Host-Derived Nitrate Boosts Growth of <i>E. coli</i> in the Inflamed Gut

TLDR

Inflammatory gut disorders shift the microbiota by depleting obligate anaerobes and enriching facultative anaerobes such as Enterobacteriaceae, though the host mechanisms driving this shift are unclear. We demonstrate that host‑derived nitrate produced during inflammation fuels anaerobic respiration, giving Escherichia coli a growth advantage in the mouse colon, and that iNOS‑deficient mice lack this benefit, indicating that inflammation selectively promotes Enterobacteriaceae via nitrate.

Abstract

Changes in the microbial community structure are observed in individuals with intestinal inflammatory disorders. These changes are often characterized by a depletion of obligate anaerobic bacteria, whereas the relative abundance of facultative anaerobic Enterobacteriaceae increases. The mechanisms by which the host response shapes the microbial community structure, however, remain unknown. We show that nitrate generated as a by-product of the inflammatory response conferred a growth advantage to the commensal bacterium Escherichia coli in the large intestine of mice. Mice deficient in inducible nitric oxide synthase did not support the growth of E. coli by nitrate respiration, suggesting that the nitrate generated during inflammation was host-derived. Thus, the inflammatory host response selectively enhances the growth of commensal Enterobacteriaceae by generating electron acceptors for anaerobic respiration.