Dysbiotic Proteobacteria expansion: a microbial signature of epithelial dysfunction

- Epithelial hypoxia drives anaerobiosis to maintain dominance of obligate anaerobes.
- Increased epithelial oxygenation disrupts anaerobiosis in the large intestine.
- Elevated oxygen availability drives a shift from obligate to facultative anaerobes.
- Proteobacteria expansion is a microbial signature of colonic epithelial dysfunction.

A balanced gut microbiota is important for health, but the mechanisms maintaining homeostasis are incompletely understood. Anaerobiosis of the healthy colon drives the composition of the gut microbiota towards a dominance of obligate anaerobes, while dysbiosis is often associated with a sustained increase in the abundance of facultative anaerobic Proteobacteria, indicative of a disruption in anaerobiosis. The colonic epithelium is hypoxic, but intestinal inflammation or antibiotic treatment increases epithelial oxygenation in the colon, thereby disrupting anaerobiosis to drive a dysbiotic expansion of facultative anaerobic Proteobacteria through aerobic respiration. These observations suggest a dysbiotic expansion of Proteobacteria is a potential diagnostic microbial signature of epithelial dysfunction, a hypothesis that could spawn novel preventative or therapeutic strategies for a broad spectrum of human diseases.

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