Analysis of 1,25-dihydroxyvitamin D genomic action in human enteroids and colonoids reveals multiple regulatory effects of vitamin D in human intestinal physiology.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory study using human organoid cultures (bench research)
PubMed 40535337 · doi:10.3389/fendo.2025.1538463
What was done
The authors evaluated the transcriptomic response to 1,25-dihydroxyvitamin D (1,25(OH)2D3) across human intestinal compartments. Biopsies from the duodenum (Dd) and distal colon (Co) were obtained from 6 subjects per tissue (n = 12 total) to generate human enteroids and colonoids. Organoids were cultured for 3 days in conditions promoting an undifferentiated stem cell phenotype (Un) or differentiated phenotype (Diff). Cultures (DdUn, DdDiff, CoUn, CoDiff) were treated for 24 hours with vehicle control or 100 nM 1,25(OH)2D3, followed by RNA-seq using paired-end Illumina sequencing and differential expression analysis via DESeq2.
What was found
Vitamin D receptor (VDR) mRNA was expressed across all four culture states and was not altered by 1,25(OH)2D3 exposure, intestinal segment, or differentiation status. Classical target genes TRPV6, ATP2B1, and CYP24A1 were induced by 1,25(OH)2D3 across all four culture types, whereas S100G induction occurred exclusively in DdDiff. Across all culture conditions, 63 shared genes were regulated by vitamin D (55 upregulated, 8 downregulated), including pathways for xenobiotic and drug metabolism. Differentiation-specific targets were enriched for lipid metabolism and barrier function regulation via Rho GTPases, whereas genes downregulated in undifferentiated groups were enriched for water transport processes. Segment- and state-specific gene subsets were also identified.
Why it matters
This study maps the direct genomic actions of active vitamin D across distinct anatomical and differentiation axes of healthy human intestinal epithelium, showing that vitamin D influences metabolic, barrier, and transport processes beyond classical calcium absorption.
Limits
The study is restricted to an in vitro organoid culture model and relied on a small sample size (biopsies from 6 donors per intestinal segment). The experiment tested a single 24-hour time point at a single supranormal concentration (100 nM 1,25(OH)2D3). Downstream protein expression and in vivo functional translation were not reported in the abstract.
Cited by
- supports The gastrointestinal tract contains receptors for vitamin D.