Limosilactobacillus mucosae FZJTZ26M3 prevents NAFLD in mice through modulation of lipid metabolism and gut microbiota dysbiosis

Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease(NAFLD).The effects of two strains of Ltmosilactobacillus mucosae on NAFLD were investigated in this study.Fourweek-old male C57BL/6J mice were divided into 4 groups(n=8 per group,Control,Model,FZJTZ26M3,FGSYC17L3).L.mucosae FZJTZ26M3 reduced the mice 's body weight,liver weight,and adipose tissue weight after 12 weeks of therapy.According to serum analysis,total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol significantly decreased after L.mucosae FZJTZ26M3 intervention.Liver pathology showed that L.mucosae FZJTZ26M3 was effective to ameliorate lipid deposition in NAFLD mice.Additionally,the expression of the gene related to lipid metabolism in the liver and adipose tissue was analyzed,and the results indicated that L.mucosae FZJTZ26M3 could alleviate NAFLD by regulating lipid metabolism.Furthermore,the results of 16S rRNA gene sequencing revealed a drop in the relative abundance of Ruminococcaceae,which is linked to inflammation,but the relative abundance of a potential probiotic Akkermansia significantly increased after L.mucosae FZJTZ26M3 intervention.Generally,L.mucosae FZJTZ26M3 could be a candidate to prevent NAFLD.

创伤性脑损伤后肠黏膜细胞凋亡和c-fos基因表达

目的:研究创伤性脑损伤(TB I)后小肠黏膜细胞凋亡及c-fos基因表达,探讨肠黏膜上皮细胞凋亡在破坏肠黏膜屏障中的作用及c-fos基因表达与凋亡的关系。方法:雄性W istar大鼠,随机分为假手术(对照)组和脑创伤后3 h、12 h、24 h、72 h和7 d组,采用自由落体撞击致重型颅脑损伤。在各时相点取空肠近端,应用TUNEL法观测小肠黏膜细胞凋亡,应用免疫组化法观察c-fos基因的表达。结果:①凋亡细胞以肠黏膜上皮细胞为主;②脑损伤后3 h肠黏膜上皮即出现明显凋亡,凋亡细胞的数量以伤后72 h最多,分布于绒毛顶端,后延伸至绒毛中下部;③脑损伤后肠黏膜上皮细胞的c-fos基因表达逐渐增强,主要出现在上皮细胞、平滑肌细胞和淋巴细胞,伤后24 h、72h和7d的表达明显升高。结论:创伤性脑损伤可引起大鼠小肠黏膜细胞明显凋亡和c-fos基因的显著表达。

Characteristics of mucosa-associated gut microbiota during treatment in Crohn's disease

BACKGROUND The dysbiosis of the gut microbiome is evident in Crohn's disease(CD) compared with healthy controls(HC), although the alterations from active CD to remission after treatment are unclear.AIM To characterize the mucosa-associated gut microbiota in patients with CD before and after the induction therapy.METHODS The basic information was collected from the subjects and the CD activity index(CDAI) was calculated in patients. A 16S rRNA sequencing approach was applied to determine the structures of microbial communities in mucosal samples including the terminal ileal, ascending colon, descending colon and rectum. The composition and function of mucosa-associated gut microbiota were compared between samples from the same cohort of patients before and after treatment.Differential taxa were identified to calculate the microbial dysbiosis index(MDI)and the correlation between MDI and CDAI was analyzed using Pearson correlation test. Predictive functional profiling of microbial communities was obtained with PICRUSt.RESULTS There were no significant differences in microbial richness among the four anatomical sites in individuals. Compared to active disease, the alpha diversity of CD in remission was increased towards the level of HC compared to the active stage. The principal coordinate analysis revealed that samples of active CD were clearly separated from those in remission, which clustered close to HC. Sixty-five genera were identified as differentially abundant between active and quiescent CD, with a loss of Fusobacterium and a gain of potential beneficial bacteria including Lactobacillus, Akkermansia, Roseburia, Ruminococcus and Lachnospira after the induction of remission. The combination of these taxa into a MDI showed a positive correlation with clinical disease severity and a negative correlation with species richness. The increased capacity for the inferred pathways including Lipopolysaccharide biosynthesis and Lipopolysaccharide biosynthesis proteins in patients before treatment negatively correlated with the abundance of Roseburia,Ruminococcus and Lachnospira.CONCLUSION The dysbiosis of mucosa-associated microbiota was associated with the disease phenotype and may become a potential diagnostic tool for the recurrence of disease.

