Abstract
BackgroundConstipation 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.MethodsWistar/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.ResultsThe 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.ConclusionLactulose modifies gut microbiota and ameliorates CKD progression by suppressing uremic toxin production.
Highlights
The estimated prevalence of chronic kidney disease (CKD) is 8–16% worldwide, and Japan has highest prevalence [1]
A recent study in adenine-induced CKD mice reported that lubiprostone, a chloride channel activator used for chronic constipation, stimulates bowel movement and improves the intestinal environment and suppresses the worsening of renal dysfunction by reducing the accumulation of uremic toxins [4]
Ingested adenine is rapidly metabolized to 2,8-dihydroxyadenine, which is relative kidney weights (a) and renal fibrosis (b–d) in adenineinduced chronic kidney disease (CKD) rats
Summary
The estimated prevalence of chronic kidney disease (CKD) is 8–16% worldwide, and Japan has highest prevalence [1]. A recent study in adenine-induced CKD mice reported that lubiprostone, a chloride channel activator used for chronic constipation, stimulates bowel movement and improves the intestinal environment and suppresses the worsening of renal dysfunction by reducing the accumulation of uremic toxins [4]. Lactulose reaches the large intestine in its unchanged form when administered orally. It helps retain intestinal water and electrolytes by increasing the osmotic pressure in the lower intestinal tract. While lactulose is expected to further improve the intestinal environment by its dual function as a disaccharide laxative that stimulates bowel movement and as a prebiotic [6], few reports of its potential effect on the renal function are available. We report our study in adenine-induced CKD rats evaluating the effects of lactulose on the renal function, uremic toxins, and gut microbiota
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