Dietary Fermentable Fibers Attenuate Chronic Kidney Disease in Mice by Protecting the Intestinal Barrier.
Dietary Fermentable Fibers Attenuate Chronic Kidney Disease in Mice by Protecting the Intestinal Barrier.
复制标题
DOI：
10.1093/jn/nxy008
复制
发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
T. Hung;Takuya Suzuki
中科院分区：
文献类型：
--
作者：
T. Hung;Takuya Suzuki
慢性肾脏疾病（CKD）是一个世界性的健康问题。尽管CKD的发病机制尚不清楚，但最近的研究表明，由微生物群失调和肠道屏障受损引起的全身性炎症参与了CKD的发展。目的研究可发酵膳食纤维（DFs）、未改性瓜尔胶（GG）和部分水解瓜尔胶（PHGG）（即具有不同粘度特征的物质）对小鼠结肠紧密连接（TJ）障碍的影响。方法用含0.25%腺嘌呤的AIN-93G日粮诱导7周龄雄性ICR小鼠CKD 2周。然后将腺嘌呤喂养的小鼠分为3组，分别饲喂不添加饲料（CKD）、含10% PHGG （CKD+PHGG）或GG （CKD+GG）的饲料3周。对照组小鼠在5周的实验中饲喂不含腺嘌呤的AIN-93G饲粮。血浆尿素浓度；结肠TJ蛋白occludens zonula (ZO) 1、ZO2、occludin、junctional adhesion molecule A （JAMA）和claudin亚型；肾炎性细胞因子肿瘤坏死因子α (Tnfa)、白细胞介素（Il） 1β (Il1b)、Il6；盲肠短链脂肪酸（SCFAs）和菌群分析。结果与CON、CKD+PHGG和CKD+GG组相比，CKD组血浆尿素浓度高2.2- 4.4倍，肾脏中炎症细胞因子基因表达更高，包括Tnfa（4.4- 48倍）、Il1b（4.6- 56倍）和Il6（8.8- 115倍）。CON、CKD+PHGG和CKD+GG组结肠TJ蛋白的表达更高，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）和乳酸菌（2.7- 4.0倍）浓度高于CKD组。结论在小鼠实验中，添加可发酵的DFs，如GG和PHGG，可能通过恢复结肠屏障完整性和微生物群组成，有效预防或治疗CKD。
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.