肠道菌群与肠黏膜免疫

肠道不仅是吸收、消化和营养物质交换的重要场所 ,也是人体最大的免疫器官。人的肠黏膜面积巨大 ,约 2倍于皮肤的表面 ,每时每刻黏膜都要接触大量抗原 ,担负着重要的免疫功能。越来越多的证据表明肠黏膜免疫功能与寄居在肠道中为数众多的肠道菌群 (intestinalflora)有密切关系。本文就该领域的研究作一综述。1　肠道菌群的变迁与肠黏膜屏障人出生时肠道是无菌的 ,肠道菌群定植开始于出生后。菌群的发展和肠黏膜屏障的建立是一个渐进而互动的过程。母亲的肠菌群是新生儿肠道定植细菌的重要来源。定植也取决于环境因素。最初 ,任何厌氧菌都可…     

肠道菌群与肠道黏膜免疫系统的相互作用机制

胃肠道微生物生态系统是人和动物体内最复杂和最大的微生态系统,据估计,成人肠道内含有超过500种细菌。新生儿出生时胃肠道是无菌的,免疫系统几乎没有发育,但很快有种类繁多的细菌定植。随着细菌的定植,肠道菌群的建立,刺激机体产生大量的淋巴细胞和淋巴组织,促进全身免疫系统和黏膜免疫系统的正常发育并逐步成熟,     

清胰汤加减对急性胰腺炎患者肠道菌群及肠黏膜功能的影响

探讨清胰汤加减对急性胰腺炎患者肠道菌群及肠黏膜功能的影响,为该类患者的治疗提供参考。

选取我院2020年1月至2022年6月收治的急性胰腺炎患者108例,随机分为联合组（54例）和常规组（54例）。常规组患者采用常规西药治疗,联合组患者给予清胰汤加减联合常规西药治疗。比较2组患者治疗前后的中医症状积分、肠道菌群数量、肠黏膜功能（D-乳酸、二胺氧化酶、内毒素、白介素-6）情况,比较2组患者临床疗效及不良反应。

治疗后,2组患者主症、次症积分均降低,且联合组低于常规组（均P＜0.05）。治疗后,2组患者肠道大肠埃希菌、葡萄球菌属数量均降低,且联合组上述菌群数量均低于常规组（均P＜0.05）。治疗后,2组患者肠道双歧杆菌属、乳杆菌属数量均升高,且联合组上述菌群数量均高于常规组（均P＜0.05）。治疗后,2组患者血清D-乳酸、二胺氧化酶、内毒素、白介素-6水平均降低,且联合组均低于常规组（均P＜0.05）。联合组患者临床有效率高于常规组（96.30% vs 83.33%,P＜0.05）,而2组患者不良反应发生率比较差异无统计学意义（P＞0.05）。

清胰汤加减对急性胰腺炎患者的治疗效果显著,能够显著改善患者肠黏膜功能,调节肠道菌群水平,安全性较高。

     

肠道菌群与肠黏膜免疫及相关肠道疾病的研究进展

肠道菌群与肠黏膜免疫之间存在密切的关系,二者相互促进、相互影响,共同维持肠道微生态的平衡,二者失衡可造成肠道器质性及功能性的病变。对肠道菌群、肠黏膜免疫及相关肠道疾病的研究进展作一综述。     

术前补充益生菌对肠道手术患者术后肠道菌群及肠黏膜屏障功能的影响

目的 探讨术前补充益生菌对肠道手术患者术后肠道菌群及肠黏膜屏障功能的影响。方法 选取肠道手术患者86例,随机分为观察组和对照组各43例。两组患者术前予以常规肠道准备,术后给予等营养支持及抗生素等治疗。观察组患者术前7 d开始加用双歧杆菌三联活菌胶囊温水口服,630 mg/次,2次/d。观察两组患者术后肠道功能恢复及感染并发症情况,并比较术前7 d及术后首次自然排便时两组患者肠道菌群数量及肠黏膜屏障指标变化。结果 观察组患者术后肠鸣音恢复时间、肛门排气时间、排便时间均短于对照组（均P0.05）。术后首次自然排便时两组患者血清D-乳酸和DAO水平高于术前7 d时（P<0.05）,且观察组患者术后D-乳酸和DAO水平低于对照组（P<0.05）。结论 肠道手术患者术前补充益生菌可调节肠道菌群,降低肠黏膜通透性,改善其肠道功能,减少术后感染并发症的发生率。     

