不同途径补充谷氨酰胺对大鼠肠粘膜和通透性的影响

目的比较大鼠手术化疗时,普通肠外、肠内营养与补充谷氨酰胺的肠外、肠内营养对肠道功能的影响.方法雄性Wistar大鼠60只,随机分为6组(n=10)Chow 1组,普通饲料加中心静脉插管;PN组,普通肠外营养;PN+G组,肠外营养加谷氨酰胺;Chow 2组,普通饲料加胃造瘘;EN组,普通肠内营养;EN+G组,肠内营养加谷氨酰胺.Chow组给普通饲料,肠外和肠内营养组所给营养液均为等氮2.5 g N@kg-1@d-1、等热卡1 046 kJ@kg-1@d-1(250 kcal@kg-1@d-1),氮热卡比值1100.4组营养支持大鼠在术后第4天,按75 mg@kg-1体重腹腔注射5-Fu.结果(1)体重术后第8天时,以PN组下降最显著(-14.8±7.6)g(P＜0.05);EN组其次(-6.6±2.2)g(P＜0.05);PN+G组略有下降(-1.1±0.2)g,但无统计学差异;EN+G组体重则有所增加(2.7±4.2)g.(2)谷氨酰胺浓度与Chow组比较,PN组和EN组血浆和肌肉的谷氨酰胺浓度显著下降,而PN+G组和EN+G组谷氨酰胺浓度增高.(3)细菌移位PN组和EN组细菌移位阳性率分别为80%和70%(P＜0.05);PN+G组、EN+G组和Chow组分别为30%、30%和20%,3组间比较无显著差异.(4)肠道粘膜通透性与手术后化疗前比较,PN组和EN组的通透性增加(P＜0.05),而PN+G组和EN+G组的通透性变化不大,与Chow组比较无显著性差异.(5)肠粘膜形态术后第8天时,PN组和EN组空肠和结肠粘膜厚度和绒毛高度显著低于Chow组(P＜0.01),PN+G组和EN+G组与Chow组相似,EN+G组的绒毛高度和粘膜厚度优于PN+G组.结论补充谷氨酰胺的肠外、肠内营养与普通肠外、肠内营养比较,可减少肠道通透性增高和细菌移位、减少肠粘膜损伤,并能增加血浆、肌肉和小肠谷氨酰胺水平,肠内营养补充谷氨酰胺对肠道功能的影响优于肠外营养补充谷氨酰胺.     

肝脏疾病与肠黏膜屏障

肝脏疾病可以引起肠黏膜屏障受损，进而肠道内细菌发生移位，导致菌血症和内毒素血症，并进一步加重肝损伤。     

The Role of L‐Arginine and Inducible Nitric Oxide Synthase in Intestinal Permeability and Bacterial Translocation

Background: Arginine has been shown to have several immunological and trophic properties in stressful diseases. Its metabolites, nitric oxide (NO) and polyamines, are related to arginine's effects. Thus, the aim of this study was to determine the effects of the NO donor L‐arginine and the role of inducible NO synthase (iNOS) on intestinal permeability and bacterial translocation in a model of intestinal obstruction (IO) induced by a simple knot in the terminal ileum. Material and Methods: Male C57BL6/J wild‐type (WT) and iNOS knockout (iNOS–/–) mice were randomized into 6 groups: Sham and Sham–/– (standard chow), IO and IO–/– (standard chow +IO), and Arg and Arg–/– (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chows, IO was induced and intestinal permeability and bacterial translocation were evaluated. The small intestine and its contents were harvested for histopathological and morphometric analysis and the determination of polyamine concentration. Results: Pretreatment with arginine maintained intestinal permeability (P > .05; Arg and Arg–/– groups vs Sham and Sham–/– groups), increased polyamine concentration in intestinal content (P < .05; Arg vs IO group), and decreased bacterial translocation in WT animals (Arg group vs IO and IO–/– groups). Absence of iNOS also presented a protective effect on permeability but not on bacterial translocation. Conclusion: Arginine supplementation and synthesis of NO by iNOS are important factors in decreasing bacterial translocation. However, when intestinal permeability was considered, NO had a detrimental role.     

