Vitamin A- and D-Deficient Diets Disrupt Intestinal Antimicrobial Peptide Defense Involving Wnt and STAT5 Signaling Pathways in Mice

• Published in: Nutrients Vol. 15; no. 2; p. 376
• Main Authors: Filipe Rosa, Louisa, Petersen, Patricia P, Görtz, Lisa F, Stolzer, Iris, Kaden-Volynets, Valentina, Günther, Claudia, Bischoff, Stephan C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.01.2023; MDPI
• Subjects: Animals; Antiinfectives and antibacterials; Antimicrobial agents; Antimicrobial Peptides; Cadmium; Cell culture; Colon; Defensins; Diet; Disease; Gene expression; gut barrier; Ileum; Inflammation; Inflammatory bowel disease; Intestine; Irritable bowel syndrome; Jak/STAT; Kinases; Laboratory animals; Lysozyme; Matrilysin; Matrix metalloproteinase; Matrix metalloproteinases; Metalloproteinase; Mice; Mice, Inbred C57BL; Microscopy; Muramidase; Nutrient deficiency; Organoids; Peptides; Permeability; Plasmids; Retinene; RNA, Messenger - genetics; Signal Transduction; Small intestine; Stat5 protein; STAT5 Transcription Factor; Villus; Vitamin A; Vitamin D; Vitamins; Wnt protein; Wnt signaling pathway; United States > US; Germany; Wnt signaling pathway; vitamin A; vitamin D; Jak/STAT; MAPk; gut barrier; antimicrobial peptides
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15020376

Vitamin A and D deficiencies are associated with immune modulatory effects and intestinal barrier impairment. However, the underlying mechanisms remain unclear. C57BL/6J mice were fed either a diet lacking in vitamin A (VAd), vitamin D (VDd) or a control diet (CD) for 12 weeks. Gut barrier function, antimicrobial peptide (AMP) defense and regulatory pathways were assessed. VAd mice compared to CD mice showed a reduced villus length in the ileum (p < 0.01) and decreased crypt depth in the colon (p < 0.05). In both VAd- and VDd-fed mice, ileal α-defensin 5 (p < 0.05/p < 0.0001 for VAd/VDd) and lysozyme protein levels (p < 0.001/p < 0.0001) were decreased. Moreover, mRNA expression of lysozyme (p < 0.05/p < 0.05) and total cryptdins (p < 0.001/p < 0.01) were reduced compared to controls. Furthermore, matrix metalloproteinase-7 (Mmp7) mRNA (p < 0.0001/p < 0.001) as well as components of the Wnt signaling pathway were decreased. VAd- and VDd-fed mice, compared to control mice, exhibited increased expression of pro-inflammatory markers and β-defensins in the colon. Organoid cell culture confirmed that vitamins A and D regulate AMP expression, likely through the Jak/STAT5 signaling pathway. In conclusion, our data show that vitamin A and D regulate intestinal antimicrobial peptide defense through Wnt and STAT5 signaling pathways.