Regulation of Epithelial HIF by Probiotic .

The gastrointestinal tract is home to trillions of microorganisms that interact with their host in profound ways, including regulation of immune, endocrine, and neurological functions. One mechanism by which these microbes interact with their eukaryotic host is through the generation of short-chain fatty acids (SCFAs), which are metabolized by the intestinal epithelium creating a state of "physiologic hypoxia". This hypoxia, in turn, results in stabilization and activation of hypoxia-inducible factor (HIF), a transcription factor family shown to support gut barrier function and homeostasis, in the intestinal epithelium.

Modifying microbially derived short chain fatty acids to promote health.

The intestinal mucosa has evolved to facilitate interactions between the host and the constellation of intestinal microbes, collectively termed the microbiota. A well-orchestrated balance exists in the healthy mucosa where microbes and microbial products first encounter a barrier formed by a single layer of intestinal epithelial cells (IECs). This homeostasis exists at a harsh interface between the highly vascularized mucosa and the anaerobic intestinal lumen.

Mimicry of microbially-derived butyrate reveals templates for potent intestinal epithelial HIF stabilizers.

Microbiota-derived short-chain fatty acids, including butyrate (BA), have multiple beneficial health effects. In the colon, BA concentrations range from 10 to 20 mM and up to 95% is utilized as energy by the mucosa. BA plays a key role in epithelial-barrier regulation and anti-inflammation, and regulates cell growth and differentiation, at least in part, due to its direct influence on stabilization of the transcription factor hypoxia-inducible factor (HIF).