Renal Sensing of Bacterial Metabolites in the Gut-kidney Axis

Abstract

Seminal works have now revealed the microbiota is connected with several diseases, including renal disorders. The balance between optimal and dysregulated host-microbiota interactions has changed completely our understanding of immunity and inflammation. Kidney injury is associated with accumulation of uremic toxins in the intestine, augmented intestinal permeability and systemic inflammation. Intestinal bacteria can signal through innate receptors and induce immune cell activation in lamina propria and release of inflammatory mediators into bloodstream. But gut microbiota can also modulate immune functions through soluble products as short chain fatty acids (SCFAs). The three most common SCFAs are propionate, butyrate and acetate which can signal through specific G-protein coupled receptors (GPCRs) such as GPR43, GPR41 and GPR109a, expressed on the surface of epithelial, myeloid, endothelial and immune cells, among others. The triggered signaling can change cell metabolism, immune cell activation and cell death. Here, we reviewed gut-kidney axis, how kidney cells can sense SCFAs and its implication in renal diseases.

The impact of hypoxia-inducible factors in the pathogenesis of kidney diseases: a link through cell metabolism

“…The partial pressure of oxygen level is low in the gut due to the anatomical juxtaposition of the outermost mucosal surface with the oxygen-depleted lumen and a countercurrent oxygen exchange system in the intestinal villi [ 149 , 150 ]. In addition, the gut contains a diverse and dense microbial population that includes aerobic facultative and anaerobic bacteria necessary for breakdown of food nutrients and regulation of intestinal and systemic immune responses [ 151 , 152 ].…”

“…The roles of the gut microbiota in the healthy gut and in intestinal diseases have been extensively investigated. A regulated host-microbiota interaction is essential for physiologic homeostasis and regulation of the immune system [ 151 , 162 ]. Dysbiosis is the imbalance of the gut microbiota with changes in the host metabolic capacity and inflammatory responses that can result in damage to different organs.…”

Enteroendocrine cells and gut hormones as potential targets in the crossroad of the gut-kidney axis communication

“…Consequently, the heightened levels of lipopolysaccharide (LPS) resulting from compromised intestinal integrity are linked to CKD conditions and progress towards end-stage renal diseases (ESRD) ( Monteiro and Berthelot, 2021 ). One conceivable mechanism involves the recognition of LPS by immune cells residing in the kidneys, thus triggering processes of kidney inflammation ( Huang et al, 2017 ; Foresto-Neto et al, 2021 ). Beyond the leaky gut mechanism, the dysbiosis caused by the consumption of unbalanced diets can also contribute to the development of kidney dysfunction.…”

“…The excessive intake of food can be metabolized by the microbiota, enhancing the production of trimethylamine, which is converted to trimethylamine N-oxide (TMAO) by liver cells. This compound is associated with kidney damage and the progression of CKD ( Stavropoulou et al, 2020 ; Foresto-Neto et al, 2021 ). Together, these findings suggest the existence of interesting mechanisms involving the role of microbiota in the gut-kidney crosstalk.…”

Editorial: Global excellence in renal pharmacology 2022: Central and South America

“…The kidneys are influenced by factors from other organs, and elements originating from the gut, such as microbial metabolites, can impact the outcome of acute kidney injury (AKI) and chronic kidney disease (CKD) ( Foresto-Neto et al, 2021 ). Conversely, kidney diseases can alter the gut microbiota, contributing to kidney damage and establishing a vicious cycle ( Felizardo et al, 2016 ).…”