Effects of early postnatal gastric and colonic microbiota transplantation on piglet gut health

Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut.To secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period.Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(CON,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and diversity.Results Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single housing.However,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to CON(all P<0.05).CcFT also showed a lower ETEC prevalence on d 27(P<0.05).CMT showed a higher alpha diversity and a difference in beta diversity compared to CON(P<0.05).Growth and other paraclinical endpoints were similar across groups.Conclusion In conclusion,only CcFT reduced ETEC-related post-weaning diarrhea.However,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration,longer treatment periods,and better donor quality should be explored by future research to optimize the protective effects of transplantation.

Gastrointestinal mucosal immunity and COVID-19

As the gastrointestinal tract may also be a crucial entry or interaction site of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the role of the gut mucosal immune system as a first-line physical and immunological defense is critical.Furthermore,gastrointestinal involvement and symptoms in coronavirus disease 2019(COVID-19)patients have been linked to worse clinical outcomes.This review discusses recent data on the interactions between the virus and the immune cells and molecules in the mucosa during the infection.By carrying out appropriate investigations,the mucosal immune system role in SARS-CoV-2 infection in therapy and prevention can be established.In line with this,COVID-19 vaccines that stimulate mucosal immunity against the virus may have more advantages than the others.

Colorectal mucosal histamine release by mucosa oxygenation in comparison with other established clinical tests in patients with gastrointestinally mediated allergy

AIM： This study evaluated colorectal mucosal histamine release in response to blinded food challenge-positive and-negative food antigens as a new diagnostic procedure. METHODS： 19 patients suffering from gastrointestinally mediated allergy confirmed by blinded oral provocation were investigated on grounds of their case history, skin prick tests, serum IgE detection and colorectal mucosal histamine release by ex vivo mucosa oxygenation. Intact tissue particles were incubated/stimulated in an oxygenated culture with different food antigens for 30 min. Specimens challenged with anti-human immunoglobulin E and without any stimulus served as positive and negative controls, respectively. Mucosal histamine release （% of total biopsy histamine content） was considered successful （positive）, when the rate of histamine release from biopsies in response to antigens reached more than twice that of the spontaneous release. Histamine measurement was performed by radioimmunoassay. RESULTS： The median （range） of spontaneous histamine release from colorectal mucosa was found to be 3.2 （0.1%-25.8%） of the total biopsy histamine content. Food antigens tolerated by oral provocation did not elicit mast cell degranulation 3.4 （0.4%-20.7%, P=0.4）, while anti-IgE and causative food allergens induced a significant histamine release of 5.4 （1.1%-25.6%, P = 0.04） and 8.1 （1.5%-57.9%, P = 0.008）, respectively. 12 of 19 patients （63.1%） showed positive colorectal mucosal histamine release in accordance with the blinded oral challenge responding to the same antigen （s）, while the specificity of the functional histamine release to accurately recognise tolerated foodstuffs was found to be 78.6%. In comparison with the outcome of blinded food challenge tests, sensitivity and specificity of history （30.8% and 57.1%）, skin tests （47.4% and 78.6%） or antigen-specific serum IgE determinations （57.9% and 50%） were found to be of lower diagnostic accuracy in gastrointestinally mediated allergy. CONCLUSION： Functional testing of the reactivity of colorectal mucosa upon antigenic stimulation in patients with gastrointestinally mediated allergy is of higher diagnostic efficacy.

