Intrinsic ageing of gut epithelial stem cells

The maintenance of integrity of gut epithelium is essential for the well being of the organism throughout life. Gut epithelium is maintained through a carefully controlled balance between cell loss and renewal, which is sustained by the proliferation of the epithelial stem cells. Although these stem cells show no intrinsic limit to their proliferative capacity, recent evidence indicates that they suffer important functional impairments during the course of ageing. This paper reviews what is currently known about intrinsic ageing of gut epithelial stem cells and its functional consequences.     

Ontogeny of the endocrine cells of the intestine and rectum of sea bass (Dicentrarchus labrax L.): an ultrastructural study

Several endocrine cell types were ultrastructurally characterized during the differentiation of the intestine and rectum of sea bass (Dicentrarchus labrax L.) larvae. Only one cell type (type I) was found in the posterior region of the undifferentiated gut of 5-day-old larvae (phase I). Types V and VI were found in both the intestine and rectum, types II, III and IV in the intestine, and types VII and VIII in the rectum of 9- and 12-day-old larvae (phase II), the rectum alone showing signs of functional differentiation. In phase III larvae, in which both the intestine and rectum were differentiated, types IX, X, XI, XII, XIII, XIV and XV were found in the intestine, only types X, XI and XII being seen in the rectum. Besides these, a new cell type, XVI, was observed in the intestine of 55- and 60-day-old larvae (phase IV), in which the digestive tract was completely differentiated. The endocrine cells appearing in phases I and II showed very scarce secretory granules and the ultrastructural features of undifferentiated cells. Some endocrine cell types in the earliest developmental stages were related to some of those found later. A maturational process of the endocrine cell types paralleled the differentiation of the intestine and rectum, with an apparent increase in the number of secretory granules accompanying organelle development.     

Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Progress, problems, and perspectives in diagnosis and treatment of Whipple's disease

Whipple's disease is a rare chronic infectious disorder first described in 1907 by G.H. Whipple. The disorder is caused by the newly identified bacterium Tropheryma whipplei and there is evidence that altered immune functions play a role in the manifestation of the disease. The organ systems mostly affected are the joints and the gut, and in the further course often also the heart, lung, brain, and eyes. The intestinal involvement occurs with abdominal pain and diarrhea, which leads to weight loss, malnutrition, and anemia. In some cases the infection spreads to the central nervous system, which may lead to loss of memory, confusion, or disturbances in gait. In the last few years, several steps towards an improved diagnosis of the disease and characterization of the causative bacterium have been made. While untreated disease may be lethal, treatment is often able to eradicate the organism. At present, therapy is based on observations in small patient groups and personal experience. There are different antibiotic therapy regimens often starting with intravenous application for 2 weeks followed by oral medication for 1 year. The first clinical therapy study is ongoing.     

毒死蜱对小鼠焦虑样行为以及肠道菌群的影响

目的 观察毒死蜱暴露致小鼠焦虑样行为及肠道菌群的影响,并探讨两者之间的关系。方法 30只8周龄雄性C57BL/6J小鼠,随机分为3组:对照组(CTL)、毒死蜱低剂量组(CPF2.5)和毒死蜱高剂量组(CPF5),分别灌胃植物油、毒死蜱2.5 mg/kg bw和毒死蜱5 mg/kg bw,1次/d,连续14 d。采用旷场实验(OFT)和高架十字迷宫实验(EPM)对小鼠焦虑样行为进行检测; 采用16S rDNA测序检测粪便肠道菌群变化; 用LEfSe筛选各组间差异菌群; 采用Spearman分析研究肠道差异菌和焦虑样行为指标之间的相关性。结果 与CTL相比,CPF2.5和CPF5小鼠进入旷场中心次数减少(F=6.404,P=0.042,P=0.002),在开臂的活动路程百分比、开臂停留时间百分比以及进入开臂次数百分比均降低(F=8.525,P=0.002,P=0.002; F=17.486,P<0.001, P<0.001; F=4.751,P=0.023,P=0.010),以上差异均有统计学意义。LEfSe 多级物种差异判别分析结果显示,Dubosiella、Muribaculum、Akkermansia等菌在对照组富集; Odoribacter、PrevotellaceaeUCG_001菌在CPF2.5组富集; Proteobacteria、Rhizobiaceae、Ochrobactrum、Rhizobiales菌在CPF5组富集。Spearman相关分析结果表明,Muribaculum与EPM开臂活动路程百分比和开臂停留时间百分比呈正相关(r=0.506, P=0.012; r=0.455, P=0.025),Odoribacter和EPM开臂停留时间百分比呈负相关(r=-0.486, P=0.016)。结论 毒死蜱暴露后引起的小鼠焦虑样行为改变可能与特定的肠道菌群丰度(Muribaculum和Odoribacter)改变相关。     

基于“人卧血归于肝”探讨睡眠障碍对代谢相关脂肪性肝病的影响

“人卧血归于肝”是睡眠与“肝”藏象功能的重要关联,也是肝主藏血、肝主疏泄的具体体现。现基于“人卧血归于肝” 梳理睡眠与“肝”藏象的必然联系,总结睡眠障碍对肝脏糖脂代谢紊乱的影响,指出睡眠障碍通过中枢调控系统引发进食异常从而增加肝脏代谢负担,并通过其诱发的免疫反应加重肝脏代谢紊乱和肝脏炎症,也可增加胰岛素抵抗引发糖脂代谢异常并增加肝脏脂肪堆积。除此以外,睡眠障碍还可通过影响肠道菌群的变化对脂肪的消化吸收促进肝脏脂肪变性。故以“人卧血归于肝”的理论引出睡眠对于肝脏疾病的重要作用,并以期为进一步探索中西医结合防治方案提供理论参考。     

