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

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 (xenometabolites). 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. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). 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 uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function.

Urea, a true uremic toxin: the empire strikes back

“…Our group recently reported that the prebiotic amylose maize resistant starch, which reaches the colon undigested and is metabolized by bacteria to short-chain fatty acids, improved creatinine clearance and reduced kidney fibrosis in CKD rats [60]. A follow-up study revealed marked improvements in serum, urine and cecal fluid metabolomics in conjunction with decreased gut microbial dysbiosis [61]. A meta-analysis of controlled feeding trials found that fibre supplementation significantly decreased serum urea levels in a pooled cohort of 143 participants but there was significant interstudy heterogeneity and urea lowering was not a doseresponse effect [62].…”

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

“…Our group previously reported that feeding uremic rats amylose maize-resistant starch (a prebiotic) improved creatinine clearance and reduced kidney inflammation and fibrosis [123]. A follow-up study revealed marked improvements in serum, urine, and intestinal fluid metabolomics in conjunction with decreased gut microbial dysbiosis [124]. Resistant starches transit to the colon undigested and are metabolized by bacteria to short-chain fatty acids which are important nutrients to enterocytes.…”

Gut microbiome in chronic kidney disease: challenges and opportunities

“…Results from animal studies show favorable effects of a high fiber diet in restoring intestinal microbiome, and plasma, cecal, and urine metabolome (124). Similarly, rats with CKD fed high resistant starch diet had retardation in progression of CKD.…”