谷氨酰胺双肽改善烧伤患者切痂术后肠粘膜通透性、内毒素血症和预后的研究

目的探讨静脉补充谷氨酰胺双肽对重度烧伤患者术后肠粘膜通透性及血浆内毒素浓度的影响。方法30例烧伤总面积30%～50%、Ⅲ°面积15%～25%的患者随机加入对照组和研究组,每组15例。两组患者手术后接受静脉营养治疗,研究组接受静脉谷氨酰胺双肽0.5g·kg-1d-1,对照组仅以平衡氨基酸提供氮源。两组营养供应等氮等热卡。检测术前第1天、术后第1天、术后第12天,血浆谷氨酰胺浓度、尿乳果糖和甘露醇排出率比率(L/M)、血浆内毒素浓度,检查术后12天植皮成活率、创面愈合时间及治疗费用,数据用SPSS11.0进行统计分析。结果两组血浆谷氨酰胺浓度术前第1天均显著低于正常值,对照组(390.6±43.7)μmol/L,研究组(386.7±51.8)μmol/L,正常值(659.5±35)μmol/L;术后第1天,对照组血浆谷氨酰胺浓度显著下降,但研究组上升,两组差异显著(P=0.000);术后第12天,研究组接近正常值,高于对照组,对照组(397.8±38.7)μmol/L,研究组(532.1±48.9)μmol/L(P=0.000)。两组L/M值术前第1天显著高于正常值,对照组0.103±0.050,研究组0.112±0.045,正常值0.022±0.0016;术后第1天两组L/M值均比术前升高,但研究组显著低于对照组,对照组0.175±0.022,研究组0.138±0.039(P=0.003);术后第12天,研究组恢复正常,优于对照组。两组血浆内毒素浓     

肠黏膜血流改变在创伤性脑损伤大鼠肠黏膜屏障应激性变化中的作用

目的探讨肠黏膜血流改变在创伤性脑损伤大鼠肠黏膜屏障应激性变化机制中的作用。方法雄性Wistar大鼠64只，随机分为创伤性脑损伤组和假手术组，2组大鼠分别按术后6、12、24和48小时时相点分为4个亚组（n=8），测定肠黏膜血流量，光镜和透射电镜下观察肠黏膜组织形态学变化。结果创伤性脑损伤组各时相点的肠黏膜血流量均低于假手术组（P〈0．05）；光镜下创伤性脑损伤组肠黏膜上皮细胞受损，电镜下可见肠黏膜细胞间紧密连接较假手术组增宽。结论创伤性脑损伤后早期肠黏膜屏障即已受损，而肠黏膜血流量的下降是导致这一病理生理变化的重要因素之一。     

Partial Enteral Nutrition Preserves Elements of Gut Barrier Function,Including Innate Immunity,Intestinal Alkaline Phosphatase (IAP) Level,and Intestinal Microbiota in Mice

Lack of enteral nutrition (EN) during parenteral nutrition (PN) leads to higher incidence of infection because of gut barrier dysfunction. However, the effects of partial EN on intestina linnate immunity, intestinal alkaline phosphatase (IAP) and microbiota remain unclear. The mice were randomized into six groups to receive either standard chow or isocaloric and isonitrogenous nutritional support with variable partial EN to PN ratios. Five days later, the mice were sacrificed and tissue samples were collected. Bacterial translocation, the levels of lysozyme, mucin 2 (MUC2), and IAP were analyzed. The composition of intestinal microbiota was analyzed by 16S rRNA pyrosequencing. Compared with chow, total parenteral nutrition (TPN) resulted in a dysfunctional mucosal barrier, as evidenced by increased bacterial translocation (p < 0.05), loss of lysozyme, MUC2, and IAP, and changes in the gut microbiota (p < 0.001). Administration of 20% EN supplemented with PN significantly increased the concentrations of lysozyme, MUC2, IAP, and the mRNA levels of lysozyme and MUC2 (p < 0.001). The percentages of Bacteroidetes and Tenericutes were significantly lower in the 20% EN group than in the TPN group (p < 0.001). These changes were accompanied by maintained barrier function in bacterial culture (p < 0.05). Supplementation of PN with 20% EN preserves gut barrier function, by way of maintaining innate immunity, IAP and intestinal microbiota.     

