肠-肝轴与非酒精性脂肪性肝病

肠道菌群组成和数量的改变影响宿主的能量代谢、免疫应答和炎症反应状态。非酒精性脂肪性肝病患者常伴有小肠细菌过度生长或某些菌群种类和数量的改变,以及肠道黏膜通透性增加。肠道细菌通过增强肝脏脂肪合成、诱导机体胰岛素抵抗、激活天然免疫系统相关分子模式等机制,诱发肝脏炎症反应,启动纤维化进程,促进单纯性脂肪变向脂肪性肝炎发展。鉴定影响机体能量代谢和炎症反应的肠道菌群及其产物将为阐明肠-肝轴对肝脏炎症发生、发展所起的作用奠定基础,为揭示非酒精性脂肪性肝病发生、发展的机制开辟新思路,为该病的防治探索新策略。     

动物宿主-肠道微生物代谢轴研究进展

肠道中栖息着数量庞大且复杂多样的微生物菌群,在维持宿主肠道微环境稳态中发挥重要作用。微生物菌群可以利用宿主肠道的营养素,发酵产生代谢产物,与宿主机体形成宿主—微生物代谢轴(host-microbe metabolic axis)。该代谢轴既能影响营养素吸收和能量代谢,又可调控宿主各项生理过程。本文主要阐述宿主-肠道微生物代谢轴的概念、肠-肝轴、肠-脑轴、肠道微生物与宿主肠道代谢轴的互作以及对机体健康的影响。     

昆虫肠-脑轴的研究进展

肠-脑轴是大脑和肠道神经系统双向联系的通道,近年来关于肠道微生物与宿主的神经生理和行为之间关系的研究快速增长,成为学科领域研究热点和发展方向之一。肠-脑轴调控昆虫多种行为和生理功能,昆虫的生长发育、繁殖等都与肠道菌密不可分。本文综述了肠道微生物对昆虫觅食、运动、交配、攻击、学习和记忆行为以及社会性行为的影响,并且概述了以昆虫为模型,对肠-脑轴与人类神经性疾病相关性研究的进展。     

微生物-肠-脑轴的研究进展

肠道微生物群能够调节宿主肠道稳态,同时参与调节宿主神经系统功能和行为。肠道菌群失调可能导致宿主神经系统功能障碍,从而引发神经退行性疾病。因此,研究微生物在肠?脑轴中发挥的作用及其机制,靶向调控肠道微生物菌群结构和功能,将为神经系统疾病的诊断与治疗提供新的手段。近年来,有关肠道微生物与机体神经系统间的互作研究受到了广泛关注,然而其具体的调控机制还未明晰。因此,本文综述了肠道微生物对宿主神经健康的调节作用,以及肠道微生物与宿主间的互作在调节神经功能、行为的潜力等研究进展,为更好地了解肠道微生物在调控宿主神经系统功能和行为的作用机制提供参考。     

微生物-肠-脑轴与抑郁症中医药研究进展

肠道微生物-肠-脑轴因其在调节精神疾病中的可能生物学基础作用而受到越来越多的关注。肠道微生物与抑郁症等精神疾病密切相关,肠道微生物可通过与\"肠-脑轴\"交互作用影响抑郁症的发生和发展,然而,肠道微生物与抑郁症之间的具体相互作用及机制还未十分明晰。深入研究微生物-肠-脑轴和抑郁症之间的相互关系,有助于我们从另一个角度更为深刻地认识和阐明抑郁症这种精神疾病。调节肠道微生物组成来治疗、预防抑郁症等精神疾病是今后的研究方向之一,可为探索中医药治疗、预防抑郁症机理提供新的思路。     

微生物-肠-骨轴与骨质疏松疾病的研究进展

肠道微生物被称为人体的“第二基因库”,对骨质疏松症的治疗具有良好的辅助作用。其主要通过肠上皮屏障、免疫系统、内分泌系统及肠道菌群代谢产物等途径在肠-骨轴的作用下影响肠道与骨代谢之间的联系。新型的肠道微生物靶向疗法如益生菌、益生元和膳食补充剂已被证明可有效预防骨质流失,但其长期疗效及安全性仍需进一步加强。因此,本文结合国内外研究进展,就微生物-肠-骨轴在骨质疏松症中的主要作用进行探讨,为骨质疏松症的治疗提供新的思路。     

肠道菌群-肠-脑-肌轴信号交流的研究进展

肠道菌群及其代谢产物在老年神经退行性疾病、胃肠道疾病以及肌肉骨骼系统性疾病的发病与康复中的作用越来越受到关注。肠道菌群及其代谢产物可通过免疫、内分泌和神经系统等多种途径调节大脑神经或肌肉骨骼系统功能;反之,肠道、大脑或肌肉骨骼系统也可通过炎症、代谢或线粒体通路作用于肠道系统,调节肠道菌群微生态,形成肠道菌群与肠-脑、肠-肌、 肠-脑-肌之间的双向信号交流机制,从而影响机体健康。因此,本综述总结了肠道菌群如何通过代谢产物、肠道通透性和免疫-神经通路建立起肠-脑-肌之间的相互联系,为促进大脑神经的可塑性和改善肌肉健康提供新思路。     

基于脑-肠-微生物轴的肠易激综合征机制与治疗研究进展

肠易激综合征(irritablebowelsyndrome,IBS)是常见的功能性肠病之一,目前尚缺乏可用器质性疾病解释的临床特征,最新研究将其机制描述为脑-肠-微生物轴紊乱,强调了肠道微生物群在调节脑肠互动中的中介作用,而中医药对于脑肠稳态调节有着悠久广泛的治疗经验并取得了良好疗效,但两者关联性缺乏论述。因此,本文以脑肠轴为切入点,以肠道微生物作为介质,基于脑肠轴-中医药的良性互动,结合我们相关工作,综述了目前与脑-肠-微生物轴相关的IBS的中西医研究,为同行提供参考。     

粪菌移植通过微生物-肠-脑轴改善抑郁症的研究进展

人类粪菌移植(fecal microbiota transplantation,FMT)早在19世纪50年代的西方医学中便有临床应用.FMT已被证明可以很好地缓解艰难梭菌感染(Clostridium difficile infection,CDI)的胃肠道疾病,在调节微生物-肠-脑轴(microbiota-gut-br...     

