Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-Honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
Pharmaceuticals Research Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd, Mie, Japan.
Clin Exp Nephrol. 2019 Jul;23(7):908-919. doi: 10.1007/s10157-019-01727-4. Epub 2019 Mar 20.
Constipation is frequently observed in patients with chronic kidney disease (CKD). Lactulose is expected to improve the intestinal environment by stimulating bowel movements as a disaccharide laxative and prebiotic. We studied the effect of lactulose on renal function in adenine-induced CKD rats and monitored uremic toxins and gut microbiota.
Wistar/ST male rats (10-week-old) were fed 0.75% adenine-containing diet for 3 weeks to induce CKD. Then, they were divided into three groups and fed as follows: control, normal diet; and 3.0- and 7.5-Lac, 3.0% and 7.5% lactulose-containing diets, respectively, for 4 weeks. Normal diet group was fed normal diet for 7 weeks. The rats were observed for parameters including renal function, uremic toxins, and gut microbiota.
The control group showed significantly higher serum creatinine (sCr) and blood urea nitrogen (BUN) 3 weeks after adenine feeding than at baseline, with a 8.5-fold increase in serum indoxyl sulfate (IS). After switching to 4 weeks of normal diet following adenine feeding, the sCr and BUN in control group remained high with a further increase in serum IS. In addition, tubulointerstitial fibrosis area was increased in control group. On the other hand, 3.0- and 7.5-Lac groups improved sCr and BUN levels, and suppressed tubulointerstitial fibrosis, suggesting preventing of CKD progression by lactulose. Lac groups also lowered level of serum IS and proportions of gut microbiota producing IS precursor.
Lactulose modifies gut microbiota and ameliorates CKD progression by suppressing uremic toxin production.
慢性肾脏病（CKD）患者常出现便秘。乳果糖作为一种二糖泻药和益生元，通过刺激肠道蠕动来改善肠道环境。我们研究了乳果糖对腺嘌呤诱导的 CKD 大鼠肾功能的影响，并监测了尿毒症毒素和肠道微生物群。
Wistar/ST 雄性大鼠（10 周龄）喂食含 0.75%腺嘌呤的饮食 3 周以诱导 CKD。然后，将它们分为三组，分别喂食以下饮食：对照组，正常饮食；3.0-Lac 和 7.5-Lac 组，分别喂食含 3.0%和 7.5%乳果糖的饮食，共 4 周。正常饮食组喂食正常饮食 7 周。观察大鼠的肾功能、尿毒症毒素和肠道微生物群等参数。
对照组在腺嘌呤喂养 3 周后血清肌酐（sCr）和血尿素氮（BUN）显著高于基线，血清吲哚硫酸（IS）增加了 8.5 倍。在腺嘌呤喂养后切换为正常饮食 4 周后，对照组的 sCr 和 BUN 仍然很高，血清 IS 进一步增加。此外，对照组的肾小管间质纤维化面积增加。另一方面，3.0-Lac 和 7.5-Lac 组改善了 sCr 和 BUN 水平，并抑制了肾小管间质纤维化，表明乳果糖可预防 CKD 进展。Lac 组还降低了血清 IS 水平和产生 IS 前体的肠道微生物群的比例。
乳果糖通过抑制尿毒症毒素的产生来改变肠道微生物群并改善 CKD 进展。