Intestinal Barrier Permeability in Obese Individuals with or without Metabolic Syndrome: A Systematic Review

Altered intestinal barrier permeability has been associated with obesity and its metabolic and inflammatory complications in animal models. The purpose of this systematic review is to assess the evidence regarding the association between obesity with or without Metabolic Syndrome (MetS) and alteration of the intestinal barrier permeability in humans. A systematic search of the studies published up until April 2022 in Latin America & Caribbean Health Sciences Literature (LILACS), PubMed, Scopus, Embase, and ScienceDirect databases was conducted. The methodological quality of the studies was assessed using the Newcastle–Ottawa scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) checklist. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the quality of the evidence. Eight studies were included and classified as moderate to high quality. Alteration of intestinal barrier permeability was evaluated by zonulin, lactulose/mannitol, sucralose, sucrose, lactulose/L-rhamnose, and sucralose/erythritol. Impaired intestinal barrier permeability measured by serum and plasma zonulin concentration was positively associated with obesity with MetS. Nonetheless, the GRADE assessment indicated a very low to low level of evidence for the outcomes. Thus, clear evidence about the relationship between alteration of human intestinal barrier permeability, obesity, and MetS was not found.     

Gastrointestinal Digestion of a Grape Pomace Extract: Impact on Intestinal Barrier Permeability and Interaction with Gut Microbiome

Grape pomace (GP) is a winemaking by-product rich in polyphenols and fibre. Supplementation with GP extracts has shown potential benefits against oxidative stress- and inflammation-related pathologies. As a new nutritional target, this paper explores the impact of the ingestion of a grape pomace extract on intestinal barrier functionality. A GP extract was sequentially subjected to gastrointestinal and colonic digestion using the dynamic gastrointestinal simulator (simgi^®). This generated two simulated fluids: intestinal-digested extract (IDE) and colonic-digested extract (CDE). The effects of these two fluids on paracellular permeability and the expression of tight junction (TJ) proteins (i.e., zonula occludens-1 (ZO-1) and occludin) were assessed in Caco-2-cell monolayers grown in Transwell^® inserts. The IDE fluid significantly (p < 0.001) reduced the paracellular transport of FITC-dextran with respect to the control, whereas no significant differences (p > 0.05) were found for CDE, which could be due, at least partially, to the pro-leaky effect of the colonic digestion medium. Accordant slight increases in the mRNA levels of both ZO-1 and occludin were observed for IDE, but without statistical significance. Additionally, the colonic fermentation of the GP extract promoted the production of short-chain fatty acids (SCFA) and phenolic metabolites and led to changes in the relative abundance of some bacteria that might affect paracellular permeability. Overall, this paper reports first trends about the effects of grape pomace extracts on intestinal permeability that would require further confirmation in future experiments.     

三七总皂苷与谷氨酰胺对大鼠肠屏障保护作用的比较

目的比较大鼠肠缺血再灌注损伤时,三七总皂苷(PNS)与谷氨酰胺(Gln)的肠屏障保护作用。方法将60只健康SD大鼠随机分为以下4组:(1)PNS组(n=20),给予PNS胃内灌服,每日3次,每次50mg/kg,共3天;(2)Gln组(n=20),给予Gln胃内灌服,每日3次,每次1g/kg,共3天;(3)单纯手术对照组(n=10),除不夹闭肠系膜上动脉(SMA),其余操作同模型对照组;(4)模型对照组(n=10)。均在最后一次给药2小时后进行手术,夹闭SMA造成肠缺血,1小时后恢复SMA血流,再灌注3小时后分别观察血浆内毒素水平,肝、脾和肠系膜淋巴结的细菌移位率及小肠组织病理学改变。结果(1)模型对照组、PNS组和Gln组大鼠肠道细菌移位率分别为73.33%、45.00%和46.67%,明显高于单纯手术对照组的3.33%(P均<0.01);而模型对照组的细菌移位率也明显高于PNS组和Gln组(P均<0.05);PNS组与Gln组之间差异无显著性(P>0.05)。(2)模型对照组、PNS组和Gln组大鼠血浆内毒素水平分别为(0.553±0.039)、(0.318±0.061)和(0.336±0.05)EU/ml,明显高于单纯手术对照组的(0.152±0.052)EU/ml(P均<0.01);而模型对照组的血浆内毒素水平也明显高于PNS组和Gln组(P均<0.05);PNS组与Gln组之间差异无显著性(P>0.05)。(3)电镜下可见模型对照组损伤较严重,PNS组与Gln组损伤较轻。光镜下chiu分级,PNS组与Gln组相比差异无显著性(P>0.05),但PNS组及Gln组与模型对照组相比损伤均明显减轻(P均<0.01)。结论PNS和Gln胃内灌服给药对缺血再灌注3小时的大鼠肠黏膜屏障具有一定保护作用,二者差异无显著性。     

