The gut‐kidney axis in chronic renal failure: A new potential target for therapy

Abstract

Evidence is accumulating to consider the gut microbiome as a central player in the gut-kidney axis. Microbiome products, such as advanced glycation end products, phenols, and indoles, are absorbed into the circulation but are cleared by normal-functioning kidneys. These products then become toxic and contribute to the uremic load and to the progression of chronic kidney failure. In this review, we discuss the gut-kidney interaction under the state of chronic kidney failure as well as the potential mechanisms by which a change in the gut flora (termed gut dysbiosis) in chronic kidney disease (CKD) exacerbates uremia and leads to further progression of CKD and inflammation. Finally, the potential therapeutic interventions to target the gut microbiome in CKD are discussed.

Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease

“…Consistently, fecal transplantation from CKD patients to antibiotic-treated mice results in an increase in the plasma TMAO levels [29]. In contrast, deterioration of kidney function disrupts the intestinal mucosal barrier and contributes to gut dysbiosis [25]. Therefore, CKD may plausibly result in a faulty bidirectional interaction between the gut microbiota and the kidneys.…”

“…Gut-kidney crosstalk, which is largely affected by the gut microbiota, plays an integral role in the development of CKD with reciprocal interactions [25]. The gut microbiota manipulates the processes leading to CKD through inflammatory [25], endocrine [20], and neurologic pathways [90]; a healthy gut microbiota protects the CKD, whereas gut dysbiosis contributes to the development of CKD [2].…”

“…Gut-kidney crosstalk, which is largely affected by the gut microbiota, plays an integral role in the development of CKD with reciprocal interactions [25]. The gut microbiota manipulates the processes leading to CKD through inflammatory [25], endocrine [20], and neurologic pathways [90]; a healthy gut microbiota protects the CKD, whereas gut dysbiosis contributes to the development of CKD [2]. In fact, CKD is associated with alterations in the gut microbiota; species producing uremic toxins, such as Enterobacteriaceae, Clostridiaceae, Pseudomonadaceae, and Bacteroidiaceae, are increased, whereas beneficial species, such as Lactobacillaceae, Bifidobacteriaceae, and Prevotellaceae, are decreased [101][102][103][104].…”

“…Previous studies have demonstrated profound changes in the composition of the gut microbial community in patients and animals with chronic kidney disease (CKD) [24]. The diversity and ratio of bacterial species change in CKD and cardiovascular disease (CVD) patients, implicating possible bidirectional crosstalk between the gut microbiota and the renal and cardiovascular systems [25][26][27]. In fact, spontaneously hypertensive rats (SHRs) were found to have decreased microbial richness with an increased Firmicutes/ Bacteroidetes ratio [28], whereas end-stage renal disease (ESRD) patients were reported to have increased microbial diversity, with an increase in Firmicutes, Actinobacteria, and Proteobacteria and a decrease in Bifidobacteria and Lactobacilli [29].…”

New insights into the gut as the driver of critical illness and organ failure

“…Notably short-chain fatty acids produced by the microbiome improve kidney injury induced by ischemia-reperfusion by modulating the inflammatory process and ameliorating the effects of hypoxia by improving mitochondrial biogenesis (49). Further, microbiome products such as glycation end products, phenols, and indoles can accumulate in the setting of kidney injury and lead to further progression of renal damage (50). …”