Host-derived nitrate fuels indole production by Escherichia coli to drive chronic kidney disease progression
Summary
Chronic kidney disease (CKD) is linked to an elevated fecal abundance of Enterobacteriaceae, but the ecological drivers of this shift and its impact on disease progression remain unclear. The uremic toxin indoxyl sulfate is produced from microbiota-derived indole in the liver. Here, we found that in mice with adenine-induced CKD, impaired clearance of indoxyl sulfate elevated mucosal expression of the gene encoding inducible nitric oxide synthase (iNOS). The resulting rise in luminal nitra
Content
# Host-derived nitrate fuels indole production by Escherichia coli to drive chronic kidney disease progression
*Published: 2026 Mar 19*
Chronic kidney disease (CKD) is linked to an elevated fecal abundance of
Enterobacteriaceae, but the ecological drivers of this shift and its impact on
disease progression remain unclear. The uremic toxin indoxyl sulfate is produced
from microbiota-derived indole in the liver. Here, we found that in mice with
adenine-induced CKD, impaired clearance of indoxyl sulfate elevated mucosal
expression of the gene encoding inducible nitric oxide synthase (iNOS). The
resulting rise in luminal nitrate levels promoted Escherichia coli growth by
means of nitrate respiration. Fecal microbiota from CKD patients generated more
indole than feces of healthy controls during anaerobic culture, but only in the
presence of nitrate. Nitrate enhanced indole production by E. coli, thereby
worsening renal pathology in CKD mice, which was mitigated by iNOS inhibition.
DOI: 10.1126/science.ady5217