谷氨酰胺对放射损伤大鼠肠粘膜组织结构及其DNA和蛋白含量的影响

目的观察谷氨酰胺对放射损伤大鼠肠粘膜组织结构及其肠粘膜上皮细胞DNA与蛋白含量的影响。方法体重(159.4±9.21)g的雄性Wistar大鼠30只,随机分为对照组(Control组)、添加谷氨酰胺照射组( GLN组)、未添加谷氨酰胺照射组(-GLN组),每组10只。以不同饲料配方喂养至第15天, GLN组和-GLN组大鼠给予9.0Gry的60Coγ全身照射。继续喂养至第20天处死全部动物,取材观察空肠粘膜光镜和电镜组织结构形态,并进行肠粘膜上皮细胞DNA、蛋白质含量的测定。结果-GLN组肠粘膜变薄、萎缩,扫描电镜可见绒毛顶端溃疡明显, GLN组肠粘膜病理改变较轻。3组肠粘膜上皮细胞DNA含量均无显著性差异,-GLN组较Control组蛋白质含量明显降低(P<0.01)。结论谷氨酰胺可减轻肠粘膜结构的急性放射损害,并对减少肠粘膜上皮细胞内蛋白质的丢失可能有积极作用。     

Effects of Enteral Nutrition on the Barrier Function of the Intestinal Mucosa and Dopamine Receptor Expression in Rats With Traumatic Brain Injury

Background: Impaired intestinal mucosal barrier (IMB) function is common in traumatic brain injury (TBI), but dopamine receptors (DRs) change in intestinal mucosa after TBI, and effects of enteral nutrition (EN) and supplements on IMB function remain unclear. Our purpose was to study the effects of EN and supplements on intestinal mucosal permeability (IMPB) and the expression of DRs DRD1 and DRD2 in the intestinal mucosa of rats with TBI. Methods: Forty‐eight rats were divided into 8 groups; control, animals with TBI, dopamine group, animals with TBI treated with dopamine antagonist, EN alone, or EN combined with glutamine, probiotics, or a combination of probiotics and glutamine daily after TBI. Results: The IMPB was improved in the glutamine, probiotics, and combination groups. Including probiotics improved IMPB more than adding glutamine, and bacterial translocation in the intestines after TBI was reduced in the probiotics and combination groups (all Ps < .01). TBI led to elevated DRD1 and DRD2 mRNA and protein levels, which were reduced in the DA antagonist, glutamine, probiotics, and combination groups. DRD2 mRNA and protein levels in the probiotics and combination groups were decreased more than in the DA antagonist group (all Ps < .01). The increased IMPB after TBI correlated with increased DRD1 and DRD2 levels in the rat intestinal mucosa. Conclusion: EN supplemented with probiotics or combining glutamine and probiotics lowers the increased IMPB, bacterial translocation, and DRD1 and DRD2 mRNA and protein expression in rat intestinal mucosa caused by TBI.     

