Skip to main content
Fig. 1 | Molecular and Cellular Pediatrics

Fig. 1

From: Bacterial metabolites and cardiovascular risk in children with chronic kidney disease

Fig. 1

Schematic overview of CKD-specific conditions that influence the local biochemical milieu in the colon (A) and contribute to alterations in the composition and metabolism of the gut microbiome (B) leading to disruption of the epithelial barrier function (leaky gut), inflammation, and cardiovascular end-organ damage (C). A In healthy individuals, the biochemical balance in the colon is maintained through a diet rich in fiber providing an energy source for colonocytes and stabilizing local pH as well as downstream metabolism of intestinal microbiota. In contrast, in CKD, several circumstances contribute to a disturbance of biochemical hemostasis. Dietary restrictions (low-fiber diet), oral intake of medications (e.g., antibiotics and phosphate binders), and muscle wasting promote an accumulation of peptides in the gut. Additionally, urea is converted by bacterial-derived urease to ammonium hydroxide which increases the gut pH. Lastly, constipation promotes a prolonged transit time of these metabolites exerting selection pressure on intestinal bacteria. B Under normal circumstances, humans benefit from the symbiotic relationship with their gut microbiota by saccharolytic fermentation of complex carbohydrates resulting in the production of SCFA namely acetate, propionate, and butyrate. Whereas butyrate is mainly used by epithelial cells as a nutrient source, acetate and propionate enter the systemic circulation. Generally, SCFAs promote gut epithelial integrity and balance systemic regulation of adaptive immunity and modulate inflammation response. In CKD, dysbiotic changes are characterized by a shift in the fermentation pattern of bacteria from a health-promoting saccharolytic to a proteolytic fermentation. This alteration not only leads to a decrease in local and systemic SCFA concentration but also promotes fermentation of amino acid tryptophan and tyrosine to uremic acid precursors indoles and cresols respectively. C Intestinal barrier dysfunction (leaky gut), enforced by dysbiosis and local metabolite imbalance, promotes paracellular migration of bacteria and uremic toxins. Renal excretion decline inevitably induces accumulation of these bacterial-derived metabolites. Moreover, lymphocytes infiltrate the colonocytes’ lamina propria and enter systemic circulation resulting in a state of chronic low-grade inflammation. All these factors finally promote endothelial calcification and cardiovascular disease. CKD chronic kidney disease, Tyr tyrosine, Trp tryptophane, Phe phenylalanine, SCFA short-chain fatty acid, VSMC vascular smooth muscle cell

Back to article page