根据“肠-肾轴”理论治疗慢性肾脏病的研究进展

有研究报道在慢性肾脏病的发生发展过程中可发现一系列肠道变化,并有学者用“肠-肾轴”理论阐述肾脏病中肠道的变化以及疾病过程中肾脏与肠道之间的联系,提示调节肠道菌群或可成为治疗慢性肾脏病的新方法.本文根据“肠-肾轴”理论,综述了在慢性肾脏病发展过程中肠道出现的变化,如肠内代谢物异常、肠道损伤以及肠道菌群失调等.以慢性肾脏病...     

A microbial metabolite remodels the gut-liver axis following bariatric surgery

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Evolution of substrate specificity for the bile salt transporter ASBT (SLC10A2)

The apical Na(+)-dependent bile salt transporter (ASBT/SLC10A2) is essential for maintaining the enterohepatic circulation of bile salts. It is not known when Slc10a2 evolved as a bile salt transporter or how it adapted to substantial changes in bile salt structure during evolution. We characterized ASBT orthologs from two primitive vertebrates, the lamprey that utilizes early 5α-bile alcohols and the skate that utilizes structurally different 5β-bile alcohols, and compared substrate specificity with ASBT from humans who utilize modern 5β-bile acids. Everted gut sacs of skate but not the more primitive lamprey transported (3)H-taurocholic acid (TCA), a modern 5β-bile acid. However, molecular cloning identified ASBT orthologs from both species. Cell-based assays using recombinant ASBT/Asbt's indicate that lamprey Asbt has high affinity for 5α-bile alcohols, low affinity for 5β-bile alcohols, and lacks affinity for TCA, whereas skate Asbt showed high affinity for 5α- and 5β-bile alcohols but low affinity for TCA. In contrast, human ASBT demonstrated high affinity for all three bile salt types. These findings suggest that ASBT evolved from the earliest vertebrates by gaining affinity for modern bile salts while retaining affinity for older bile salts. Also, our results indicate that the bile salt enterohepatic circulation is conserved throughout vertebrate evolution.     

Evidence for the Existence of a Soybean Resistant Protein That Captures Bile Acid and Stimulates Its Fecal Excretion

Feeding HMF, an insoluble “high-molecular-weight fraction” from an industrial enzymatic digest of a soy protein isolate, increased the fecal excretion of bile acid concomitant with increased fecal nitrogen. An amino acid analysis revealed that this increased fecal nitrogen could be explained by an increase in the insoluble protein fraction. This suggests the existence of an indigestable protein or peptide that can be called a “resistant protein” in the feces. The presumed resistant protein was rich in hydrophobic amino acids and bound bile acid by hydrophobic interaction. The residual fraction of HMF obtained after in vitro pepsin and pancreatin digestion, showed higher in vitro bile acid-binding capacity and excreted more bile acid in vivo than HMF. Its amino acid composition was similar to that of the feces of rat fed with HMF. These results suggest that the fecal resistant protein with bile acid-binding ability could be derived from the indigestable fraction of HMF.     

Purification and Some Properties of Dipeptidyl Carboxypeptidase from Bacillus pumilus

An intracellular protease from a bacterium, Bacillus pumilus HL721, was purified about 5000-fold by Chromatography with a Q-Sepharose Fast Flow column, TSK-gel HA-1000 glass column, and TSK-gel G3000SWXL column using Bz-Gly-Ala-Pro as a substrate. The enzyme was the most active at pH around 7.5 and stable from 4.5 and 8.0. The enzyme activity was inhibited by Cu²⁺, EDTA, N-ethylmaleimide, o-phenanthroline, and p-chloromercuribenzoic acid. The molecular weight of the enzyme was 155,000 by gel filtration. The enzyme removed dipeptide from the carboxyl end of some peptides used as substrates. From these results the enzyme seems to be a dipeptidyl carboxypeptidase.     

肠道菌群来源细胞外囊泡在肝脏疾病中的作用研究进展

细胞外囊泡(extracellular vesicles, EVs)是一类具有脂质双分子层的膜性囊泡,可以被各种类型细胞分泌,是生物体通信的重要介质,参与原核生物和真核生物细胞之间的信号传输。在肠道微生态中,微生物-宿主的双向通信通常不需要细胞直接接触,微生物群来源EVs是这种“跨界”对话的关键参与者。肠-肝轴是连接肠道微生物与肝脏的桥梁,参与包含酒精性脂肪性肝病在内的多种肝脏疾病的发生与发展,近年研究发现肠道菌群来源的EVs在肝脏疾病的进程中具有重要的调控作用。本文概述了肠道菌群来源EVs的研究进展,特别是EVs的产生机制、包裹的内容物、在细菌-宿主互作以及在肝脏疾病中的作用。