JACKSONVILLE, Fla. — Vitamin D supplementation may help shape 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 offer new insight into how the immune system and 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 worldwide. The condition is driven in part by the immune system reacting to normally harmless bacteria in the gut, reflecting a breakdown in what is known as immune tolerance.
While many current therapies focus on reducing inflammation, less is understood about how to restore balanced interactions between the immune system and the gut microbiome .
"This study suggests vitamin D may help rebalance how the immune system sees gut bacteria," says lead author John Mark Gubatan, M.D. , a gastroenterologist at Mayo Clinic in Florida. "That's an important step toward understanding how we might 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 stool samples collected before and after treatment were analyzed using advanced sequencing to map interactions between immune responses and the gut microbiome.
Vitamin D supplementation was associated with increased levels of immunoglobulin A (IgA), which is typically linked to protective immune responses, and decreased levels of immunoglobulin G (IgG), more often associated with inflammation. The researchers also observed changes in immune signaling pathways and increased activity of regulatory immune cells that help control inflammation.
Together, these findings suggest vitamin D may help promote a more balanced, protective immune response to the gut microbiome.
Vitamin D supplementation was also associated with improvements in disease activity scores and a stool-based marker of inflammation. However, the researchers emphasize the study was small and not designed to establish cause and effect.
"We saw encouraging signals, but this was not a randomized trial," Dr. Gubatan says. "These findings need to be confirmed in larger, controlled studies."
The researchers caution that patients should not change their vitamin D use without medical guidance.
“Vitamin D is widely available, but dosing needs to be individualized, especially in patients with chronic inflammation,” Dr. Gubatan adds. “Patients should work with their healthcare team.”
This work was supported by a grant from Doris Duke Physician Scientist Fellowship Award (Grant #2021091), Chan Zukcerberg Biohub Physician Scientist Scholar Award, and National Institutes of Health (NIH) NIDDK LRP Award (2L30 DK126220).
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Cell Reports Medicine
Multi-omics Reveal Vitamin D Regulation of Immune-Gut Microbiome Interactions and Tolerogenic Pathways in Inflammatory Bowel Disease
26-Mar-2026