Disruption of intestinal oxygen balance in acute colitis alters the gut microbiome

ABSTRACT

The juxtaposition of well-oxygenated intestinal colonic tissue with an anerobic luminal environment supports a fundamentally important relationship that is altered in the setting of intestinal injury, a process likely to be relevant to diseases such as inflammatory bowel disease. Herein, using two-color phosphorometry to non-invasively quantify both intestinal tissue and luminal oxygenation in real time, we show that intestinal injury induced by DSS colitis reduces intestinal tissue oxygenation in a spatially defined manner and increases the flux of oxygen from the tissue into the gut lumen. By characterizing the composition of the microbiome in both DSS colitis-affected gut and in a bioreactor containing a stable human fecal community exposed to microaerobic conditions, we provide evidence that the increased flux of oxygen into the gut lumen augments glycan degrading bacterial taxa rich in glycoside hydrolases which are known to inhabit gut mucosal surface. Continued disruption of the intestinal mucus barrier through such a mechanism may play a role in the perpetuation of the intestinal inflammatory process.

KEYWORDS:

• Intestine
• colitis
• oxygen
• glycoside hydrolase
• phosphorescence
• microbiota

Disclosure statement

Sergei Vinogradov has partial ownership of Oxygen Enterprises Ltd, which owns patents for the Oxyphor technology.

Author contributions

G.D.W., S.A.V., W.Z., S.R.A, L.L., J.F., and E.S.F designed the study; W.Z., E.S.F, S.R.A., and J.F., performed research; V.T., W.Z., J.F., S.G.D, E.S.F., K.B. and G.D.W. analyzed data; W.Z., E.S.F., S.A.V. and G.D.W. wrote the paper.

Data availability statement

Shallow shotgun sequencing data is available via the Sequence Read Archive (SRA) under submission SUB13752278 and BioProject PRJNA1009084.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2361493

Additional information

Funding

Funding for this project was provided by R01GM103591 (GDW and SAV), [EB028941] (SAV), [T32 AI118684] (WZ), and the Penn Center for Nutritional Science & Medicine [PenNSAM] (ESF, GDW). Histopathology was performed at the Molecular Pathology and Imaging Core (MPIC) and metabolomics was performed at the Host-Microbial Analytic and Repository Core, both at the Center for Molecular Studies in Digestive and Liver Diseases [P30DK050306].