可发酵膳食纤维通过保护肠道屏障减轻小鼠慢性肾脏病。

Dietary Fermentable Fibers Attenuate Chronic Kidney Disease in Mice by Protecting the Intestinal Barrier.

机构信息

Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Japan.

出版信息

J Nutr. 2018 Apr 1;148(4):552-561. doi: 10.1093/jn/nxy008.

DOI:10.1093/jn/nxy008

PMID:29659957

Abstract

BACKGROUND

Chronic kidney disease (CKD) is a worldwide health problem. Although the pathogenesis of CKD is still unclear, recent studies suggest that systemic inflammation caused by a dysregulated microflora and an impaired intestinal barrier is involved in CKD development.

OBJECTIVE

We investigated the effects of the fermentable dietary fibers (DFs), unmodified guar gum (GG), and partially hydrolyzed GG (PHGG) (i.e., substances with distinct viscosity characteristics) on CKD development, with a particular focus on colonic tight junction (TJ) barriers in mice.

METHODS

Male 7-wk-old ICR mice were fed an AIN-93G diet that contained 0.25% adenine for 2 wk to induce CKD. Mice fed adenine were then divided into 3 groups and fed the unsupplemented diet (CKD) or a diet containing 10% PHGG (CKD+PHGG) or GG (CKD+GG) for 3 wk. Control (CON) mice were fed an AIN-93G diet without adenine throughout the 5-wk experiment. Plasma urea concentration; the colonic TJ proteins zonula occludens (ZO) 1, ZO2, occludin, junctional adhesion molecule A (JAMA), and claudin isoforms; renal inflammatory cytokines tumor necrosis factor α (Tnfa), interleukin (Il ) 1β (Il1b), and Il6; and cecal short-chain fatty acids (SCFAs) and microflora were analyzed.

RESULTS

Compared with the CON, CKD+PHGG, and CKD+GG groups, the CKD group had a 2.2- to 4.4-fold higher plasma urea concentration and greater expression of inflammatory cytokine genes in the kidney, including Tnfa (4.4- to 48-fold), Il1b (4.6- to 56-fold), and Il6 (8.8- to 115-fold). The CON, CKD+PHGG, and CKD+GG groups had greater expression of colonic TJ proteins including ZO1 (2.9- to 3.7-fold), ZO2 (3.4- to 4.3-fold), occludin (3.0- to 3.3-fold), JAMA (4.4- to 5.4-fold), and claudin 7 (2.1- to 2.6-fold) and higher cecal SCFA (1.8- to 3.5-fold) and Lactobacillus (2.7- to 4.0-fold) concentrations than the CKD group.

CONCLUSION

Supplemental feeding with fermentable DFs, such as GG and PHGG, might be effective for the prevention or management of CKD by restoring colonic barrier integrity and microflora composition, as shown in mice.

摘要

背景

慢性肾脏病（CKD）是一个全球性的健康问题。尽管 CKD 的发病机制仍不清楚，但最近的研究表明，失调的微生物群和受损的肠道屏障引起的全身炎症与 CKD 的发展有关。

目的

我们研究了可发酵膳食纤维（DFs），未修饰瓜尔胶（GG）和部分水解瓜尔胶（PHGG）（即具有不同粘度特性的物质）对 CKD 发展的影响，特别是在小鼠的结肠紧密连接（TJ）屏障方面。

方法

雄性 7 周龄 ICR 小鼠喂食含有 0.25%腺嘌呤的 AIN-93G 饮食 2 周以诱导 CKD。喂食腺嘌呤的小鼠随后分为 3 组，分别喂食未补充饮食（CKD）或含有 10% PHGG（CKD+PHGG）或 GG（CKD+GG）的饮食 3 周。对照（CON）小鼠在整个 5 周实验中喂食不含腺嘌呤的 AIN-93G 饮食。分析血浆尿素浓度；结肠 TJ 蛋白闭锁蛋白（ZO）1、ZO2、紧密连接蛋白（occludin）、连接黏附分子 A（JAMA）和 Claudin 同种型；肾脏炎性细胞因子肿瘤坏死因子-α（Tnfa）、白细胞介素（Il）1β（Il1b）和 Il6；以及盲肠短链脂肪酸（SCFA）和微生物群。

结果

与 CON、CKD+PHGG 和 CKD+GG 组相比，CKD 组的血浆尿素浓度高 2.2-4.4 倍，肾脏中炎性细胞因子基因的表达更高，包括 Tnfa（4.4-48 倍）、Il1b（4.6-56 倍）和 Il6（8.8-115 倍）。CON、CKD+PHGG 和 CKD+GG 组的结肠 TJ 蛋白表达更高，包括 ZO1（2.9-3.7 倍）、ZO2（3.4-4.3 倍）、occludin（3.0-3.3 倍）、JAMA（4.4-5.4 倍）和 Claudin 7（2.1-2.6 倍），盲肠 SCFA（1.8-3.5 倍）和乳杆菌（2.7-4.0 倍）浓度更高。