Vitamin D supplementation may help rebalance immune responses to gut bacteria in people with IBD, though larger controlled studies are needed.
Vitamin D supplements may influence how the immune system reacts to gut bacteria in people with inflammatory bowel disease (IBD), according to a study led by Mayo Clinic and published in Cell Reports Medicine.
The results give scientists a clearer view of the relationship between the gut microbiome and immune activity in this chronic condition. They also suggest possible new directions for treatment.
IBD includes Crohn’s disease and ulcerative colitis, and it affects millions of people around the world. In part, the condition develops when the immune system responds inappropriately to bacteria in the gut that are normally harmless, a sign that immune tolerance has broken down.
Many existing treatments are aimed at calming inflammation. However, scientists still know less about how to rebuild a healthier balance between immune defenses 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.”
Testing immune tolerance in IBD
For the study, researchers followed 48 people with IBD who also had low vitamin D levels. Each participant took weekly vitamin D supplements for 12 weeks. The scientists collected blood and stool samples before and after supplementation, then used advanced sequencing tools to examine how immune responses interacted with the gut microbiome.
Vitamin D shifted immune signals
After vitamin D supplementation, participants showed higher levels of immunoglobulin A (IgA), which is generally tied to protective immune activity, and lower levels of immunoglobulin G (IgG), which is more often connected with inflammation. The researchers also detected shifts in immune signaling pathways and greater activity among regulatory immune cells, which help keep inflammation under control.
Taken together, the results suggest that vitamin D may support a healthier and more protective immune relationship with the gut microbiome.
Early results need confirmation
Vitamin D supplementation was also linked to improvements in disease activity scores and in a stool marker of inflammation. However, the researchers stressed that the study was small and was not designed to prove 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 also advise patients not to change how they use vitamin D without speaking with a medical professional.
“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.”
Reference: “Multi-omics reveal vitamin D regulation of immune-gut microbiome interactions and tolerogenic pathways in inflammatory bowel disease” by John Gubatan, Raoul S. Sojwal, Jiayu Ye, Theresa L. Boye, Jacqueline N. Hoang, Touran Fardeen, Michelle Temby, Samuel J.S. Rubin, Sean P. Spencer, Prasanti Kotagiri, Stephan Rogalla, Michael J. Rosen, Ole Haagen Nielsen, Scott Boyd, Justin Sonnenburg and Sidhartha R. Sinha, 26 March 2026, Cell Reports Medicine.
DOI: 10.1016/j.xcrm.2026.102703
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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