学龄儿童肥胖与肠道菌群多样性及菌属丰度的关联研究

目的分析学龄肥胖儿童和正常体重儿童肠道菌群多样性差异, 识别肥胖儿童肠道特征菌属, 为后续相关机制研究和学龄儿童肥胖的防治提供依据。方法基于2016年在上海市嘉定区某小学建立的研究队列人群, 将2016-2018年3年均处肥胖状态的儿童共63名纳入肥胖组, 其中男生43名, 女生20名。在3年均为正常体重的儿童中, 根据年龄、性别和所在班级, 将其与肥胖组儿童进行1∶1匹配, 共选择63名纳入对照组。采用问卷收集儿童基本信息、饮食状况、母乳喂养等情况, 收集两组儿童的粪便样本并进行16S rDNA测序。对质量优化后的测序序列按照97%相似性进行可操作分类单元聚类及物种注释。分析肥胖组和对照组儿童肠道菌群多样性及菌属丰度差异。计算肠道菌群的Ace、Chao1、Shannon、Simpson 4种α多样性指数, 并利用主坐标分析, 在非加权Unifrac距离和加权Unifrac距离的基础上表示β多样性。使用相似性分析(ANOSIM)比较两组β多样性的差异。利用STAMP软件挑选出两组儿童共有菌属中的差异细菌, 并利用广义线性模型(GLM)分析肥胖与α多样性以及显著差异菌属的关联。结果肥胖组...     

Mechanisms linking gut microbial metabolites to insulin resistance

Insulin resistance is the rate-limiting step in the development of metabolic diseases, including type 2 diabetes. The gut microbiota has been implicated in host energy metabolism and metabolic diseases and is recognized as a quantitatively important organelle in host metabolism, as the human gut harbors 10 trillion bacterial cells. Gut microbiota break down various nutrients and produce metabolites that play fundamental roles in host metabolism and aid in the identification of possible therapeutic targets for metabolic diseases. Therefore, understanding the various effects of bacterial metabolites in the development of insulin resistance is critical. Here, we review the mechanisms linking gut microbial metabolites to insulin resistance in various insulin-responsive tissues.     

藏汉不同骨密度人群肠道菌群及粪便短链脂肪酸差异研究

目的 比对研究四川红原藏族与成都汉族不同骨密度人群肠道菌群及粪便短链脂肪酸差异,为通过调节肠道菌群预防不同人群骨质疏松积累资料。方法 选取红原藏族与成都汉族居民,测定其足跟骨骨密度,收集粪便与人口学信息,以藏族低骨密度个体为基础,依据年龄、性别、民族、是否服用抗生素四个维度进行倾向性评分获得研究人群,并按骨密度水平分组,测定粪便16S rRNA序列及短链脂肪酸的浓度与构成比,对比分析各组的差异。结果 红原藏族肠道菌群的物种丰度高于成都汉族。与汉族人群相比,藏族人群拟杆菌门相对丰度较高,变形菌门相对丰度较低（拟杆菌门:z = - 4.156,P＜0.001;z = - 3.226,P = 0.001;z = - 2.990,P = 0.002;变形菌门:z = - 4.409,P＜0.001;z = - 3.287,P = 0.001;z = - 2.392,P = 0.016）。柯林斯菌属是藏族中骨密度组优势菌属,瘤胃球菌属2和乳球菌属分别是汉族中、高骨密度组优势菌属。两组人群粪便短链脂肪酸比较,藏族三组骨密度人群乙酸、异戊酸浓度均低于汉族人群（乙酸:t = - 3.119,P = 0.003;t = - 3.056,P = 0.003;t = - 5.104,P＜0.001;异戊酸:z = - 3.822,P＜0.001;z = - 3.497,P＜0.001;z = - 2.158,P = 0.031）,但高、中骨密度组异丁酸、异戊酸、戊酸和己酸构成比高于汉族人群（异丁酸:z = - 3.693,P＜0.001;z = - 3.388,P = 0.001;异戊酸:z = - 3.748,P＜0.001;z = - 3.844,P＜0.001;戊酸:z = - 3.778,P＜0.001;z = - 3.966,P＜0.001;己酸:z = - 2.535,P = 0.011;z = - 3.570,P＜0.001） 结论 红原藏族和成都汉族不同骨密度组的肠道菌群及粪便短链脂肪酸含量和构成比不同,其与骨密度的关系值得进一步探讨。     

四种无胃真骨鱼肠道L细胞的免疫组织化学研究

应用免疫组织化学ＡＢＣ技术，用高血糖素抗血清对鲢，鳙，团头鲂，银鲫的肠道内分泌细胞进行了免疫组织化学研究。４种鱼肠道中均显示出Ｌ细胞，分布密度各不相同，鲢肠只发布最多，银鲫肠中最少，Ｌ细胞位于肠褶各部，染色深褐，细胞以两端皆具突起的梭形细胞为主，多位于肠上皮细胞之间并与之平行，亦有少数末见突起的椭圆形细胞，多分布于上皮基部近基膜处，部分Ｌ细胞横卧于上皮基部与基膜贴近，突起伸向相邻细胞。少数Ｌ细胞位