平台化学品短链支链脂肪酸和短链支链醇的微生物代谢工程

短链支链脂肪酸和短链支链醇均为重要的平台化学品,是合成多种高附加值产品的前体物质,市场需求巨大。目前两者的生产主要是利用基于石化原料的化学合成法。化学合成法存在着严重依赖化石燃料、反应效率低以及极易造成环境污染等缺点。微生物代谢工程的快速发展为这些平台化学品的生产提供了一条极具潜力的生物合成路线。利用微生物代谢工程技术构建生产这些平台化学品的微生物细胞工厂具有绿色清洁、可持续发展和经济效益好等独特优势。本文系统综述了近年来微生物代谢工程技术在短链支链脂肪酸和短链支链醇合成方面的研究进展,包括所涉及的宿主菌株、关键酶、代谢途径及其改造等,并探讨了未来的发展前景。     

树舌发酵浸膏对肉鸡盲肠微生物菌群及SCFA的影响

为研究肉鸡日粮中添加树舌[Ganoderma applanatum(Pers.ex Gray.)Pat.]发酵浸膏对肉鸡盲肠道微生物菌群及短链脂肪酸的影响,选用1日龄AA肉鸡225只,随机分为5个处理组,即空白组(基础日粮)、抗生素组(基础日粮中添加5 mg/kg黄霉素)、3个剂量的GAC添加组(基础日粮中分别添加1.57,3.15,6.29 g/100 g的GAC),每个处理3组重复,每组重复15只。试验期42 d。结果表明:肉鸡21日龄时,各GAC添加组沙门氏菌显著低于空白组(P0.05);各GAC添加组乳酸杆菌显著高于空白组(P0.05);各GAC添加组盲肠乙酸、丙酸浓度显著高于空白组(P0.05);6.29%GAC添加组盲肠丁酸浓度显著高于空白组(P0.05)。肉鸡42日龄时,1.57%和6.29%GAC添加组沙门氏菌显著低于空白组(P0.05),6.29%GAC添加组效果较好;各GAC添加组乳酸杆菌显著高于空白组(P0.05)。1.57%与6.29%GAC添加组盲肠乙酸、丙酸浓度显著高于空白组(P0.05);各GAC添加组盲肠丁酸浓度显著高于空白组(P0.05)。以上结果提示,GAC在肉鸡生长过程中可以增加肠道短链脂肪酸浓度,促进肠道乳酸杆菌的增殖,抑制沙门氏菌的生长,具有改善肠道菌群的作用。     

博落回提取物替代抗生素对肉鸡生长性能、盲肠微生物及盲肠紧密连接的影响

【目的】本研究旨在探讨博落回提取物(Macleayacordataextract,MCE)替代促生长抗生素(Antibiotic growth promoters,AGPs)对黄羽肉鸡生长性能、盲肠微生物及紧密连接mRNA表达的影响。【方法】试验选取体重相近、体型均匀、健康状况良好的1日龄温氏新黄鸡二号公鸡300只,随机分为5组,每组6个重复,每个重复10羽。分别饲喂基础日粮(NC)、抗生素日粮(ANT,基础日粮添加50 mg/kg那西肽和50 mg/kg金霉素)和试验日粮(基础日粮中添加200、400、800 mg/kg MCE),试验期60 d。【结果】日粮添加400 mg/kg MCE替代AGPs显著降低了料肉比(P0.05),并显著增加了盲肠长度(P0.05)。日粮添加MCE显著提高了肉鸡盲肠食糜中Firmicutes细菌数量和ClostridiumclusterXIVa数量(P0.05);MCE替代AGPs显著降低了盲肠Escherichia coli数量(P0.05)。400 mg/kg和800 mg/kg MCE替代日粮中AGPs显著增加了肉鸡盲肠食糜中总短链脂肪酸、乙酸和丁酸含量(P0.05);400 mg/kg MCE替代AGPs显著提高了盲肠中支链脂肪酸异丁酸和异戊酸的浓度(P0.05)。日粮添加MCE显著上调了肉鸡盲肠Claudin-1、JAM2、ZO-1的mRNA表达量(P0.05),并降低了黏蛋白MUC2、MUC5ac和MUC13的表达量(P0.05)。【结论】MCE替代AGPs可通过提高盲肠有益菌数量和短链脂肪酸浓度,促进肠道发育,提升肠道屏障功能等途径,改善黄羽肉鸡生长性能,本研究中其最适添加量为400 mg/kg。     

老年小鼠肠道短链脂肪酸含量和菌群特征关联性探究

随着社会经济的发展,我国人口老龄化日益严重,衰老这个永恒的问题又一次引起人们的关注.肠道菌群失衡是衰老发生发展的关键因素,而短链脂肪酸(short chain fatty acids,SCFAs)是介导菌群影响机体的主要方式之一.研究衰老、肠道菌群及SCFAs三者之间的关系,能够为临床通过干预肠道菌群影响SCFAs含量...     

