Host-derived nitrate boosts growth of E. coli in the inflamed gut

By Sebastian E. Winter, M. Winter, M. Xavier, Parameth Thiennimitr, Victor Poon, A. M. Keestra, Richard C. Laughlin, G. Gomez, Jing Wu, S. Lawhon and 6 more. Science, 2013

949 citations recorded by the source corpus.

E. coli kNOws How to Win The harmonious existence among the various microbial inhabitants of the gut is critical for good health. However, inflammation from injury or inflammatory bowel disease, can disrupt this balance and lead to the outgrowth of particular bacteria. The outgrowth of members of the Enterobacteriaceae family, which includes Escherichia coli, is often observed. Because E. coli are facultative rather an obligate anaerobes, Winter et al. (p. 708) postulated that they may be able to use by-products of reactive oxygen and nitrogen species, which are produced during inflammation, for anaerobic respiration, thereby edging out other fermenting bacteria. Indeed, in two mouse models of colitis and in a model of intestinal injury, various E. coli strains were able to use host-derived nitrate as an energy source and outcompete mutant strains unable to do this. During inflammation, Escherichia coli uses nitrate respiration to gain a growth advantage over other gut bacteria. 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.

Subfields: Endocrinology, Molecular Biology, Pharmaceutical Science

View Paper: https://www.semanticscholar.org/paper/d663b1af2cdb0a8a500155a2f6a4e129b87aa533

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In Endocrinology

1. G. Núñez
2. N. Inohara
3. Y. Belkaid
4. M. Zeng

In Molecular Biology

1. Curtis Huttenhower
2. Nicola Segata
3. Y. Belkaid
4. G. Núñez
5. M. Zeng
6. Eric G. Pamer
7. N. Inohara
8. Y. Taur

Citations in the corpus

• Antibiotic-Induced Changes in the Intestinal Microbiota and Disease. (2016, background): “coli can utilize nitrate as an electron acceptor for respiration, which confers a selective growth advantage following iNOS (Nos2) gene activation upon DSS-induced inflammation in mice [74].”
• Proteobacteria: A Common Factor in Human Diseases (2017, background): “In fact it has been demonstrated that nitrate produced by the host during inflammatory conditions can be exploited by commensal Enterobacteriaceae which thus become predominant [68].”
• Role of the Microbiota in Immunity and inflammation (2014, background): “Indeed, commensal E. coli, which is benign under homeostatic conditions, is capable of using inflammatory nitric oxides generated by the immune response as an energy source, conferring a significant growth advantage (Winter et al., 2013).”
• Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease (2017, background): “absent in obligate anaerobes belonging to Clostridia and Bacteroidia classes (148, 183, 184).”
• Microbiota-activated PPAR-γ-signaling inhibits dysbiotic Enterobacteriaceae expansion (2017, positive): “coil Nissle 1917 cydA (pSW172) served as recipient for sequential conjugations and sucrose selections using conjugational donor strains carrying plasmids pSW224, pSW225 and pSW237 (4), respectively.”
• Mechanisms and consequences of intestinal dysbiosis (2017, neutral): “coli was confirmed by inhibiting the nitric oxide synthase iNOS with aminoguanidine hydrochloride during colitis in a mouse model [169].”
• Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis (2013, background): “coli in inflammatory bowel disease (Winter et al., 2013).”