山西省健康人群的肠道菌群组成特征

目的探索山西省健康人群的肠道菌群组成特征及性别和年龄对肠道菌群组成的影响。方法应用16S rRNA基因测序技术,对山西省99名健康个体的粪便细菌DNA进行测序分析。结果山西省健康人群的肠道菌群在属水平分为两个集群,相对丰度最高的分别是拟杆菌属和普氏菌属;在区分这两个集群中,拟杆菌属与普氏菌属的曲线下面积（AUC）分别是0.97、1.00。男性组与女性组的物种丰富度（richness）和多样性（diversity）差异都无统计学意义（均P>0.05）,基于Bray-Curtis距离的主坐标分析（PCoA）图显示两组人群的样本分布没有明显分离（相似性分析：r=-0.0296,P>0.05）,LEfSe分析显示与性别分组有关的细菌很少。30-39岁、40-49岁和50-59岁三组人群的物种丰富度和多样性差异都无统计学意义（均P>0.05）,基于Bray-Curtis距离的PCoA图显示三组人群的样本分布没有明显分离（相似性分析：r=0.0109,P>0.05）,LEfSe分析显示几乎没有与年龄分组有关的细菌。结论山西省健康人群的肠道菌群更倾向分为两种肠型（拟杆菌型和普氏菌型）。性别对肠道菌群组成可能没有显著影响,30-59岁人群的肠道菌群组成比较稳定     

壳寡糖对环江香猪生化参数及肠道菌群组成的影响

为了探讨壳寡糖(COS)用作环江香猪饲料添加剂的可行性,试验选用21日龄断奶的环江香猪12头,随机分为2组,每组6头,分别饲喂添加0.5%COS的基础日粮和添加抗生素的基础日粮,试验期为14 d。试验结束时采集仔猪血液,肝素抗凝,离心分离血浆,测定生化参数;处死后取回肠和盲肠内容物,用荧光定量PCR测定其中双歧杆菌、乳酸杆菌、链球菌、大肠杆菌和总细菌的数量。结果表明,与对照组相比,壳寡糖组仔猪碱性磷酸酶活性显著增加(P<0.05),血氨和尿素氮含量有降低趋势(P>0.05);壳寡糖组回肠乳酸杆菌数量显著增加、链球菌数量显著降低(P<0.05),盲肠双歧杆菌和乳酸杆菌数量显著增加、大肠杆菌和链球菌数量显著降低(P<0.05)。上述结果提示,壳寡糖可在一定程度上改善环江香猪蛋白质代谢和肠道菌群平衡,从而增强其肠道健康。     

肠道菌群影响黏膜屏障结构与功能的研究进展

肠道黏膜屏障具有防止致病性抗原侵入、维护肠道健康的功能。而肠道菌群是肠道黏膜屏障的重要构成部分,肠道菌群失调会导致肠道黏膜屏障的损伤,引起炎性肠病、肠易激综合征及肝、肾等多种疾病的发生发展。因此,本文从肠道黏膜的结构与功能及肠道菌群对其的影响等方面归纳总结肠道菌群对屏障系统的调控作用,从调节肠道微生态平衡、促进黏液分泌、影响紧密连接和肠道上皮通透性、激发肠黏膜免疫、调控肠上皮凋亡、影响肠上皮DNA稳定性及产生特殊代谢产物等方面阐述其作用机制,为临床胃肠道疾病及其并发症的治疗提供新的思路和方法。     

双歧三联活菌胶囊对结肠造口术后腹泻患者肠道菌群及肠黏膜屏障功能的影响

目的 探讨双歧三联活菌胶囊对结肠造口术后腹泻患者肠道菌群及肠黏膜屏障功能的影响。方法 选取外科门诊就诊结肠造口术后腹泻患者82例,随机分为观察组和对照组各41例。两组患者均予以口服补液盐、止泻药等常规治疗。观察组加用双歧三联活菌胶囊温水口服,630 mg/次,2次/d,连用4周。于治疗前后观察两组患者肠道菌群数量及肠黏膜屏障功能指标的变化,并比较其临床效果。结果 治疗4周后,两组患者双歧杆菌、乳杆菌数量及B/E比值上升,大肠埃希菌和肠球菌数量下降（P<0.05）,且观察组变化幅度更大;两组患者血清D-乳酸和二胺氧化酶（DAO）水平降低（P<0.05或P<0.01）,且观察组下降幅度更大（P<0.05）;在总有效率上观察组较对照组更佳（P<0.05）。结论 双歧三联活菌胶囊治疗结肠造口术后腹泻患者效果较佳,机制与其能调节肠道微生态平衡紊乱,重建肠道微生态平衡,并能保护与修复肠黏膜屏障,减少其通透性,改善肠道功能密切相关。     