急性白血病患者实验室证实的黏膜屏障损伤所致血流感染发生机制与研究进展

白血病已成为人类健康的重要威胁,感染并发症是临床白血病顺利治疗的主要障碍。白血病本身肿瘤特点和高强度化学治疗导致肠道屏障完整性损伤,肠道菌群易位是血流感染(BSI)的重要原因。实验室证实的黏膜屏障损伤所致血流感染(MBI-LCBI)是急性白血病患者BSI的重要组成,但相关研究非常有限。本文通过文献分析,综述黏膜屏障损伤、细菌易位,以及MBI-LCBI定义、诊断、流行情况, 分析肠道微生态调节黏膜屏障完整性及MBI-LCBI的作用机制,以期为化学治疗介导黏膜炎及MBI-LCBI的防治及管理提供理论基础。     

谷氨酰胺和精氨酸联合应用对化疗后大鼠肠屏障的保护作用

目的 观察谷氨酰胺(Gln)和精氨酸(Arg)联合应用对腹腔注射氟尿嘧啶(5-FU)化疗后大鼠肠屏障的保护作用.方法 将40只接受5-FU化疗的健康雄性SD大鼠随机分为单纯肠内营养组、Gln组(肠内营养+Gln)、Arg组(肠内营养+Arg)和Arg+Gln组(肠内营养+Arg+Gln)4组,每组10只.在化疗前后测定各组大鼠体重、尿乳果糖/甘露醇比值(L/M),并在第8天测定门静脉血内毒素,进行门静脉血和淋巴结培养并测定回肠绒毛高度和回、结肠肠壁厚度.结果 除单纯肠内营养组外,其余各组大鼠体重均明显增加(P<0.05);Arg+Gln组体重增加幅度明显低于Gln组(P=0.002),与Arg组差异无统计学意义(P>0.05).化疗后各组L/M值均明显增加(P<0.05);单纯肠内营养组的增加幅度明显高于其他各组(P=0.000),其余各组间差异无统计学意义(P>0.05).单纯肠内营养组的血内毒素水平明显高于其他各组(P=0.000);Gln组明显低于Arg组(P=0.035);Arg+Gln组明显高于Gln组(P=0.000),但与Arg组差异无统计学意义(P=0.109).单纯肠内营养组的回肠绒毛高度和回肠壁厚度明显低于其他各组(P=0.000),结肠壁厚度明显低于Arg组和Arg+Gln组(P=0.000),与Gln组差异无统计学意义(P=0.058);Gln组的回肠壁厚度(P=0.040)和结肠壁厚度(P=0.010)明显高于Arg组,回肠绒毛高度与Arg组差异无统计学意义(P=0.286);Gln组回肠壁厚度明显高于Arg+Gln组(P=0.028),结肠壁厚度(P=0.462)和回肠绒毛高度(P=0.190)与Arg+Gln组差异无统计学意义;Arg组结肠壁厚度明显低于Arg+Gln组(P=0.010),回肠绒毛高度(P=0.803)及回肠壁厚度(P=0.059)与Ag+Gln组差异无统计学意义.各组间门静脉血和淋巴结细菌培养结果差异无统计学意义(P>0.05).结论 Arg、Gln对腹腔注射5-FU化疗后大鼠肠屏障功能具有保 护作用,Gln的保护作用略优于Arg,两者没有明显的协同作用.     

谷氨酰胺和重组人生长激素对门静脉高压症患者术后肠黏膜屏障功能的影响

目的研究单独或联合应用谷氨酰胺（Gln）和重组人生长激素（rhGH）对门静脉高压症患者术后肠黏膜屏障功能的影响。方法将29例肝硬化门静脉高压症接受手术治疗的患者随机分为4组：Gln组（n=6）、rhGH组（n=8）、Gln＋rhGH组（n=7）和对照组（n=8）。术后3天开始进行等氮、等热量的全胃肠外营养（TPN）支持，持续7天。对患者手术前、后的尿乳果糖／甘露醇（L／M）、十二指肠降段黏膜绒毛高度及陷窝深度进行测定。结果Gln＋rhGH组L／M升高的幅度显著小于对照组（P〈0．05），Gln和rhGH组与对照组比较差异无显著性。Gln＋rhGH组肠黏膜绒毛高度和陷窝深度均大于对照组（P〈0．05），Gln和rhGH组与对照组比较差异无显著性（P〉0．05）。Gln＋rhGH组术后绒毛高度及陷窝深度均显著大于术前（P〈0．05）；对照组术后绒毛高度小于术前（P〈0．05），陷窝深度差异无显著性（P〉0．05）；Gln和rhGH组手术前、后绒毛高度及陷窝深度差异无显著性（P〉0．05）。结论联合应用Gln和rhGH能降低门静脉高压症患者术后肠壁通透性并维护肠黏膜形态学完整性，单独应用Gln或rhGH无此作用。     

