Gut-microbiota metabolites could be associated with renal failure

It’s becoming increasingly recognized that dysbiosis in the gut microbiome can result in the development of sickness or disease.  Understanding these implications, researchers have also turned to studying biomarkers and indicators that can better predict this outcome and disease onset.  A novel and easily detectable biomarker could serve as an indicator of dysbiosis and facilitate therapeutic development.   Renal function decline is a disorder that can eventually lead to chronic kidney disease (CKD )and impacts many people worldwide.  A conglomerate team of researchers investigated whether metabolites produced from bacterial fermentation could serve as early indicators of renal function decline, and whether or not disruption to taxonomic units are detectible in this stage of the disease. 

The researchers measured circulating metabolites in 4439 individual healthy patients with minimal renal function decline.  Estimated glomerular filtration rate (eGFR) was measured as an indicator for reduced renal function, and the onset of CKD was defined by the kidney losing half of its filtration capacity.  It was found that indoxyl-sulfate, p-cresyl-sulfate, and phenylacetylglutamine –metabolic products of gut microbiota fermentation of tyrosine and tryptophan – were associated with reduction in eGFR, suggesting that these markers could be indicators of early renal function decline.  The researchers were also able to correlate these metabolite levels with changes to in intestinal flora.  16S sequencing revealed that 3 operational taxonomic units were correlated with indoxyl-sulfate, 52 with phenylacetylglutamine, and 1 with p-cresyl sulfate. 

Specific changes within the gut microbiome could indicate disease onset, and these changes could perhaps be monitored by circulating metabolic products.  Following metabolic activity could allow clinicians to treat disease early in its progression, and this principle could theoretically apply to a variety of host diseases, not just kidney failure.  Metabolic products of the microbiome could serve as a useful tool that can lead to novel therapy development.  

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