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Assessing the Viability of a Synthetic Bacterial Consortium on the In Vitro Gut Host-microbe Interface
Published on: July 4, 2018
Inflammation-associated nitrate facilitates ectopic colonization of oral bacterium Veillonella parvula in the
Daniel F Rojas-Tapias1,2,3, Eric M Brown1,2, Emily R Temple1
1Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Abstract:
Colonization of the intestine by oral microbes has been linked to multiple diseases such as inflammatory bowel disease and colon cancer, yet mechanisms allowing expansion in this niche remain largely unknown. Veillonella parvula, an asaccharolytic, anaerobic, oral microbe that derives energy from organic acids, increases in abundance in the intestine of patients with inflammatory bowel disease. Here we show that nitrate, a signature metabolite of inflammation, allows V. parvula to transition from fermentation to anaerobic respiration. Nitrate respiration, through the narGHJI operon, boosted Veillonella growth on organic acids and also modulated its metabolic repertoire, allowing it to use amino acids and peptides as carbon sources. This metabolic shift was accompanied by changes in carbon metabolism and ATP production pathways. Nitrate respiration was fundamental for ectopic colonization in a mouse model of colitis, because a V. parvula narG deletion mutant colonized significantly less than a wild-type strain during inflammation. These results suggest that V. parvula harness conditions present during inflammation to colonize in the intestine.
Insights
Inflammation enables oral bacteria Veillonella parvula to thrive in the gut. Nitrate metabolism allows this microbe to utilize new food sources and colonize effectively during gut inflammation.
Area of Science:
- Microbiology
- Gastroenterology
- Metabolic pathways
Background:
- Oral microbes can colonize the intestine, contributing to diseases like inflammatory bowel disease (IBD).
- The mechanisms enabling oral bacteria, such as Veillonella parvula, to expand in the intestinal niche are poorly understood.
- Veillonella parvula, an anaerobic oral bacterium, increases in the gut during IBD.
Purpose of the Study:
- To investigate the metabolic mechanisms enabling Veillonella parvula intestinal colonization during inflammation.
- To determine the role of nitrate metabolism in V. parvula's adaptation to the inflamed intestine.
Main Methods:
- Analysis of V. parvula's metabolic response to nitrate.
- Gene expression analysis of the narGHJI operon.
- Assessment of V. parvula growth on various carbon sources.
- In vivo colonization studies using a mouse model of colitis.
Main Results:
- Nitrate allows V. parvula to switch from fermentation to anaerobic respiration via the narGHJI operon.
- Nitrate respiration enhances V. parvula's growth on organic acids and enables utilization of amino acids and peptides.
- This metabolic shift alters carbon metabolism and ATP production pathways.
- A V. parvula narG deletion mutant showed significantly reduced colonization in a mouse colitis model compared to wild-type.
Conclusions:
- Veillonella parvula utilizes inflammation-associated nitrate to adapt its metabolism for intestinal colonization.
- Nitrate respiration is crucial for V. parvula's ability to colonize the inflamed gut.
- This highlights a mechanism by which oral bacteria exploit inflammatory conditions to expand in the intestine.

