concept about how a failing kidney and the intestinal microbiota affect each other

concept about how a failing kidney and the intestinal microbiota affect each other

Under physiological conditions, the predominance of symbiotic bacteria, an intact intestinal barrier, defensins production, mucus integrity, and immunoglobulin A (IgA) secretion support the symbiosis between the host and its gut microbiota. An intramural innate immunity controls pathobiont overgrowth inside the lumen of the intestinal tract. (Right part) The metabolic changes that are associated with the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) change the balance of symbionts and pathobionts in a way that favors pathobiont overgrowth, that is dysbiosis. Pathobiont overgrowth induces inflammation and loss of barrier function that in turn promotes increased translocation of bacterial components and even living bacteria into the host’s internal environment. This process will activate innate immunity characterized by production of proinflammatory cytokines that define a state of systemic inflammation. This process potentially modulates a number of clinically relevant processes in CKD such as the progression of CKD, accelerated atherogenesis, and protein wasting.

‘Endotoxin tolerance’ or transient versus persistent activation of innate immunity

Transient activation of, for example, Toll-like receptors (TLRs) stimulates nuclear factor (NF)-κB-dependent secretion of proinflammatory cytokines that triggers systemic inflammation. Repeated or persistent TLR stimulation of monocytes and macrophages induces ‘tolerance’ or ‘compensatory anti-inflammatory syndrome’ that defines a refractory status of the innate immune system. It appears that in chronic kidney disease/end-stage renal disease (CKD/ESRD), both elements of innate immune activation and acquired immunosuppression coexist because some leukocytes are massively activated whereas others remain deactivated. This results in the clinical syndrome of persistent inflammation accompanied by an immunosuppressive state. IL, interleukin; TGF-β, transforming growth factor-β.