet to be identified definitively, but in vitro and animal studies have suggested that equol and O-DMA are more biologically active than their precursor daidzein. Interestingly, substantial interindividual differences in daidzein metabolism exist; following soy or daidzein consumption, approximately 30%-50% of the human population produce equol, and approximately 80%-90% produce O-DMA. Observational and intervention studies in humans have suggested that the ability to produce equol and O-DMA may be associated with reduced risk of certain diseases including breast and prostate cancers. However, relatively few studies have been conducted to date. In this review, we discuss the available evidence for a relationship between daidzeinmetabolizing phenotypes and human health, and suggest potential mechanisms for some of the reported relationships.