肠脂肪酸结合蛋白与肝硬化患者细菌感染和不良预后的相关性研究

目的 评估肠脂肪酸结合蛋白(I-FABP)对肝硬化患者预后预测的价值。方法 采用前瞻性研究方法,连续收集某院2020年9月—2022年5月住院治疗的肝硬化患者,根据Child-Pugh评分对患者进行分层,随访时间12个月,以评估其生存及细菌感染情况。采用酶联免疫吸附试验(ELISA)法测定患者入院血清I-FABP水平。两变量间相关性应用Spearman相关分析。多因素Cox回归模型预测随访期间细菌感染和死亡的危险因素。时间依赖性ROC曲线评估I-FABP对肝硬化相关死亡的预测性能。结果 共纳入131例肝硬化患者,随访期间有45例患者因细菌感染或感染发展住院治疗。感染住院中位时间为115(42, 251)d,平均住院时间15 d。最常见的感染是自发性细菌性腹膜炎(SBP),占20.6%(27例)。I-FABP与血清IL-6(r=0.270,P<0.001)和MELD评分(r=0.364,P<0.001)相关,并随疾病严重程度增加而升高(Child-Pugh A级=1.18μg/L,Child-Pugh B级=1.51μg/L和C级=2.29μg/L)。随访期间有45例(34....     

Human Milk Oligosaccharides and Lactose Differentially Affect Infant Gut Microbiota and Intestinal Barrier In Vitro

Background: The infant gut microbiota establishes during a critical window of opportunity when metabolic and immune functions are highly susceptible to environmental changes, such as diet. Human milk oligosaccharides (HMOs) for instance are suggested to be beneficial for infant health and gut microbiota. Infant formulas supplemented with the HMOs 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT) reduce infant morbidity and medication use and promote beneficial bacteria in the infant gut ecosystem. To further improve infant formula and achieve closer proximity to human milk composition, more complex HMO mixtures could be added. However, we currently lack knowledge about their effects on infants’ gut ecosystems. Method: We assessed the effect of lactose, 2′-FL, 2′-FL + LNnT, and a mixture of six HMOs (HMO6: consisting of 2′-FL, LNnT, difucosyllactose, lacto-N-tetraose, 3′- and 6′-sialyllactose) on infant gut microbiota and intestinal barrier integrity using a combination of in vitro models to mimic the microbial ecosystem (baby M-SHIME^®) and the intestinal epithelium (Caco-2/HT29-MTX co-culture). Results: All the tested products had bifidogenic potential and increased SCFA levels; however, only the HMOs’ fermented media protected against inflammatory intestinal barrier disruption. 2′-FL/LNnT and HMO6 promoted the highest diversification of OTUs within the Bifidobactericeae family, whereas beneficial butyrate-producers were specifically enriched by HMO6. Conclusion: These results suggest that increased complexity in HMO mixture composition may benefit the infant gut ecosystem, promoting different bifidobacterial communities and protecting the gut barrier against pro-inflammatory imbalances.     

