SUN-159 RENAL PROTECTIVE EFFECT OF LACTULOSE TARGETING OF GUT-KIDNEY AXIS

Abstract

With the dramatic development of microbiome research in the last decades, gut-kidney axis which is interaction between intestinal environment and kidney has drawn attention, and it was reported that lubiprostone, a novel laxative, improved the intestinal environment and suppressed deterioration of renal function in renal failure (RF) mice. Chronic kidney disease (CKD) patients frequently suffer from constipation, and their compositions of gut microbiota differ from healthy people; implying that gut-kidney axis is disrupted in CKD patients. The target for improving gut-kidney axis in CKD is relief from constipation, improvement in the intestinal environment, and suppression of uremic toxins accumulation. Lactulose, synthetic disaccharide, alters the intestinal environment by stimulating bowel movements as a disaccharide laxative and prebiotic, therefore, it is expected to affect gut-kidney axis. However, because there are few reports evaluating its effect on renal function, the effectiveness of lactulose on CKD is unclear. Thus, we evaluated the effect of lactulose on renal function in adenine-induced RF rats. Wistar/ST male rats (10-week-old) were fed 0.75% adenine-containing diet for 3 weeks to induce RF. Then, they were fed 3.0% or 7.5% lactulose-containing diets for 4 weeks. The rats were observed for parameters including renal function, uremic toxins and gut microbiota. RF rats exhibited increased serum creatinine and blood urea nitrogen (BUN), renal fibrosis accompanying accumulation of serum uremic toxins, and alteration of the intestinal environment. Lactulose reduced serum uremic toxins such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and improved renal fibrosis. Additionally, analysis of the gut microbiota showed the slightly increase in Bifidobacterium, saccharolytic bacteria, and the decrease in Bacteroides which contributed to production of indole is metabolized to IS in the liver. These results suggest that lactulose modifies gut microbiota and ameliorates CKD progression by suppressing uremic toxins accumulation. Our study first discovered the renal protective effect of lactulose via relief from uremia and showed the possibility of lactulose as a gut-kidney axis regulator.