肠道菌群与人体代谢

人体代谢是人为了适应环境变化通过自身与微生物基因组共调节产生的所有复杂化学反应的总称。无论疾病与否,规模宏大而复杂的细菌库——肠道菌群都直接参与人体多种代谢过程。肠道菌群在人体内形成了错综复杂的微生态系统,与人类共同变化应对外界因素,人体代谢平衡状况与肠道菌群的结构组成变化密不可分。研究肠道菌群与人体代谢的相关性,对于人类健康有重要意义。     

肠道菌群与中草药有效成分代谢

近年来,肠道菌群与中药有效成分代谢已成为众多学者研究的热点,本研究综述了肠道菌群对中药有效成分代谢转化、吸收利用的研究概括,以及中草药对肠道菌群的调理作用。     

基于肠道微生物组学和粪便代谢组学分析槲皮素对ApoE−/−动脉粥样硬化小鼠的影响

观察槲皮素对ApoE^−/−动脉粥样硬化（AS）小鼠肠道微生物及其代谢产物的影响。

选用14只8周龄雄性ApoE^−/−小鼠经12周高脂高胆固醇饲料喂养建立AS小鼠模型,采用随机数字表法将其随机分为模型组（M组）和槲皮素组（Q组）,每组7只,选用同龄雄性C57BL/6J小鼠8只作为对照组（C组）。Q组小鼠每天每只灌胃20 mg/kg槲皮素,C组和M组给予生理盐水,共8周。使用HE染色和Masson染色进行血管形态学观察。采用应激法无菌取小鼠粪便样本,通过16S rRNA测序检测粪便菌群,使用非靶向气相色谱−质谱法检测粪便样本代谢物。差异菌群和差异代谢产物的相关性采用Pearson相关性分析。

M组血管内有脂质沉积,胸主动脉纤维化显著,槲皮素干预后AS小鼠血管脂质沉积显著减少。M组与Q组ACE指数和Observed species指数差异具有统计学意义（P＜0.05）,β−多样性提示组间菌群组成存在差异。在属水平上,M组优势菌属有Ileibacterium、粪杆菌属、双歧杆菌属、Coriobacteriaceae UCG-002、罗姆布茨菌属、苏黎世杆菌属、Hydtogenibacillus和Haliangium;Q组优势菌属有另枝菌属、Lachnospiraceae NK4A136 group、Rikenellaceae RC9 gut group、理研菌属、埃希菌−志贺菌属、阿克曼菌属和Ruminiclostridium 9。共检测到2 570种代谢物,其中差异代谢物372种（P＜0.05,VIP＞1）。Q组阿克曼菌属与差异代谢产物D−葡萄糖胺酸（r=0.815,P＜0.001）、L−组氨醇（r=0.795,P＜0.001）呈正相关,与代谢物4−亚硝基二苯胺（r= −0.815,P＜0.001）呈负相关。

槲皮素可改变AS小鼠肠道菌群结构,改善动脉粥样硬化,调节脂质代谢和抗氧化应激。

     

微塑料暴露对小鼠肠道菌群分布及代谢途径的影响

研究微塑料对小鼠肠道菌群分布及代谢途径的影响,为进一步揭示微塑料对人类健康的影响奠定基础。

建立食用聚苯乙烯（polystyrene,PS）微塑料的小鼠模型,检测微塑料喂饲前后小鼠血糖血脂的变化;利用宏基因组测序技术检测正常饮食小鼠和PS微塑料喂饲小鼠肠道菌群的种类和差异,分析微塑料对小鼠肠道菌群代谢的影响。

与对照组相比,PS微塑料喂饲组小鼠血糖血脂水平无显著变化;在门水平上,子囊菌门相对丰度显著增加（t=−3.883,P=0.028）;在属水平上,鞘氨醇单胞菌属相对丰度显著增加（t=−5.917,P=0.003）,魏斯菌属相对丰度显著降低（t=−2.677,P=0.007）;在种水平上,解甘露醇罗尔斯顿菌相对丰度显著增加（t=−2.611,P=0.009）,约氏乳杆菌相对丰度显著降低（t=−1.984,P=0.047）。在属水平上,差异菌Massilistercora与LDL水平呈正相关（P＜0.001）,Ruthenibacterium、Phocaeicola等与TC水平呈负相关（均P＜0.010）;微塑料使正常小鼠多条代谢通路的相对丰度发生改变,可能会影响到正常代谢功能。

微塑料在一定范围内能改变正常小鼠肠道菌群结构组成,同时可以改变小鼠代谢通路变化,具体机制有待深入研究。

     

