Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota
Abstract
The unique anatomy and physiology of the intestine in conjunction with its microbial content create the steepest oxygen gradients in the body, which plunge to near anoxia at the luminal midpoint. Far from static, intestinal oxygen gradients ebb and flow with every meal. This in turn governs the redox effectors nitric oxide, hydrogen sulfide, and reactive oxygen species of both host and bacterial origin. This review illustrates how the intestine and microbes utilize oxygen gradients as a backdrop for mechanistically shaping redox relationships and a functional coexistence.
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The ability to switch metabolism from aerobic to largely nitrate-driven anaerobic is a requirement for microbial survival in the GI tract.
“it rapidly becomes clear that the ability to switch metabolism from aerobic to largely nitrate-driven anaerobic is a requirement for microbial survival[267–269].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [267]
In the gut, longitudinally, oxygen concentrations generally fall, with the highest pO2 in the proximal gut including the gastric fundus (77 mmHg; ~10%) and small bowel (30-45 mmHg, ~4-6%), and declining through the colon to concentrations of less than 3 mmHg in the sigmoid colon and rectum.
“Longitudinally, oxygen concentrations generally fall, with the highest pO2 in the proximal gut including the gastric fundus (77mmHg; ~10%) and small bowel (30–45mmHg, ~4–6%), and declining through the colon to concentrations of less than 3 mmHg (ρ%) in the sigmoid colon and rectum[267].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [267]
Diffusion of oxygen from the enteral vasculature through the submucosal tissue and into the intestinal lumen creates a steep oxygen gradient, ranging from 80-100 mmHg (~10-13%) in the submucosa and base of the villi, down to only 8-10 mmHg (~1-2%) in the overlying mucus layer and an essentially anaerobic luminal center.
“Second, diffusion of oxygen from the enteral vasculature through the submucosal tissue and into the intestinal lumen creates an incredibly steep oxygen gradient, ranging from 80–100mmHg (~10–13%) in the submucosa and base of the villi, down to only 8–10mmHg (~1–2%) in the overlying mucus layer and an essentially anaerobic luminal center (Figure 4)[233,267].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [267]
Ecological conditions vary immensely along both the length of the GI tract as well as in cross-section from lumen to the mucosal brush-border.
“Ecological conditions vary immensely along both the length of the GI tract as well as in cross-section from lumen to the mucosal brush-border[173,267,308,309].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [267]
The O2 level at the luminal surface of the intestinal tract has been reported to range from 2% to 7%.
“typically, the O2 level at the luminal surface has been reported to range from 2% to 7% [19–21].”
From Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions (2015) · cites this paper as [19]
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- Authors
- Espey, M. G.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Espey, Michael Graham
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 55
- Pages
- 130-140
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2049085828
- Cited by
- 396
- References
- 159
- Citations by year
- 2026: 26 · 2025: 31 · 2024: 31 · 2023: 31 · 2022: 32 · 2021: 40 · 2020: 32 · 2019: 35 · 2018: 42 · 2017: 32 · 2016: 28 · 2015: 17 · 2014: 10 · 2013: 8
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL92624, R01HL092624)
- National Institute of Neurological Disorders and Stroke (P30NS057098)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- gut microbiota, host-microbe interactions, redox signaling, nitric oxide, hydrogen sulfide, reactive oxygen species
- MeSH terms
- Humans, Intestinal Mucosa, Intestines, Oxidation-Reduction, Oxygen, Microbiota
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