Blood Pressure Abnormalities Associated with Gut Microbiota-Derived Short Chain Fatty Acids in Children with Congenital Anomalies of the Kidney and Urinary Tract

Abstract

Both kidney disease and hypertension can originate from early life. Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic kidney disease (CKD) in children. Since gut microbiota and their metabolite short chain fatty acids (SCFAs) have been linked to CKD and hypertension, we examined whether gut microbial composition and SCFAs are correlated with blood pressure (BP) load and renal outcome in CKD children with CAKUT. We enrolled 78 children with CKD stage G1-G4. Up to 65% of children with CAKUT had BP abnormalities on 24 h ambulatory blood pressure monitoring (ABPM). CKD children with CAKUT had lower risk of developing BP abnormalities and CKD progression than those with non-CAKUT. Reduced plasma level of propionate was found in children with CAKUT, which was related to increased abundance of phylum Verrucomicrobia, genus Akkermansia, and species Bifidobacterium bifidum. CKD children with abnormal ABPM profile had higher plasma levels of propionate and butyrate. Our findings highlight that gut microbiota-derived SCFAs like propionate and butyrate are related to BP abnormalities in children with an early stage of CKD. Early assessments of these microbial markers may aid in developing potential targets for early life intervention for lifelong hypertension prevention in childhood CKD.

Keywords: ambulatory blood pressure monitoring; butyrate; cardiovascular disease; children; chronic kidney disease; congenital anomalies of the kidney and urinary tract (CAKUT); gut microbiota; hypertension; propionate; short chain fatty acid.

Figure 1

(A) Variation in fecal bacterial α-diversity analyzed by the Shannon’s diversity indexes. (B) β-diversity changes in gut microbiota across groups by the Partial Least Squares Discriminant Analysis (PLS-DA). (C) Relative abundance of the top 10 phylum of the gut microbiota between the CAKUT and non-CAKUT group. (D) Ratio of Firmicutes to Bacteroidetes (F/B), as a marker of gut dysbiosis. (E) The abundance of phylum Verrucomicrobia in CKD children with CAKUT vs. non-CAKUT. The double asterisk indicates p < 0.01.

Figure 2

(A) Relative abundance of the top 10 genera of the gut microbiota between the CAKUT and non-CAKUT group. (B) Linear discriminant analysis effect size (LEfSe) to identify the taxa that were significantly different between the CAKUT and non-CAKUT group. The threshold of the linear discriminant was set to 3. (C) The abundance of genus Phascolarctobacterium, (D) species Bifidobacterium bifidum, and (E) species Ruminococcus_sp_N15MGS_57 in CKD children with CAKUT vs. non-CAKUT. The asterisk indicates p < 0.05.