The immune modifying effects of amino acids on gut-associated lymphoid tissue

The intestine and the gut-associated lymphoid tissue（GALT） are essential components of whole body immune defense,protecting the body from foreign antigens and pathogens,while allowing tolerance to commensal bacteria and dietary antigens.The requirement for protein to support the immune system is well established.Less is known regarding the immune modifying properties of individual amino acids,particularly on the GALT.Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake,but the availability of specific dietary amino acids（in particular glutamine,glutamate,and arginine,and perhaps methionine,cysteine and threonine） are essential to optimizing the immune functions of the intestine and the proximal resident immune cells.These amino acids each have unique properties that include,maintaining the integrity,growth and function of the intestine,as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers,specific T cell functions,and the secretion of IgA by lamina propria cells.Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters.Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.

Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation

Short bowel syndrome （SBS） refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn＇s disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable. Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 （GLP-2） is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is atrophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor （GLP-2R） remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.

创伤性脑损伤后肠黏膜结构和屏障功能的变化

目的:探讨创伤性脑损伤后肠黏膜形态和屏障功能的变化,了解肠黏膜屏障功能障碍的发生时间及其严重程度。 方法:雄性Wistar大鼠随机分为无脑损伤的对照组和脑损伤后 3、12、24、72h和 7天组,每组 6只。应用组织病理和电镜观察肠黏膜结构的变化,通过测定血浆内毒素水平和肠黏膜通透性,以评价肠黏膜屏障功能。 结果:创伤性脑损伤后 3h即出现肠黏膜的病理改变,然后逐渐加重。与对照组相比,脑损伤后 3、12和 24h血浆内毒素水平明显升高,伤后 72h达到高峰,第 7天开始下降。血浆内毒素水平在伤后 3h和 72h出现两个峰值。脑损伤后肠黏膜通透性明显增加。 结论:创伤性脑损伤后 3h即可引起明显的肠黏膜结构和屏障功能损害,至伤后 72h达高峰,此损害可持续 7天以上。

顽固性便秘病人结肠黏膜菌群的变化特征

目的:阐释顽固性便秘病人结肠黏膜菌群的变化特征。方法:本研究分为顽固性便秘组(n=10)和对照组(n=6)。通过结肠镜活检获取乙状结肠黏膜标本,提取DNA,PCR扩增后行变性梯度凝胶电泳,应用分子生物学分析软件对菌群结构的相似性、主成分和多样性进行分析。结果:顽固性便秘病人结肠黏膜菌群有明显改变,与对照组比,顽固性便秘病人结肠黏膜菌群物种丰富度和香农多样性指数均显著降低(P<0.01)。结论:顽固性便秘病人结肠黏膜菌群紊乱,表现为结肠黏膜菌群多样性减少。

口服谷氨酰胺对烫伤大鼠小肠功能和结构的影响

测定烫伤大鼠早期口服谷氨酰胺（Ｇｌｎ）后血和组织中的游离氨基酸（ＦＡＡ）、二胺氧化酶（ＤＡＯ）、谷胱甘肽（ＧＨＳ）、肿瘤坏死因子（ＴＮＦ）和血浆内毒素（ＬＰＳ）的含量。结果表明，烫伤后１０ｈ、２ｄ、５ｄ、和８ｄ小肠ＤＡＯ水平降低，血浆ＤＡＯ升高；标准饲料（Ｃ）组血浆Ｇｌｎ在伤后２ｄ和５ｄ降低；Ｇｌｎ饲料（Ｇ）组各时点均增加，１０ｈ和８ｄ增加显著；Ｇｌｎ＋精氨酸（Ｇ＋Ａ）组在２ｄ降低。Ｃ组血浆丙氨酸、精氨酸和血氨较其它２组低。ＬＰＳ水平增高，但Ｃ与Ｇ组比较无统计学差异。病理检查见Ｃ组在伤后１０ｈ、５ｄ和８ｄ小肠绒毛萎缩变短，固有层慢性炎性细胞增多，肠壁变薄，Ｃ组和Ｇ＋Ａ组小肠粘膜厚度接近正常。提示口服Ｇｌｎ可能对烫伤大鼠小肠粘膜结构和功能有保护作用。

