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The HIF prolyl 4-hydroxylases (HIF-P4H) control hypoxia-inducible factor (HIF), a powerful mechanism regulating cellular adaptation to decreased oxygenation. The gastrointestinal epithelium subsists in “physiological hypoxia” and should therefore have an especially well-designed control over this adaptation. Thus, we assessed the absolute mRNA expression levels of the HIF pathway components, <i>Hif1a</i>, <i>HIF2a</i>, <i>Hif-p4h-1</i>, <i>2</i> and <i>3</i> and factor inhibiting HIF (<i>Fih1</i>) in murine jejunum, caecum and colon epithelium using droplet digital PCR. We found a higher expression of all these genes towards the distal end of the gastrointestinal tract. We detected mRNA for <i>Hif-p4h-1</i>, <i>2</i> and <i>3</i> in all parts of the gastrointestinal tract. <i>Hif-p4h-2</i> had significantly higher expression levels compared to <i>Hif-p4h-1</i> and <i>3</i> in colon and caecum epithelium. To test the roles each HIF-P4H isoform plays in the gut epithelium, we measured the gene expression of classical HIF target genes in <i>Hif-p4h-1^−/−</i>, <i>Hif-p4h-2</i> hypomorph and <i>Hif-p4h-3^−/−</i> mice. Only <i>Hif-p4h-2</i> hypomorphism led to an upregulation of HIF target genes, confirming a predominant role of HIF-P4H-2. However, the abundance of <i>Hif-p4h-1</i> and <i>3</i> expression in the gastrointestinal epithelium implies that these isoforms may have specific functions as well. Thus, the development of selective inhibitors might be useful for diverging therapeutic needs.