Resistant starch alters gut microbiome and metabolomics profiles concurrent with amelioration of chronic kidney disease in rats

Authors: KIEFFER, DOROTHY - University Of California; PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC); VAZIRI, NOSRATOLA - University Of California; LIU, SHUMAN - University Of California; LAU, WEI LING - University Of California; KHAZAELI, MAHYAR - University Of California; NAZERTEHRANI, SOHRAB - University Of California; MOORE, MARY - University Of California; MARCO, MARIA - University Of California; MARTIN, ROY - Louisiana State University

Submitted to: American Journal of Physiology - Renal Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/28/2016
Publication Date: 2/3/2016
Citation: Kieffer, D., Piccolo, B., Vaziri, N., Liu, S., Lau, W., Khazaeli, M., Nazertehrani, S., Moore, M., Marco, M., Martin, R. 2016. Resistant starch alters gut microbiome and metabolomics profiles concurrent with amelioration of chronic kidney disease in rats. American Journal of Physiology - Renal Physiology. 310(9):857-871. doi: 10.1152/ajprenal.00513.2015.

Interpretive Summary: Intestinal bacteria (the "gut microbiome") play an important role in natural, physiological processes that impact our health. The gut microbiome is readily-modified by specific foods and host health, which raises the possibility that prevention of some diseases and reduction in disease risk or progression can be affected by dietary factors that alter bacterial populations. The breadth of specific signals and activities of gut bacteria that are involved in modifying health remain to be determined, prompting the current study that utilized a kidney disease model to determine diet-associated gut microbiome changes that may help explain the protective role of dietary fiber on kidney health. It is known that chronic kidney disease (CKD) causes profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xeno-metabolites). The fermentable dietary fiber—high amylose maize resistant starch type 2 (HAMRS2)—has been shown to alter the gut milieu, and in CKD rat models leads to markedly improved kidney function. We hypothesized that the latter outcome was accompanied by improvements in the gut environment and changes in cecal, blood, and urinary levels of xeno-metabolites, including uremic retention solutes (URS), in rats with CKD. Male Sprague-Dawley rats that specifically develop CKD-like outcomes were fed a low fiber or a high fiber diet (59% w/w of HAMRS2) for 3 weeks. The microbiome was characterized, and hundreds of cecal (gut), serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed altered metabolite profiles, some of which had strong correlations with specific gut bacteria abundances. The outcomes were coincident with improvements in kidney function indices and amelioration of CKD outcomes, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function. These novel results support the concept that increasing intakes of specific dietary fibers will have a protective effect on healthy kidney function and may also help prevent progression toward kidney disease in persons at-risk.

Technical Abstract: Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xeno-metabolites). The fermentable dietary fiber—high amylose maize resistant starch type 2 (HAMRS2)—has been shown to alter the gut milieu, and in CKD rat models leads to markedly improved kidney function. We hypothesized that the latter outcome was accompanied by improvements in the gut environment and changes in cecal, blood, and urinary levels of xeno-metabolites, including uremic retention solutes (URS), in rats with CKD. Male Sprague-Dawley rats were fed chow containing 0.7% adenine for 2 weeks to induce CKD and then switched to a semi-purified, low fiber or a high fiber diet (59% w/w of HAMRS2) for an additional 3 weeks. The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes to Firmicutes ratio. Several URS solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances. The outcomes were coincident with improvements in kidney function indices and amelioration of CKD outcomes, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function.