: The intestinal tract is home to a densely populated microbial community whose members have varying sensitivities to oxygen, ranging from aerobes to facultative anaerobes to obligate anaerobes. It is widely thought that the colonic environment is anaerobic. The complexity of bacterial communities along with the dramatic alterations in community structure observed in pathologic states, such as inflammatory bowel disease (IBD), suggests that resident gut microbes may be responsive to alterations in luminal oxygen. Unfortunately, very little data currently exists on the oxygen (O2) content in the colon due to the lack of appropriate methods for quantifying oxygen levels. More critically, evidence elucidating the fundamental mechanism(s) by which the colonic environment is maintained in an anaerobic state is lacking. In Preliminary Data, we show that both colonic tissue and luminal oxygen levels can be measured in vivo non- invasively by the phosphorescence quenching method, making use of non-toxic water- soluble oxygen-sensitive dyes - a technical advance that has led to the following two observations: 1) Partial pressure of oxygen (pO2) in the cecal lumen is remarkably lower than pO2 in the adjacent tissue;2) Inspiration of pure O2 leads to a rapid increase in the cecal tissue pO2 and a more gradual increase in the luminal pO2. Based on these findings, we hypothesize that a dynamic equilibrium is maintained whereby oxygen released by colonic tissue is consumed by the gut microbiota thus maintaining an anaerobic environment. In support of this notion, we also provide data showing that the microbiota adherent to the human colonic mucosa is enriched for aerobic and facultative anaerobes relative to the feces where obligate anaerobes predominate. We further hypothesize that the well-described "dysbiotic" composition of the gut microbiome observed in IBD, with the bloom of aerobic Proteobacteria and Actinobacteria, is a response of the gut microbiota to higher pO2 levels and subsequent oxidative stress.

Public Health Relevance

: Growing evidence suggests that the composition of bacterial populations in the gut, collectively known as the gut microbiota, is associated with a number of important human disease processes. Using a novel approach that permits the measurement of oxygen levels in the intestinal tract, we show that the host and gut microbiota to interact to maintain a dynamic oxygen equilibrium in the gut. Ultimately, the ability to measure intestinal oxygen levels and/or alter the gut microbiota by noninvasively altering host tissue oxygenation may lead to the development of innovative therapeutic approaches in the management of disease states associated with the gut microbiota such as IBD and Clostdrium difficile colitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM103591-01
Application #
8412823
Study Section
Special Emphasis Panel (ZGM1-GDB-2 (MC))
Program Officer
Sledjeski, Darren D
Project Start
2012-12-10
Project End
2016-11-30
Budget Start
2012-12-10
Budget End
2013-11-30
Support Year
1
Fiscal Year
2013
Total Cost
$319,990
Indirect Cost
$119,996
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Wu, Gary D (2014) Diet, the gut microbiome and the metabolome in IBD. Nestle Nutr Inst Workshop Ser 79:73-82
Owyang, Chung; Wu, Gary D (2014) The gut microbiome in health and disease. Gastroenterology 146:1433-6
Holt, Robert W; Zhang, Rongxiao; Esipova, Tatiana V et al. (2014) Cherenkov excited phosphorescence-based pO2 estimation during multi-beam radiation therapy: phantom and simulation studies. Phys Med Biol 59:5317-28
Esipova, Tatiana V; Vinogradov, Sergei A (2014) Synthesis of phosphorescent asymmetrically ?-extended porphyrins for two-photon applications. J Org Chem 79:8812-25
Albenberg, Lindsey; Esipova, Tatiana V; Judge, Colleen P et al. (2014) Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota. Gastroenterology 147:1055-63.e8
Albenberg, Lindsey G; Wu, Gary D (2014) Diet and the intestinal microbiome: associations, functions, and implications for health and disease. Gastroenterology 146:1564-72
Wu, Gary D; Lewis, James D (2013) Analysis of the human gut microbiome and association with disease. Clin Gastroenterol Hepatol 11:774-7