肠道菌群和肠黏膜屏障在类风湿关节炎中的作用CSCD

类风湿关节炎（rheumatoid arthritis,RA）是一种自身免疫性疾病,致畸率与致残率较高,发病机制尚不清楚,目前尚未有特效药可完全治愈。近年来,国内外相关研究表明RA的发病机制与肠道菌群和肠黏膜屏障密切相关。积极调节肠道菌群和改善肠黏膜屏障可有效缓解RA的关节炎症状,这可能作为RA干预的新靶点。肠道菌群失调引起肠道微生态失衡,一系列有害物质侵入并诱发肠道炎症反应,导致肠道黏膜屏障功能障碍,可能参与RA的发病,但具体作用机制还需进一步明确。本文对肠道菌群和肠黏膜屏障在RA中的具体作用及影响进行总结归纳,以期为治疗RA提供新方向。     

常乐康对乙肝肝硬化患者肠道菌群和肠道黏膜屏障功能的影响

目的探讨常乐康对乙肝肝硬化患者肠道菌群及肠道黏膜屏障功能的影响。方法收集乙肝肝硬化代偿期患者87例,其中治疗组48例,对照组39例。所有患者给予相同的常规护肝对症治疗,其中治疗组加用常乐康治疗8周。治疗结束后观察患者肠道菌群、肠道黏膜屏障功能和系统性炎症反应的改善情况。结果常乐康治疗后,患者肠道菌群中梭菌属I簇和XI簇及双歧杆菌属细菌数量显著升高,而肠杆菌科细菌及肠球菌属细菌数量显著降低;患者血清D-乳酸,内毒素(LPS)和二胺氧化酶(DAO)的水平显著下降,血清中促炎因子TNF-α和IFN-γ水平显著下降,而抗炎因子IL-10水平显著上升。结论常乐康可显著改善乙肝肝硬化患者肠道菌群组成和肠道黏膜屏障功能,有效减轻系统性炎症反应,可作为阻止乙肝肝硬化病情进展的有效辅助治疗方法。     

Feeding Jerusalem artichoke reduced skatole level and changed intestinal microbiota in the gut of entire male pigs

Different levels of dried Jerusalem artichoke were fed to entire male pigs 1 week before slaughter. The objective was to investigate the effect on skatole level in the hindgut and in adipose tissue, as well as the effect on microflora and short-chain fatty acids (SCFA) in the hindgut. Five experimental groups (n = 11) were given different dietary treatments 7 days before slaughtering: negative control (basal diet), positive control (basal diet + 9% chicory-inulin), basal diet + 4.1% Jerusalem artichoke, basal diet + 8.1% Jerusalem artichoke and basal diet + 12.2% Jerusalem artichoke. Samples from colon, rectum, faeces and adipose tissue were collected. Effect of dietary treatment on skatole, indole and androstenone levels in adipose tissue and on skatole, indole, pH, dry matter (DM), microbiota and SCFA in the hindgut was evaluated. Feeding increasing levels of Jerusalem artichoke to entire male pigs reduced skatole in digesta from colon and in faeces (linear, P < 0.01). There was also a tendency towards a decreased level of skatole in adipose tissue (linear, P = 0.06). Feeding Jerusalem artichoke decreased DM content in colon and faeces and pH in colon (linear, P < 0.01). Increasing levels of Jerusalem artichoke resulted in a reduced level of Clostridium perfringens in both colon and rectum (linear, P < 0.05) and a tendency towards decreased levels of enterobacteria in colon (linear, P = 0.05). Further, there was an increase in total amount of SCFA (linear, P < 0.05), acetic acid (linear, P < 0.05) and valerianic acid (linear, P < 0.01) in faeces. In conclusion, adding dried Jerusalem artichoke to diets for entire male pigs 1 week before slaughter resulted in a dose-dependent decrease in skatole levels in the hindgut and adipose tissue. The reduced skatole levels might be related to the decrease in C. perfringens and the increase in SCFA with subsequent reduction in pH.     