从肺肠关系探讨肠道菌群与儿童哮喘的关系

儿童哮喘是一种肺部疾病,肠道菌群在其免疫和代谢等诸多方面扮演着重要角色,肺肠之间微妙的关系可能是影响疾病发生、发展及预后的潜在机制。通过分析肺与肠的结构和功能,发现从中医学和现代医学角度均可证实肺肠具有表里同源关系。津液/黏液是肺肠之间的重要物质,影响哮喘儿童痰的生成及变化。肺肠之间的微生物可随津液/黏液定植,且菌群结构的变化又与儿童哮喘密切相关。基于肺肠结构关系及二者间物质的沟通作用,发现哮喘患儿不仅存在肠道菌群失衡,且肠道菌群与免疫应答和肠道代谢之间的关系,可能是防治儿童哮喘的新途径,值得进一步探索。

     

Role of metabolism by the human intestinal microflora in arbutin-induced cytotoxicity in HepG2 cell cultures

A possible role for metabolism by the human intestinal microflora in arbutin-induced cytotoxicity was investigated using human hepatoma HepG2 cells. When the cytotoxic effects of arbutin and hydroquinone (HQ), a deglycosylated metabolite of arbutin, were compared, HQ was more toxic than arbutin. Incubation of arbutin with a human fecal preparation could produce HQ. Following incubation of arbutin with a human fecal preparation for metabolic activation, the reaction mixture was filter-sterilized to test its toxic effects on HepG2 cells. The mixture induced cytotoxicity in HepG2 cells in a concentration-dependent manner. In addition, the mixture considerably inhibited expression of Bcl-2 together with an increase in Bax expression. Likewise, activation stimulated cleavage of caspase-3 and production of reactive oxygen species in HepG2 cell cultures. Furthermore, induction of apoptosis by the intestinal microflora reaction mixture was confirmed by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling assay. Taken together, these findings suggest that the human intestinal microflora is capable of metabolizing arbutin to HQ, which can induce apoptosis in mammalian cells.     

肠道菌群昼夜节律与宿主生物节律相互作用的研究进展

为了适应地球昼夜更替对机体的影响,哺乳动物进化出了一套内在的适应性计时机制,由此形成了生物钟系统（circadian clock）。昼夜节律作为该系统中的重要部分可与机体的代谢过程同步变化[1]。肠道菌群作为与机体共生的生物群落,在肠道功能方面发挥着重要作用。对肠道菌群的昼夜节律性波动以及与宿主生物节律之间的相互作用进行研究有重要意义。本文将着重阐述肠道菌群昼夜节律与宿主生物节律的相互作用,以及这种相互作用对宿主代谢的影响。     

肠道菌群在中药代谢中的作用

近年来,中药在疾病防治方面所发挥的巨大作用受到了广泛认可。科学合理地解释中药的作用机制将有助于提高其利用价值。越来越多的证据表明肠道菌群在中药治疗中起着至关重要的作用,是打开我国中医药宝库的一把钥匙。肠道菌群在中药成分代谢过程中发挥着复杂的作用：一方面,人类肠道菌群通过编码多种活性酶,促进了中药组分中的非碳水化合物小分子与碳水化合物在肠道中的代谢过程;另一方面,经肠道菌群代谢转化后产生的中药产物具有多种药理作用。因此,在未来中药研究中应更多地考虑肠道微生态因素,这有助于为中药的药理作用机制研究奠定新的科学基础。     

Planthopper "adaptation" to resistant rice varieties: changes in amino acid composition over time

The brown planthopper, Nilaparvata lugens, shows considerable geographic and temporal variability in its response to varieties of cultivated rice. N. lugens has repeatedly “adapted” to resistant rice varieties; however, the physiological changes underlying planthopper adaptation are poorly understood. Endosymbionts within planthoppers, such as yeast-like endosymbionts (YLS) could play a role as they produce essential amino acids for planthoppers. We used a full factorial study to determine how natal rice variety, exposed rice variety, YLS presence, and the number of reared generations affected nymphal development, planthopper total nitrogen content, and planthopper hydrolyzed amino acid profiles. Nymphal development was strongly influenced by a four-way interaction between the exposed rice variety, natal rice variety, number of reared generations, and YLS presence. While symbiosis improved nymphal performance in the 8th generation, it appeared to be a drain on nymphs in the 11th generation, when the aposymbiotic nymphs actually showed higher performance than the symbiotic nymphs. This suggests that the symbiotic relationship may be acting beneficially in one generation while acting as a drain during another generation. Aposymbiotic planthoppers reared for 11 generations had a higher proportional concentration of rare amino acids than those reared for 8 generations, indicating that the planthopper itself appears to improve its ability to acquire rare amino acids. Therefore, the change in amino acid composition of planthoppers suggests an underlying change in protein expression or amino acid metabolism over time.     

