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Vitamin D supplements may impair immunity against gut bacteria in IBD

Vitamin D supplementation may help improve how the immune system responds to gut bacteria in people with inflammatory bowel disease (IBD), according to a Mayo Clinic-led study published in Cell Reports Medicine.

The findings provide new insights into how the immune system and the gut microbiome interact in this chronic condition and point to potential new therapeutic strategies.

IBD, which includes Crohn's disease and ulcerative colitis, affects millions of people around the world.This condition is partly caused by the immune system reacting to normally harmless bacteria in the gut, causing a disruption in the body's so-called tolerance.

While many existing treatments focus on reducing inflammation, less is known about restoring balanced interactions between the immune system and the gut microbiome.

"This study suggests that vitamin D can help restore the way the immune system recognizes intestinal bacteria," said lead author John Mark Gubatan, MD, a gastroenterologist at the Mayo Clinic in Florida."It's an important step in understanding how to restore immune tolerance in IBD."

In the study, researchers evaluated 48 people with IBD who had low vitamin D levels.Participants received weekly vitamin D supplements for 12 weeks.Blood and faecal samples collected before and after treatment were analyzed using forward sequencing to map the interaction between the immune response and the gut microbiome.

Vitamin D supplementation is associated with increased levels of immunoglobulin A (IgA), which is usually associated with a protective immune response, and decreased levels of immunoglobulin G (IgG), which is more often associated with inflammation.The researchers also observed changes in immune signaling pathways and increased activity of immune regulatory cells that help control inflammation.

Together, these findings suggest that vitamin D may help promote a more balanced protective immune response to the gut microbiome.

Vitamin D supplementation was also associated with improved disease outcomes and stool-based inflammation markers.However, the researchers cautioned that the study was small and was not designed to prove cause and effect.

"We saw encouraging signs, but this was not a randomized trial," says Dr. Gubatan."These findings need to be confirmed in larger, controlled studies."

Researchers warn that patients should not change their vitamin D use without medical guidance.

"Vitamin D is widely available, but the dosage must be individualized, especially in patients with chronic inflammation," adds Dr. Gubatan."Patients should work with their health care team."

Multi-omics Reveals Regulation of Immune System Microbial Responses and Vitamin D Tolerogenic Pathways in Inflammatory Bowel Disease, Cell Reports Medicine (2026).DOI: 10.1016/j.xcrm.2026.102703.www.cell.com/cell-reports-2606-20 …

Journal details: Cell Reports Medicine