Effects of sodium butyrate and salinomycin upon intestinal microbiota,mucosal morphology and performance of broiler chickens

The effect of dietary sodium butyrate (SB) or salinomycin (SAL) or both additives on performance, small intestinal morphology and microbial ecology of broiler chickens was studied. A growth trial was conducted with 96 Ross 308 female broilers from 1 to 30 days of age. Four treatment groups were fed with a non-supplemented control diet or three experimental diets supplemented with i) 300 mg SB (Adimix 30 coated) per kg, ii) 60 mg SAL (Sacox) per kg or iii) both additives in combination. Feed intake and body-weight gain decreased and gain-to-feed ratio increased due to SAL supplementation, while addition of SB did not affect performance in comparison with the control diet but positively affected feed intake and body-weight gain in comparison with birds fed the SAL-supplemented diet. Villus height in jejunum decreased, while crypt depth increased due to SAL supplementation. Addition of SB increased crypt depth in jejunum. No significant effect of either additive was observed in ileum morphology. Total short-chain organic acids concentration in ileal digesta decreased with SAL supplementation, mainly due to lower lactic acid concentration, but no effects were observed in the caeca. The SAL supplementation was accompanied by a pH increase in ileum and a pH decrease in caecum. No significant effect of SB addition was observed for these parameters. Total bacterial numbers and Lactobacillus [lactic acid bacteria (LAB)] counts in ileal and caecal contents were lower in birds fed with SAL-supplemented diet in comparison with birds fed with control or SB diet. DNA fingerprints revealed SAL supplementation to affect the microbial population by suppressing dominating LAB, potentially L. aviarius. The presented results show that dietary SAL, supplemented alone or in combination with SB, suppressed the microbial activity and altered the microbial community structure mainly in ileum. SAL alone negatively affected feed intake and body-weight gain; however, the effect was ameliorated by SB supplementation.     

消化道微生物区系与肥胖关系的研究进展

肥胖以及与肥胖相关的一些疾病威胁着发达国家和发展中国家,这些疾病包括Ⅱ型糖尿病、高血压、心血管疾病、非酒精型脂肪肝。最新研究表明消化道微生物区系(microbiota,指一个特定区域中所有活的微生物群落的统称。)可能与宿主肥胖相关。目前此类研究尚处于起步阶段,作者总结了以往研究结果,对消化道微生物区系的组成和作用、与宿主能量代谢相关的消化道微生物种类和作用、消化道微生物区系影响宿主能量储存的途径作了较为详细的介绍。并探讨了目前研究中存在的问题,总结了本实验室已有研究成果,以及今后可能的研究方向。     

体外法探究不同氨基酸形式酪蛋白水解物对猪小肠微生物的影响

【目的】通过体外法探究猪小肠不同肠段肠腔微生物和肠壁微生物对两种不同氨基酸形式的酪蛋白水解物的发酵特性。【方法】以生长猪的十二指肠、空肠、回肠肠腔食糜或者肠壁微生物为接种物,分别以酸水解酪蛋白(以游离氨基酸为主)和酶水解酪蛋白(以小肽为主)为底物,37°C厌氧培养发酵,于0、3、6、12 h采样,测定微生物蛋白(MCP)以及用real time-PCR进行菌群分析。【结果】(1)肠腔微生物发酵不同酪蛋白水解物:十二指肠和回肠酶水解酪蛋白组MCP的含量显著高于酸水解酪蛋白组(P0.05)。十二指肠酶水解酪蛋白组总菌、Firmicutes数量显著高于酸水解酪蛋白组(P0.05)。回肠发酵6 h后,酶水解酪蛋白组Escherichia coli和Firmicutes的数量显著高于酸水解酪蛋白组(P0.05);发酵12 h后,酶水解酪蛋白组总菌、Lactobacillus、E.coli的数量均显著高于酸水解酪蛋白组(P0.05)。(2)肠壁微生物发酵不同酪蛋白水解物:发酵12 h后,十二指肠和回肠酶水解酪蛋白组MCP含量显著高于酸水解酪蛋白组(P0.05)。十二指肠酶水解酪蛋白组Lactobacillus、Firmicutes数量分别极显著、显著高于酸水解酪蛋白组;回肠Firmicutes数量在酶水解酪蛋白组显著高于酸水解酪蛋白组(P0.05)。【结论】十二指肠和回肠的肠腔和肠壁微生物都能够利用小肽,且在一定程度上对小肽的利用更具优势。     

Early intervention with faecal microbiota transplantation: an effective means to improve growth performance and the intestinal development of suckling piglets

