Fig. 3.

Dysbiosis and chronic kidney disease (CKD). CKD impairs the balance between symbionts and pathobionts in a way that favors pathobiont overgrowth. Consequences are as follows: a Impairment of the intestinal barrier by disrupting the colonic epithelial tight junction (ETJ) and decreasing epithelial survival. An increase in loss of integrity in intestinal permeability allows translocation of bacteria and lipopolysaccharide (LPS). b Dysregulation of immune response and inflammation. LPS could activate innate immune cells through toll-like receptor 4 (TLR4)-dependent and nuclear factor kappa B (NF-κB) pathways. Pathobionts stimulate dendritic cells (DCs) that activate a Th17/Th1 T-cell response and enhance production of inflammatory cytokines. c Modification of carbohydrates, protein, and bile acid (BA) fermentation. Proteins are fermented by intestinal pathobionts, which are then converted preferentially into indoxyl-sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine n-oxide (TMAO). The reduction in symbionts, specifically Bifidobacterium, induces a decrease in short-chain fatty acids (SCFAs). Dysbiosis modifies BA levels and composition. INF-γ interferon γ, IL-1 interleukin-1, TNF-α tumor necrosis factor-α. (Adapted with permission from [57])