肠黏膜免疫屏障及其保护措施

肠黏膜是构成动物体内与外界环境之间最大的接触表面,是易受病原体定植和入侵的最常见部位。肠黏膜免疫屏障作为保护动物机体免受外来病原微生物侵扰的重要防线,可在抗原的刺激下利用免疫细胞和免疫相关物质产生特异性免疫应答,同时可对无害抗原下调免疫反应或产生免疫耐受。研究肠黏膜免疫屏障功能作用的机制并通过人为保护性措施来预防和修复肠黏膜免疫功能损伤对于动物机体免疫屏障功能的正常发挥和生产实践具有重要意义。

断奶日龄对仔猪肠道黏膜水解酶及其上皮间淋巴细胞和杯状细胞数的影响

本研究选用了12窝0～56天仔猪,随机等分成17、21、28、35天断奶4个处理组(处理1、2、3和4),每处理3个重复,每重复1窝仔猪。试验期间,实行三阶段饲养,7天开始补饲,7～28、29～42、42～56天分别采食日粮I、II、III。处理1、2、3、4分别于18、22、28、36,22、28、36、43,28、36、43、50和18、22、28、36、43、50天剖杀,每次每个重复1头,共计54头。剖杀取得的十二指肠、空肠前段、空肠后段和回肠样品用于测定仔猪肠黏膜水解酶、糖原和上皮间淋巴细胞(IEL)、杯状细胞(GC)数。结果表明:处理1、2仔猪小肠黏膜碱性磷酸酶活性低于处理3、4同周龄仔猪;随着周龄增加,仔猪小肠黏膜α-醋酸萘酯酶活性增强,至5周龄时达到高峰;断奶越早,仔猪十二指肠腺及肠腺糖原阳性反应较弱。仔猪小肠各段IELs处理3显著高于其它3组(P<0.05),而处理2则显著低于其它3组(P<0.05)。断奶越早、日龄越小的仔猪肠GCs显著升高(P<0.05)。

肠道菌群与脑-肠轴功能相互影响的研究进展

人体肠道内的菌群参与了许多生理功能的维持和疾病的发生。作为大脑和胃肠道功能相互调节的重要桥梁,脑-肠轴功能的正常发挥是肠道菌群维持稳定的条件。脑-肠轴紊乱可激活肠黏膜免疫,对肠道菌群产生影响,使菌群结构发生改变。反之,肠道菌群结构改变亦会影响神经系统发育,导致脑-肠轴功能紊乱,其中迷走神经和血清代谢物质在脑-肠轴功能的调节中发挥重要作用。本文就肠道菌群与脑-肠轴功能相互影响的研究进展作一综述。

正肝汤对肝硬化大鼠内毒素血症以及肠道细菌移位的影响

目的:探讨正肝汤对肝硬化大鼠内毒素血症以及肠道细菌移位的影响。方法:30只SD大鼠随机分为正常组、模型组和正肝汤组,每组各30只。制备四氯化碳肝硬化大鼠模型,正肝汤组大鼠予正肝汤(1.5 g/100g/d)灌胃干预。对肝及小肠组织进行苏木素-伊红染色,采用鲎试剂法检测血浆内毒素水平,摘取肠系膜淋巴结以及适量肝脾组织置血平板培养进行肠道细菌移位检测。结果:与正常组相比较,模型组大鼠的肝组织中胶原纤维广泛增生,纤维间隔相互连接,徦小叶形成,肠黏膜充血、水肿,黏膜下炎性细胞浸润增多,绒毛萎缩、脱落。正肝汤组大鼠的肝脏胶原增生程度分级以及肠黏膜损伤指数(Ogura评分)与模型组相比较显著下降,均P<0.05,有统计学差异。正常组大鼠的内毒素阳性率和肠道细菌移位阳性率均为0%,肝硬化模型组的内毒素阳性率和肠道细菌移位阳性率分别为55.6%和66.7%,与正常组相比较均显著增高,均P<0.01。正肝汤组的内毒素阳性率和肠道细菌移位阳性率分别为10%和0%,与模型组相比较均显著降低,分别P<0.05和P<0.01。结论:正肝汤能显著减轻肝硬化大鼠肝脏中的胶原沉积以及肠黏膜损伤,改善内毒素血症以及肠道细菌移位。

