Vitamin D

Cholecalciferol (vitamin D₃), C₂₇H₄₄O

Evidence: Strong

Vitamin D is far more than a bone vitamin. It is a powerful regulator of the immune system, and because a large share of immune activity lives in the gut wall, its relevance to digestive health is increasingly clear. Vitamin D contributes to the normal function of the immune system and has a role in the process of cell division, the renewal process the gut lining depends on, and it also supports the normal absorption and use of calcium.

Vitamin D insufficiency is widespread, particularly in northern climates and through the winter months, which is why we include a reliable daily amount as cholecalciferol (D3), the form the body uses most efficiently. A growing field of research is also mapping a two-way relationship between vitamin D and the gut microbiome.

PubMed indexes over 115,000 peer-reviewed papers on vitamin D.

Selected study 1 of 3

Akimbekov NS, Digel I, Sherelkhan DK, Lutfor AB, Razzaque MS. Vitamin D and the Host-Gut Microbiome: A Brief Overview. Acta Histochemica et Cytochemica. 2020;53(3):33-42. doi:10.1267/ahc.20011

Study summary

Study type: Narrative review.

Observed benefits: Sufficient vitamin D status is associated with more diverse gut microbiota, higher levels of beneficial genera and tighter epithelial junctions across the studies reviewed.

Mechanisms: Acting through the vitamin-D receptor, vitamin D supports antimicrobial peptides and barrier integrity, while microbial metabolites in turn influence receptor activity.

Safety: Standard cautions regarding excessive intake; no new safety data.

Evidence strength: Suggestive, calling for controlled human trials.

Selected study 2 of 3

Aggeletopoulou I, Marangos M, Assimakopoulos SF, Mouzaki A, Thomopoulos K, Triantos C. Vitamin D and Microbiome: Molecular Interaction in Inflammatory Bowel Disease Pathogenesis. The American Journal of Pathology. 2023;193(6):656-668. doi:10.1016/j.ajpath.2023.02.004

Study summary

Study type: Narrative review.

Observed benefits: Optimal vitamin D correlates with higher levels of beneficial taxa, strengthened barrier function and balanced immune signalling.

Mechanisms: Vitamin-D receptor signalling regulates tight-junction proteins, autophagy and antimicrobial peptide release.

Safety: Supplementation generally well tolerated at standard doses.

Evidence strength: Moderate and hypothesis-generating.

Selected study 3 of 3

Ullah H. Gut-vitamin D interplay: Key to mitigating immunosenescence and promoting healthy ageing. Immunity and Ageing. 2025;22:20. doi:10.1186/s12979-025-00514-y

Study summary

Study type: Narrative review.

Observed benefits: Adequate vitamin D alongside a balanced microbiome is associated with lower low-grade inflammation and better-preserved immune resilience with age.

Mechanisms: Vitamin D influences microbial diversity, mucosal integrity and immune signalling, while gut microbes influence vitamin D activation.

Safety: Standard cautions regarding high-dose intake.

Evidence strength: Mechanistic and observational; large intervention trials still needed.