短链脂肪酸对肠黏膜屏障的影响

肠黏膜屏障具有将致病性抗原等肠内物质与内环境隔离的功能,以维持内环境的相对稳定和机体的正常生命活动。其功能的维持依赖于人肠黏膜上皮细胞、肠道内正常菌群、肠道内分泌物和肠相关免疫细胞之间的功能协调,而其功能的发挥又受体内许多信号分子的影响。短链脂肪酸（short-chain fatty acids,SCFAs）就是其中一种重要的信号分子。SCFAs是肠道菌群的主要代谢产物之一,是肠道菌群与宿主代谢相互作用的媒介。宿主体内的SCFAs主要来自肠道菌群对膳食纤维的酵解,越来越多的研究证实,SCFAs不仅可以被肠道菌群利用,还可调节肠黏膜屏障及多种组织器官的代谢。本文主要就SCFAs对肠黏膜屏障的影响进行综述。

     

黄芩提取物对人体肠道菌群及短链脂肪酸的影响

目的：通过人体肠道微生物生态模拟系统（SHIME）,探究黄芩提取物对人体肠道菌群中的厌氧菌菌群丰度和短链脂肪酸（SCFA）的影响。方法：采用体外模拟系统模拟人体肠道微生态。大肠模拟罐中接种人体粪便样本,待粪便中的微生物维持稳定后,添加黄芩提取物（3.2 g/d）连续干预7 d,使用平板计数法分析模拟系统中的总厌氧菌及乳酸菌的菌群丰度变化,分别使用脑心浸液培养基（BHI）、MRS培养基（MRS）接种菌液,并在厌氧箱中倒置培养48 h。使用气相色谱分析黄芩提取物干预前后的肠道菌群代谢产物SCFA（乙酸、丙酸、异丁酸、丁酸、异戊酸、戊酸、异己酸和己酸）的含量变化。结果：与第6天取样结果相比,第14天的取样结果黄芩提取物增加了乳酸菌在内的厌氧菌菌群丰度。SCFA中的丁酸含量显著上升（P＜0.01）,而异戊酸含量显著下降（P＜0.01）。乙酸没有显著差异。结论：黄芩提取物可能通过改善乳酸菌及总厌氧菌的菌群丰度,提高丁酸含量,达到治疗肠道疾病的功效,为中草药黄芩提取物的体内研究奠定基础。     

鸡肠道菌群和短链脂肪酸相互关系的研究进展

肠道是动物机体重要的消化和营养吸收器官。肠道菌群决定肠道健康,进而影响机体健康。近来关于肠道菌群的研究越来越多,且肠道菌群酵解底物产生的短链脂肪酸也备受人们关注。短链脂肪酸主要包括乙酸、丙酸、丁酸等及其盐类。在对肠道功效方面,短链脂肪酸发挥着重要作用,如氧化供能、维持水电解质平衡、调节免疫、抗病原微生物及抗炎、调节肠道菌群平衡、改善肠道功能等。因此,本文根据近年来国内外相关研究报道,综述了鸡肠道不同种类、含量的菌群对短链脂肪酸来源和吸收的影响;不同种类、含量和制剂形态的短链脂肪酸对肠道菌群影响的研究进展,为更好地了解鸡肠道菌群和短链脂肪酸的相互关系和提高禽类养殖水平提供理论指导。     

高脂饮食诱导肠道微生物代谢产物短链脂肪酸改变进而影响食物过敏的发生

通过回顾过敏性疾病以及高脂饮食、肥胖等的大量研究报告,探究高脂饮食以及高脂饮食带来的肥胖是否会对食物过敏的发生产生影响以及可能的机制。研究发现,高脂饮食可能会增加食物过敏发生率,降低食物过敏阈值,增加食物过敏的风险,并且高脂饮食对肠道微生物的影响是其中的一个原因。高脂饮食改变肠道微生物结构,导致短链脂肪酸产生差异,而短链脂肪酸通过G蛋白偶联受体、组蛋白乙酰化等途径引起Treg细胞分化、IgA产生以及致耐受性的DC细胞产生,影响肠道屏障的健康,因此,高脂饮食对肠道微生物结构的改变带来的短链脂肪酸的产生差异影响了肠道屏障的健康,进而导致食物过敏的阈值降低,易感性增加。     