肠道必需氨基酸代谢及其功能的研究进展

在肠道代谢过程中,食物必需氨基酸可不同程度地被肠道组织利用。这些必需氨基酸,除了用于合成肠黏膜蛋白质外,还可通过不同途径在肠上皮细胞内代谢。它们不仅是小肠黏膜的能量物质,同时还参与肠道内氨基酸、谷胱甘肽和多胺等多种生物活性物质的合成,对维持肠黏膜完整性和肠道功能有重要意义,对整个机体的代谢产生重要的影响。

胃粘膜组织激素与胃癌、消化性溃疡的相关性研究

目的 研究胃泌素、胃动素、生长抑素及胰高血糖素等胃肠激素在胃癌癌组织及消化性溃疡的含量变化及它们之间的相关性。方法 内镜及活检确诊的慢性浅表性胃炎 (CSG) 2 4例 ,十二指肠球部溃疡 (DU) 2 0例 ,胃溃疡 (GU) 18例 ,胃癌 (GC) 15例 ,胃镜下取胃窦粘膜及胃癌癌组织 ,用RLA法测定胃泌素、胃动素、生长抑素及胰高血糖素的含量。结果 胃癌癌组织中 ,胃泌素、胃动素及胰高血糖素的含量分别为 168 9pg/mL± 62 5pg/mL、43 5 5pg/mL± 97 1pg/mL、12 3 4pg/mL± 41 3pg/mL ,明显高于DU(87 3pg/mL± 2 0 4pg/mL、3 72 2pg/mL± 86 9pg/mL、84 8pg/mL± 2 3 6pg/mL)、GU(92 5pg/mL± 2 6 3pg/mL、3 84 6pg/mL± 78 6pg/mL、64 9pg/mL± 18 2pg/mL)、及CSG(76 9pg/mL± 3 0 6pg/mL、2 86 7pg/mL± 64 3pg/mL、3 6 7pg/mL、14 3pg/mL)组 (P <0 0 1) ,生长抑素的含量 2 8 7pg/mL± 16 3pg/mL却显著低于DU(78 4pg/mL± 3 2 3pg/mL)、GU(86 9pg/mL± 2 8 8pg/mL)及CSG(4 6 8pg/mL± 13 4pg/mL)组 (P <0 0 1)。同时亦发现上述激素在GU及DU组的含量亦明显高于CSG组 (P <0 0 1)。结论 胃泌素、胃动素、生长抑素、胰高血糖素含量的变化可能参与了胃癌的发生、发展 ,并与溃疡的形成相关。

肠道微生态系统与肠黏膜免疫关系研究进展

肠道微生态系统参与肠黏膜免疫系统的发育,促进肠黏膜分泌型免疫球蛋白A(secreted IgA,sIgA)的合成,并与肠黏膜免疫细胞相互调节,是维持肠道稳态的重要机制,在炎症性肠病、肠易激综合征、小儿过敏性疾病等疾患的发生发展中发挥重要的作用。文中对肠道微生态系统与肠黏膜免疫功能关系的进展作一综述。

生物活性肽对肠黏膜免疫调节作用的研究进展

大量研究已证实生物活性肽是一类对机体有许多重要生理功能的物质,对拥有巨大表面积的肠黏膜有着重要的免疫调节作用。本文首先概括生物活性肽的研究现状;在从肠黏膜系统组成及其免疫机制的角度,结合前期的研究工作,就生物活性肽对SIgA、Th细胞及其细胞因子以及免疫信号途径影响的相关研究进行介绍。同时根据国外学者近期研究的成果,提出研究生物活性肽与机体免疫作用关系的发展趋势。