A. muciniphila Supplementation in Mice during Pregnancy and Lactation Affects the Maternal Intestinal Microenvironment

During pregnancy and lactation, considerable factors that affect the maternal microbiome are associated with the advancement of numerous diseases, which can potentially affect offspring health. Probiotics have shown potential for the maintenance of microbiota homeostasis of mothers in this period. The specific objective of this study was to investigate whether the application of Akkermansia muciniphila (A. muciniphila) during pregnancy and lactation impacts maternal and offspring health. Here we show that dams fed with A. muciniphila is safe, enhances the intestinal barrier and alters gut microbiota composition and diversity at the end of lactation, including the significant enrichment of A. muciniphila and Ruminococcus_1 in offspring from probiotic-fed dams. However, compared with the control group, the fecal metabolites of the A. muciniphila group only changed slightly. Additionally, A. muciniphila supplementation did not significantly increase the abundance of A. muciniphila in the fecal microbiota of offspring mice. Compared with the control group, the fecal metabolic profile of three-week-old offspring of mice fed with A. muciniphila were significantly changed, containing the D-glutamine and D-glutamate metabolism pathways. These results provided evidence that A. muciniphila supplementation in mice during pregnancy and lactation is safe and seemed to have a more beneficial effect on dams. In the future, using probiotics to regulate maternal microbiomes during pregnancy and lactation could be shown to have a more lasting and beneficial effect.     

Nutrition Status and Intestinal Permeability in Patients Eligible for Liver Transplantation

Background: Increased intestinal permeability has been reported in multiple studies of cirrhotic patients, although specific factors associated with this finding have not been fully elucidated. Thus, the aim of this study was to investigate whether there was an association between nutrition status measured by different methods and intestinal permeability in cirrhotic patients who were candidates for liver transplantation. Materials and Methods: The study group comprised 18 cirrhotic patients and 15 healthy controls. Patients' nutrition status was evaluated by Subjective Global Assessment (SGA), anthropometry, dynamometry, and phase angle, which was determined by bioelectrical impedance analysis. Intestinal permeability was assessed by the lactulose/mannitol test. Results: The prevalence of malnutrition showed wide variance between different assessment methods (5.5%–77.8%). Intestinal permeability was significantly higher in cirrhotic patients than in healthy controls. In relation to nutrition status, intestinal permeability and phase angle did not differ significantly between patients who were considered well nourished (median intestinal permeability, 0.010 [range, 0.001–0.198]; median phase angle, 6.0 [range, 4.2–6.9]) and malnourished patients (intestinal permeability, 0.032 [range, 0.002–0.079]; phase angle, 4.8 [range, 2.2–6.1]) by SGA. In addition, no correlation was found between nutrition diagnosis as assessed by different methods, patient age, liver disease severity scores, and laboratory measurements with intestinal permeability. Conclusion: Although intestinal permeability was increased in cirrhotic patients, this finding was not associated with nutrition status.     

Activation of Free Fatty Acid Receptor 4 Affects Intestinal Inflammation and Improves Colon Permeability in Mice

Diet is considered an important trigger in inflammatory bowel diseases (IBD), as feeding habits can affect intestinal permeability and clearance of bacterial antigens, consequently influencing the immune system. Free fatty acid receptors (FFARs), expressed on the intestinal epithelial cells, belong to the family of luminal-facing receptors that are responsive to nutrients. The objective of this study was to characterize the anti-inflammatory activity and the effect on intestinal barrier function of synthetic FFAR agonists in mouse models of colitis. Therapeutic activity of GW9508 (FFAR1 agonist), 4-CMTB (FFAR2 agonist), {"type":"entrez-nucleotide","attrs":{"text":"AR420626","term_id":"40175736"}}AR420626 (FFAR3 agonist), and GSK137647 (FFAR4 agonist) was investigated in two models of semi-chronic colitis: induced by trinitrobenzenesulfonic acid (TNBS), mimicking Crohn’s disease, as well as induced by dextran sulfate sodium (DSS), which recapitulates ulcerative colitis in humans. Moreover, we assessed the influence of FFARs agonists on epithelial ion transport and measured the ion flow stimulated by forskolin and veratridine. Administration of FFAR4 agonist GSK137647 attenuated both TNBS-induced and DSS-induced colitis in mice, as indicated by macroscopic parameters and myeloperoxidase activity. The action of FFAR4 agonist GSK137647 was significantly blocked by pretreatment with selective FFAR4 antagonist AH7614. Moreover, FFAR1 and FFAR4 agonists reversed the increase in the colon permeability caused by inflammation. FFAR4 restored the tight junction genes expression in mouse colon. This is the first evaluation of the anti-inflammatory activity of selective FFAR agonists, showing that pharmacological intervention targeting FFAR4, which is a sensor of medium and long chain fatty acids, attenuates intestinal inflammation.