短链脂肪酸受体GPR43的研究进展

短链脂肪酸受体(G protein-coupled receptor 43,GPR43)属于G蛋白偶联受体(G protein-coupled receptors,GPCR)家族,因其与脂肪和糖代谢相关,在过去的10年中其研究日益受到重视。研究表明,GPR43不仅可以通过参与调节食欲和胃肠肽的分泌来调节脂肪的分解与形成,最终与代谢性疾病如肥胖、2型糖尿病和心血管病的密切相关;而且GPR43还参与调节人身体血脂浓度和炎症发生过程,甚至还与细胞的癌变密切相关。GPR43作为糖代谢、脂肪代谢的重要调节受体,已经成为一个重要的药物筛选靶点。针对GPR43受体的研究现状进行了总结并对今后的应用研究进行了展望。     

短链脂肪酸对肠道动力影响的研究进展

人体的肠道不仅仅是消化吸收场所,也是大量微生物生存的家园.肠道作为人体最大的储菌库,其多种生理功能离不开复杂多变的肠道菌群和菌群代谢物(如短链脂肪酸等)的参与.短链脂肪酸是肠道菌群发酵膳食纤维产生的一类重要的信号分子,研究发现短链脂肪酸除参与维持人体肠道黏膜免疫屏障、调节体液及电解质平衡以及为肠上皮细胞提供能量外,...     

Analyses of short-chain fatty acids and exhaled breath volatiles in dietary intervention trials for metabolic diseases

As an alternative to pharmacological treatment to diseases, lifestyle interventions, such as dietary changes and physical activities, can help maintain healthy metabolic conditions. Recently, the emerging analyses of volatile organic compounds (VOCs) from breath and short-chain fatty acids (SCFAs) from plasma/feces have been considered as useful tools for the diagnosis and mechanistic understanding of metabolic diseases. Furthermore, diet-induced changes of SCFAs in individuals with diagnosed metabolic abnormalities have been correlated with the composition changes of the gut microbiome. More interestingly, the analysis of exhaled breath (breathomics) has gained attention as a useful technique to measure the human VOC profile altered as a result of dietary interventions. In this mini-review, we examined recent clinical trials that performed promising dietary interventions, SCFAs analysis in plasma/feces, and VOC profile analysis in exhaling breath to understand the relationship between dietary intervention and metabolic health.     

Simple inhibitors of histone deacetylase activity that combine features of short-chain fatty acid and hydroxamic acid inhibitors

Butyric acid and trichostatin A (TSA) are anti-cancer compounds that cause the upregulation of genes involved in differentiation and cell cycle regulation by inhibiting histone deacetylase (HDAC) activity. In this study we have synthesized and evaluated compounds that combine the bioavailability of short-chain fatty acids, like butyric acid, with the bidentate binding ability of TSA. A series of analogs were made to examine the effects of chain length, simple aromatic cap groups, and substituted hydroxamates on the compounds' ability to inhibit rat-liver HDAC using a fluorometric assay. In keeping with previous structure-activity relationships, the most effective inhibitors consisted of longer chains and hydroxamic acid groups. It was found that 5-phenylvaleric hydroxamic acid and 4-benzoylbutyric hydroxamic acid were the most potent inhibitors with IC₅₀'s of 5 μM and 133 μM respectively.     

The role of short-chain fatty acids in the interplay between diet,gut microbiota,and host energy metabolism

Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism.     

Effects of extrusion of corn on growth performance,nutrient digestibility and short-chain fatty acid profiles in the hindgut of weaned piglets

Abstract

The experiment was conducted to investigate the effects of different inclusion levels of extruded corn on growth performance, nutrient digestibility and short-chain fatty acids profiles in the hindgut of weaned piglets. Ninety weaning piglets (28 d of age; 8.21 ± 0.69 kg BW) were allotted to one of five dietary treatments only substituted for unprocessed corn at varying levels (0, 1/4, 2/4, 3/4, 4/4) with extruded corn in a 28-d experiment. On day 28, 30 piglets were killed to measure concentrations and molar ratios of short-chain fatty acids in the hindgut. From day 0 – 14, digestibility of DM, N and GE was increased linearly and diarrhea frequency was decreased due to the increasing inclusion levels of extruded corn. From day 14 – 28, digestibility of GE and N was enhanced linearly due to the increasing proportion of extruded corn. On day 28, as proportion of extruded corn increased, the level of butyrate in the caecum and colon was increased linearly and the relative proportion of propionate was reduced. Results indicated that increasing proportions of extruded corn had no effect on growth performance, but significantly improved digestibility of N and energy at day 10 of trial and may be advantageous to the intestinal health of piglets.     

