Intestinal microbiota dysbiosis in acute kidney injury: novel insights into mechanisms and promising therapeutic strategies

Abstract

In recent years, the clinical impact of intestinal microbiota–kidney interaction has been emerging. Experimental evidence highlighted a bidirectional evolutionary correlation between intestinal microbiota and kidney diseases. Nonetheless, acute kidney injury (AKI) is still a global public health concern associated with high morbidity, mortality, healthcare costs, and limited efficient therapy. Several studies on the intestinal microbiome have improved the knowledge and treatment of AKI. Therefore, the present review outlines the concept of the gut–kidney axis and data about intestinal microbiota dysbiosis in AKI to improve the understanding of the mechanisms of the intestinal microbiome on the modification of kidney function and response to kidney injury. We also introduced the future directions and research areas, emphasizing the intervention approaches and recent research advances of intestinal microbiota dysbiosis during AKI, thereby providing a new perspective for future clinical trials.

Fecal Microbiota Transplantation in Reducing Uremic Toxins Accumulation in Kidney Disease: Current Understanding and Future Perspectives

“…On the other hand, the overgrowth of Anaerosporobacter and Blautia was associated with metabolic dysfunctions in diabetic nephropathy (DN) [ 23 , 24 ]. Interestingly, recent evidence has indicated that intestinal dysbiosis also occurs in acute kidney injury (AKI) [ 25 ]. For instance, Andrianova et al demonstrated by an in vivo study that alterations in the microbiome composition occurred following renal ischemia/reperfusion injury (IRI), and several bacteria including Rothia and Staphylococcus were linked to the high degree of injury [ 26 ].…”

“…Compared with CKD, interest in uremic toxins in AKI was in its infancy in 2009, and the existence of gut–kidney crosstalk in AKI was frequently debated. Today, it is well-established through a variety of experimental animal studies and clinical trials that acute renal damage negatively shapes the microbiota composition [ 25 ]. Importantly, the AKI–microbiota relationship is bidirectional: on the one hand, AKI can cause dysbiosis; on the other hand, the microbial shift influences the severity of the renal injury.…”

The Molecular Mechanism and Therapeutic Strategy of Cardiorenal Syndrome Type 3

“…There is now evidence that intestinal dysbiosis is closely linked to AKI, shedding light on kidney-intestine crosstalk in AKI [176][177][178]. Zhu et al [179] demonstrated that the supplementation of Lactobacillus casei Zhang could prevent AKI and impede the progression of CKD by improving intestinal flora, increasing the levels of short chain fatty acids (SCFAs) and nicotinamide in the serum and kid-Yang et al [176] reported that the increase of Enterobacteriaceae and the decrease of Lactobacillus and Ruminococcus were hallmarks of dysbiosis induced by IRI and were related to the decreased levels of SCFAs, intestinal inflammation, and the leaky gut.…”

The Role of Gut-Derived, Protein-Bound Uremic Toxins in the Cardiovascular Complications of Acute Kidney Injury

“…The gut–kidney axis has been investigated in a number of clinical studies, mostly in CKD [ 108 , 109 , 110 , 111 ]. In septic AKI, impaired gut barrier permeability, with the translocation of bacterial and inflammatory molecules, has also been shown to be associated with the progression of kidney injury and the AKI to CKD transition [ 112 , 113 ]. However, more clinical data are needed to precisely explore the gut–kidney axis and both PUBT generation and accumulation in AKI.…”