肠道微生态与子宫内膜癌发生发展相关性的研究进展

子宫内膜癌是女性常见的恶性肿瘤之一,发病率呈逐年上升趋势,其发生的危险因素多与脂质、激素等代谢紊乱和免疫失衡有关。肠道微生态作为存在着庞大微生物种群的内生态环境,参与多种代谢途径和免疫调节。近年来肠道微生态的研究已成为临床防治的前沿科学,肠道微生物组成改变和肠道内环境失衡在多种恶性肿瘤发生发展中的作用为探索子宫内膜癌与肠道微生态的相关性研究提供了良好的基础。本文就肠道微生态紊乱对子宫内膜癌发生发展机制的影响作一综述。

     

Transformation of Trichothecenes in Ileal Digesta and Faeces from Pigs

The capacity of pig gastrointestinal microflora to metabolise the trichothecenes 3-acetyl-deoxynivalenol (3-acDON) and nivalenol (NIV) was investigated. 3-acDON was deacetylated to DON in anaerobic incubations with pig faeces collected at different pig farms. Furthermore, both 3-acDON and NIV were metabolised to the corresponding de-epoxy metabolite in these incubates. Five pigs, in which the gastrointestinal microflora lacked the ability to transform 3-acDON and NIV to their corresponding de-epoxidated metabolites, were given low levels of DON in the feed for seven weeks. The gastrointestinal micro-organisms did not acquire the de-epoxidation ability during the seven week long exposure period. At the end of the exposure period, faeces from pigs with a known de-epoxidation ability was spread out in the pens and left for 24 hours. One week after the faeces had been spread out in the pens, the de-epoxidation ability was found in faecal incubations from four out of five experimental pigs. This change in metabolic ability of the intestinal de-epoxidation ability was not accompanied by any detectable changes in the DNA-profiles of the bacterial community composition. The results show that the intestinal de-epoxidation ability is common at pig farms in the Uppsala area, and that the ability may be transferred between pigs in a stock.     

运动与肠道菌群的相关性

肠道菌群与人体互相依存,与机体的感染、营养、免疫及代谢密不可分,在某些疾病的预防和治疗中有着非常重要的作用。肠道菌群具有易变性,它的种类和数量是由遗传和环境因素共同决定的,环境因素主要包括宿主健康状态和生活方式等。近来发现,生活方式与代谢性疾病的发生发展密切相关,而这些代谢性疾病的发生发展都与肠道菌群的改变有关。本研究就机体不同代谢状态下肠道菌群的变化以及运动这种生活方式直接对肠道菌群的影响进行综述。     

Purification, identification, and cloning of lysoplasmalogenase, the enzyme that catalyzes hydrolysis of the vinyl ether bond of lysoplasmalogen

Lysoplasmalogenase (EC 3.3.2.2 and EC 3.3.2.5) is an enzyme that catalyzes hydrolytic cleavage of the vinyl ether bond of lysoplasmalogen, forming fatty aldehyde and glycerophosphoethanolamine or glycerophosphocholine and is specific for the sn-2-deacylated form of plasmalogen. Here we report the purification, characterization, identification, and cloning of lysoplasmalogenase. Rat liver microsomal lysoplasmalogenase was solubilized with octyl glucoside and purified 500-fold to near homogeneity using four chromatography steps. The purified enzyme has apparent K(m) values of ～50 μm for both lysoplasmenylcholine and lysoplasmenylethanolamine and apparent V(m) values of 24.5 and 17.5 μmol/min/mg protein for the two substrates, respectively. The pH optimum was 7.0. Lysoplasmalogenase was competitively inhibited by lysophosphatidic acid (K(i) ～20 μm). The predominant band on a gel at ～19 kDa was subjected to trypsinolysis, and the peptides were identified by mass spectrometry as Tmem86b, a protein of unknown function. Transient transfection of human embryonic kidney (HEK) 293T cells showed that TMEM86b cDNA yielded lysoplasmalogenase activity, and Western blot analyses confirmed the synthesis of TMEM86b protein. The protein was localized in the membrane fractions. The TMEM86b gene was also transformed into Escherichia coli, and its expression was verified by Western blot and activity analyses. Tmem86b is a hydrophobic transmembrane protein of the YhhN family. Northern blot analyses demonstrated that liver expressed the highest level of Tmem86b, which agreed with tissue distribution of activity. Overexpression of TMEM86b in HEK 293T cells resulted in decreased levels of plasmalogens, suggesting that the enzyme may be important in regulating plasmalogen levels in animal cells.