Vitamin D supplementation was linked to less disease activity and inflammation in patients with inflammatory bowel disease (IBD) and promoted a more balanced immune response to the gut microbiome, new research showed.
IBD, which includes Crohn’s disease and ulcerative colitis, is driven in part by the immune system reacting to normally harmless bacteria in the gut, reflecting a breakdown in immune tolerance, according to the authors.
“There is a lot of literature [showing] that an unbalanced gut microbiome (‘dysbiosis’) plays a role in IBD development,” lead author John Mark Gubatan, MD, a gastroenterologist at Mayo Clinic in Jacksonville, Florida, told Medscape Medical News. “We wanted to see if vitamin D could control the way the immune system communicates with gut bacteria in patients with IBD taking vitamin D supplementation and restore a more balanced gut microbiome.
“We were expecting that all antibody binding to gut bacteria (‘immune reactivity’) would be decreased in these patients with IBD after taking vitamin D,” he said. “Instead, we discovered that it depends on the type of antibody. Protective [immunoglobulin A] IgA-binding to gut bacteria was increased, whereas pro-inflammatory IgG-binding to gut bacteria was decreased. Furthermore, we also learned there were more IgA binding to probiotic or beneficial gut bacteria with vitamin D.”
The study suggests that vitamin D may help rebalance how the immune system sees gut bacteria, he said. “That’s an important step toward understanding how we might restore immune tolerance in IBD.”
The study was published online in Cell Reports Medicine.
Promoting Immune Tolerance
Loss of immune tolerance to commensal gut bacteria plays a pivotal role in the pathogenesis of IBD, the authors noted. “Current therapeutic strategies in IBD have focused mainly on targeting dysregulated immune responses, without directly addressing gut microbiome crosstalk with intestinal immunity. Understanding the mechanisms that regulate host immune-microbe interactions and developing ways to restore immune tolerance to gut microbiota could lead to therapeutic strategies to treat or prevent IBD,” they wrote.
The researchers used multi-omics (IgA-SEQ, IgG-SEQ, blood scRNA-seq, and immune repertoire sequencing) to investigate the effects of 12 weeks of vitamin D on host immune-microbe interactions in 48 patients with IBD and low vitamin D.
Participants received weekly vitamin D supplements. Blood and stool samples collected before and after treatment, were analyzed using advanced sequencing to map interactions between immune responses and the gut microbiome.
The researchers found that vitamin D supplementation was associated with increased levels of IgA, which typically is linked to protective immune responses, and decreased levels of IgG, which is often associated with inflammation. The researchers also observed changes in immune signaling pathways and increased activity of regulatory immune cells that help control inflammation.
Taken together, the findings suggested that vitamin D supplementation may help promote a more balanced, protective immune response to the gut microbiome. Further analyses found that vitamin D supplementation also was associated with improvements in disease activity scores and in a stool-based marker of inflammation (fecal calprotectin).
The researchers emphasized that the study was small and not designed to establish cause and effect. “We saw encouraging signals, but this was not a randomized trial,” Gubatan said. “These findings need to be confirmed in larger, controlled studies.
“Current vitamin D supplementation guidelines are meant for bone health and calcium metabolism,” he added. “Our exploratory study highlights there could be potential benefits with vitamin D in controlling the interactions between the immune system and gut microbiome in patients with IBD. Further work is needed to understand the exact vitamin D levels and vitamin D supplementation strategies to support this in patients with IBD and other chronic inflammatory diseases.
“Patients with chronic inflammation may have different vitamin D needs,” he said. “It’s too early to recommend measuring gut microbiome or immune markers to test vitamin D efficacy.”
As a next step, the team will explore whether some of the IgA-bound gut bacteria promoted by vitamin D could be used directly to improve IBD and whether some of the B and T regulatory cells (immune cells that control inflammation), that migrate to the gastrointestinal tract and are increased by vitamin D, are helpful in patients with IBD.
‘Now We Have a Pathway’
American Gastroenterological Association spokesperson Fazia Mir, MD, clinical assistant professor at the University of New Mexico, Albuquerque, and gastroenterologist at Presbyterian Healthcare Services, commented on the study for Medscape Medical News. She said the findings are feasible and reflect “what we have been doing all along. In clinical practice, we goal vitamin D at 50 ng/ml for our IBD patients. Now we have a pathway as to how it is acting to improve inflammation.”
That said, she noted, the type of vitamin D that should be used “needs to be studied in larger studies to ease clinical application,” and additional precision medicine research is needed to help tailor the dose to individual patients.
Meanwhile, she concluded, clinicians should continue replacing vitamin D in their IBD patients to help optimize treatment overall.
Gubatan and this project were supported in part by a Doris Duke Physician Scientist Fellowship Award, CZ Biohub Physician Scientist Scholar Award, NIH NIDDK LRP Award, Stanford Translational Research and Applied Medicine Scholar Award, and Stanford MCHRI Pediatric IBD and Celiac Disease Research Award.
Gubatan received grant funding from Genentech and Gilead Sciences. Mir reported no conflicts of interest.
Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.