短链脂肪酸调控骨代谢的作用及机制的研究进展

肠道菌群紊乱可导致宿主病理性骨质流失,其通过产生的代谢物从肠道扩散到体循环对骨代谢发挥重要的调控作用。短链脂肪酸（Short Chain Fatty Acids,SCFAs）是肠道细菌产生的代谢物家族中最受关注的代谢产物,近年来研究表明,SCFAs在骨代谢相关疾病的发生发展中具有重要调节作用。本文就其在骨骼系统中的作用、调节骨组织中细胞的机制及作为靶点防治骨代谢疾病骨质疏松的研究进行综述,并为此新兴且具有前景的研究领域在未来的基础研究和转化研究提供展望。     

Characterization of gut microbiota and short-chain fatty acid in breastfed infants with or without breast milk jaundice

This study aims to investigate the gut microbiota and metabolites in breastfed infants with breast milk jaundice (BMJ) using gut microbiome–metabolomics. Breastfed newborns diagnosed with BMJ and those without BMJ (control group) were enrolled. Faecal samples were collected from the participants and subjected to high-throughput sequencing of the 16s rDNA V3 and V4 regions of the gut flora and metabolomics of short-chain fatty acids (SCFAs). Proteobacteria, Fimicutes and Actinobacteria were the main bacteria at the phylum level. Eshcerichia-Shigella and Enterobacteriacea were the main bacteria at the genus level. The difference between the two groups was compared. Compared to the control group, the amount of Streptococcus was significantly increased while the amount of Enterococcus was significantly decreased in the faeces from infants with BMJ. Functional prediction analysis of 16S found that biosynthesis of penicillin and cephalosporin significantly increased in the BMJ group. Gas chromatography–mass spectrometry detection of SCFAs revealed that levels of acetic acid and propionic acid were significantly lower in the BMJ group than in the control group. The reduced levels of acetic acid and propionic acid may be related to the increase in Streptococcus and decrease in Enterococcus, both of which may contribute to BMJ.     

短链脂肪酸丁酸抑制动脉粥样硬化形成及其分子机制

本研究通过观察丁酸对动脉粥样硬化斑块形成以及肠道组织结构和功能的影响,探讨丁酸防治动脉粥样硬化的效应及可能机制.选取8周龄雄性载脂蛋白E基因敲除(apolipoprotein E-knockout,ApoE-/-)小鼠,随机分成对照组(高脂高胆固醇饲料+饮水中给予200 mmol/L氯化钠,n = 10)和丁酸组(高脂...     

Metabolic engineering of Escherichia coli for production of fatty acid short-chain esters through combination of the fatty acid and 2-keto acid pathways

Fatty acid short-chain esters (FASEs) are biodiesels that are renewable, nontoxic, and biodegradable biofuels. A novel approach for the biosynthesis of FASEs has been developed using metabolically-engineered E. coli through combination of the fatty acid and 2-keto acid pathways. Several genetic engineering strategies were also developed to increase fatty acyl-CoA availability to improve FASEs production. Fed-batch cultivation of the engineered E. coli resulted in a titer of 1008 mg/L FASEs. Since the fatty acid and 2-keto acid pathways are native microbial synthesis pathways, this strategy can be implemented in a variety of microorganisms to produce various FASEs from cheap and readily-available, renewable, raw materials such as sugars and cellulose in the future.     

In vitro gas production kinetics and short-chain fatty acid production from rumen incubation of diets supplemented with hop cones (Humulus lupulus L.)

The aim of this study was to assess the effects of hop cones (Humulus lupulus L.) from two varieties Aurora and Dana, differing in their α- and β-acid contents, on rumen microbial activity measured with in vitro gas production kinetics and short-chain fatty acids (SCFA) production. Hop cones were added to the total mixed dairy cow ration (CONT) in concentrations simulating a cow’s daily intake of 50, 100 and 200 g of hop cones – the concentrations of hop cones expressed on a substrate basis were 43, 82 and 153 mg/g of substrate. Substrates were anaerobically incubated in glass syringes, and gas production kinetic parameters were determined by fitting data with the Gompertz model. Gas produced after 24 h (Gas24), maximum fermentation rate (MFR) and time of maximum fermentation rate (TMFR) were calculated from the estimated gas production kinetic parameters. After 24 h of incubation, the fermentation liquids of each substrate were taken for the determination of SCFA. Increasing the hop cone concentration decreased the total potential gas production, Gas24, MFR and shortened TMFR. The highest hop cone concentration significantly decreased acetic and butyric acid productions and total SCFA production after 24 h of incubation, but not propionic acid production, resulting in a decreased ratio between acetic acid and propionic acid.