Vitamin D against inflammatory bowel disease: from deficiency to targeted therapy

Inflammatory bowel diseases (IBD) - Crohn's disease and ulcerative colitis - have long ceased to be just a story about immunity. A fresh review in Nutrients draws a line under the accumulated data: vitamin D is not just "about bones", but a moderator of the immune response, microbiota and integrity of the intestinal barrier, and its deficiency in patients with IBD is associated with greater disease activity, worse mucosal healing, infections and osteoporotic risks. The authors call for a transition from the formal "finish up your vitamin" to personalized management of 25(OH)D status - taking into account the IBD phenotype, therapy and comorbidity.

Vitamin D acts via the VDR receptor present in the intestinal epithelium and immune cells. It downregulates proinflammatory Th1/Th17 responses, supports T regulators, reduces TNF-α/IL-6/IL-17/IFN-γ and increases IL-10 and TGF-β. In parallel, it strengthens the barrier function: increases the expression of tight junction proteins (claudin, occludin, ZO), affects the mucin layer and keeps permeability under control. Finally, through its effect on the microbiota, it increases the proportion of butyric acid-producing bacteria (e.g. Faecalibacterium prausnitzii ) and antimicrobial peptides (cathelicidin, β-defensins). Taken together, this explains why low 25(OH)D in IBD patients so often “rhymes” with exacerbations.

Background of the study

Inflammatory bowel diseases (IBD) - Crohn's disease and ulcerative colitis - are growing in prevalence worldwide and increasingly begin at a young age. Their pathogenesis is multicomponent: genetic predisposition, microbiota dysbiosis, epithelial barrier defects and dysregulation of innate/adaptive immunity (with the Th1/Th17 response exceeding T regulators). Against this background, vitamin D can no longer be considered a "bone vitamin": it is a secosteroid hormone with a VDR receptor in the intestinal epithelium and immune cells, affecting the transcription of hundreds of genes, tight mucosal junctions, the production of antimicrobial peptides and the "fine tuning" of inflammation.

In patients with IBD, 25(OH)D deficiency is particularly common: it is affected by malabsorption and steatorrhea during active inflammation, restrictive diets, bowel resections, long-term steroid/PPI therapy, low sun exposure, and reduced physical activity. Low 25(OH)D levels in observational studies are associated with higher disease activity, frequent exacerbations, hospitalizations, infectious complications, and the risk of bone loss. The biological plausibility of such associations is supported by the following mechanisms: vitamin D shifts the cytokine balance towards tolerance (↓TNF-α/IL-6/IL-17/IFN-γ; ↑IL-10), strengthens the barrier (claudin/occludin/ZO-1), modulates the composition of the microbiota (including butyrate producers), and reduces mucosal permeability.

However, intervention data remain heterogeneous. Randomized and prospective studies vary in D doses and forms (D3/D2), baseline 25(OH)D levels, target “sufficiency” thresholds, follow-up duration, and endpoints (clinical indices, faecal calprotectin, endoscopic healing). There are signals that optimization of D status may improve inflammation control and quality of life, and be associated with a better response to biological therapy (anti-TNF, etc.), but causal inferences and therapeutic “prescriptions” still require standardized RCTs. Genetic modifiers (VDR polymorphisms and vitamin D metabolism enzymes) that may explain differences in response between patients are also discussed.

Hence, the current objective of the review: to collect disparate mechanistic and clinical data, to move away from the “one dose fits all” approach to personalized management of 25(OH)D status in patients with IBD, taking into account the disease phenotype, inflammation activity, body mass index, malabsorption risk, concomitant therapy, and seasonality. The practical goal is to integrate vitamin D management into the standard IBD management route along with iron and calcium: regular 25(OH)D monitoring, clear target ranges, correction algorithms, and safety assessment (calcium, kidney function), so that the barrier, microbiota, and immune response do not work “out of sync,” but in favor of remission.

What exactly did the review show?

• Deficiency is common. Patients with IBD often start with low 25(OH)D; this is associated with disease activity, poorer remission, and complications (including infections and bone loss
• The biology fits. D-hormone works simultaneously on three pathogenesis circuits - immunity, barrier, microbiota - which means the intervention is biologically plausible.
• There are already therapeutic hints. Data on adding vitamin D to standard therapy have been systematized: with optimization of 25(OH)D levels, better inflammation control and quality of life are more often seen; interactions with biological drugs (anti-TNF, vedolizumab, ustekinumab) are also discussed.
• "Precision" is needed. The authors propose moving away from "one dose for all" to a precision approach: choosing the form/dose, target level, and frequency of monitoring based on the IBD phenotype, body weight, concomitant therapy, and risk of malabsorption.

Why does this matter to clinicians? Because vitamin D affects more than just the skeleton. In immunosuppressed patients, its deficiency is associated with greater susceptibility to infections; in patients with active inflammation, with impaired mucosal healing. The review also reminds us of the genetic “little things”: polymorphisms in VDR and vitamin D pathway genes can explain differences in response to therapy (including biology). Taken together, this is an argument for systemic management of 25(OH)D status as part of the IBD pathway.

What this means for people with IBD right now

• Check 25(OH)D. Every 3-6 months depending on season, body weight, IBD phenotype, activity and therapy. Low values should be adjusted to the “working” range discussed with a gastroenterologist.
• Discuss the form and dose. In cases of malabsorption and active inflammation, higher doses and strict monitoring are often needed. The required regimen is determined by the doctor - taking into account the risks of hypercalcemia and drug interactions.
• Not just capsules. Sun, diet (fatty fish, fortified foods) and weight are also levers. Optimizing your diet and body weight enhances the effect.

An important methodological part of the review is the mechanistic bridges. In the context of IBD, vitamin D:

• reduces the expression of proinflammatory cytokines and “shifts” the balance of T cells towards tolerance;
• strengthens tight epithelial junctions and reduces barrier “leaky”ness;
• supports commensals and short chain fatty acids, which themselves reduce inflammation;
• may modify response to biological therapy (hints in observational studies and genetic subanalyses).

What should clinics and health systems do?

• Include 25(OH)D screening in the standard IBD route (at the start and dynamically).
• In the protocols, write out target ranges and correction algorithms for different scenarios (remission/exacerbation, BMI>30, malabsorption, steroids/biologics).
• Support research into precision nutrition: selection of “personal” doses, taking into account VDR genetics and microbiota as possible response modifiers.

Of course, the review is not a randomized trial. But it neatly summarizes the mechanisms, observational epidemiology, and clinical signals, as well as the roadmap for the future: large RCTs with “hard” outcomes (remission, hospitalization, surgery), clear 25(OH)D target levels, and stratification by IBD phenotype and concomitant therapy. Until then, the sensible approach is to manage deficiency proactively, as part of a multidisciplinary IBD control strategy.

Conclusion

In IBD, vitamin D is no longer a “vitamin for change,” but a module of immunity, barrier, and microbiota; its status should be monitored and corrected as systematically as we do with iron or calcium.

Source: Dell'Anna G. et al. The Role of Vitamin D in Inflammatory Bowel Diseases: From Deficiency to Targeted Therapeutics and Precise Nutrition Strategies. Nutrients. 2025;17(13):2167. https://doi.org/10.3390/nu17132167