Recent studies indicate that early postnatal period is a critical window for gut microbiota manipulation to optimise the immunity and body growth. This study investigated the effects of maternal faecal microbiota orally administered to neonatal piglets after birth on growth performance, selected microbial populations, intestinal permeability and the development of intestinal mucosal immune system. In total, 12 litters of crossbred newborn piglets were selected in this study. Litter size was standardised to 10 piglets. On day 1, 10 piglets in each litter were randomly allotted to the faecal microbiota transplantation (FMT) and control groups. Piglets in the FMT group were orally administrated with 2ml faecal suspension of their nursing sow per day from the age of 1 to 3 days; piglets in the control group were treated with the same dose of a placebo (0.1M potassium phosphate buffer containing 10% glycerol (vol/vol)) inoculant. The experiment lasted 21 days. On days 7, 14 and 21, plasma and faecal samples were collected for the analysis of growth-related hormones and cytokines in plasma and lipocalin-2, secretory immunoglobulin A (sIgA), selected microbiota and short-chain fatty acids (SCFAs) in faeces. Faecal microbiota transplantation increased the average daily gain of piglets during week 3 and the whole experiment period. Compared with the control group, the FMT group had increased concentrations of plasma growth hormone and IGF-1 on days 14 and 21. Faecal microbiota transplantation also reduced the incidence of diarrhoea during weeks 1 and 3 and plasma concentrations of zonulin, endotoxin and diamine oxidase activities in piglets on days 7 and 14. The populations of Lactobacillus spp. and Faecalibacterium prausnitzii and the concentrations of faecal and plasma acetate, butyrate and total SCFAs in FMT group were higher than those in the control group on day 21. Moreover, the FMT piglets have higher concentrations of plasma transforming growth factor-β and immunoglobulin G, and faecal sIgA than the control piglets on day 21. These findings indicate that early intervention with maternal faecal microbiota improves growth performance, decreases intestinal permeability, stimulates sIgA secretion, and modulates gut microbiota composition and metabolism in suckling piglets.     

粪菌移植对非酒精性脂肪肝大鼠肠黏膜的保护作用

目的探讨粪菌移植(fecal microbiota transplantation,FMT)对非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)大鼠肠黏膜屏障的保护作用。方法健康雄性SD大鼠30只,随机分为3组:正常对照组(control group,C组)10只,予正常饮食;高脂模型组(model group,M组)10只、粪菌移植治疗组(treatment group,T组)10只,M组和T组均予高脂饮食。T组予粪菌液灌胃2 mL/次,隔日1次,粪菌液灌胃的前一天晚上及当天早上均予奥美拉唑镁肠溶片灌胃;C组及M组同时予奥美拉唑及生理盐水灌胃。喂养12周后实验结束,测定血中TG、ALT、AST水平;苏丹黑B染色观察肝脏病理学变化;取回肠末端肠组织行HE染色及扫描电镜观察肠黏膜结构变化。结果与M组大鼠相比,T组血清TG、ALT、AST水平降低,差异有统计学意义(均P0.05)。T组大鼠肝脏苏丹黑B染色可见肝细胞内脂肪沉积明显减少,脂肪变性程度较M组减轻。T组大鼠肠组织HE染色肠绒毛轻度水肿,排列较整齐、紧密。扫描电镜中可见T组大鼠肠绒毛形态较饱满,排列比较紧密,微绒毛之间的间隙变小。结论粪菌移植能改善肝功能,减轻肝脏脂肪变,降低肠道通透性,改善肠黏膜屏障功能。     

Biphasic assembly of the murine intestinal microbiota during early development

The birth canal provides mammals with a primary maternal inoculum, which develops into distinctive body site-specific microbial communities post-natally. We characterized the distal gut microbiota from birth to weaning in mice. One-day-old mice had colonic microbiota that resembled maternal vaginal communities, but at days 3 and 9 of age there was a substantial loss of intestinal bacterial diversity and dominance of Lactobacillus. By weaning (21 days), diverse intestinal bacteria had established, including strict anaerobes. Our results are consistent with vertical transmission of maternal microbiota and demonstrate a nonlinear ecological succession involving an early drop in bacterial diversity and shift in dominance from Streptococcus to Lactobacillus, followed by an increase in diversity of anaerobes, after the introduction of solid food. Mammalian newborns are born highly susceptible to colonization, and lactation may control microbiome assembly during early development.