Researchers from the University of California (UC), San Diego, and collaborators have recently demonstrated that the makeup of a person’s gut microbiome is linked to their levels of active vitamin D.

Their study, “Vitamin D metabolites and the gut microbiome in older men,” was published recently in the journal Nature Communications. 

“The vitamin D receptor is highly expressed in the gastrointestinal tract where it transacts gene expression. With current limited understanding of the interactions between the gut microbiome and vitamin D, we conduct a cross-sectional analysis of 567 older men quantifying serum vitamin D metabolites using LC-MSMS and defining stool sub-operational taxonomic units from 16S ribosomal RNA gene sequencing data,” the researchers wrote.

The researchers were surprised to find that microbiome diversity was closely associated with active vitamin D, but not the precursor form. Greater gut microbiome diversity is thought to be associated with better health in general.”

Senior author Deborah Kado, director of the Osteoporosis Clinic at UC San Diego Health, led the study for the National Institute on Aging-funded Osteoporotic Fractures in Men (MrOS) Study Research Group, a large, multi-site effort that started in 2000. She collaborated with Rob Knight, PhD, professor and director of the Center for Microbiome Innovation at UC San Diego, Robert L. Thomas, MD, PhD, fellow in the division of endocrinology at UC San Diego School of Medicine, and Serene Lingjing Jiang, graduate student in the biostatistics program at Herbert Wertheim School of Public Health and Human Longevity Sciences.

Recent studies have linked to COVID-19 cases with vitamin D, suggesting adequate levels of vitamin D have reduced complications. However, the largest randomized clinical trial to date, with more than 25,000 adults, concluded that taking vitamin D supplements has no effect on health outcomes, including heart disease, cancer, or even bone health.

“Our study suggests that might be because these studies measured only the precursor form of vitamin D, rather than active hormone,” explained Kado. “Measures of vitamin D formation and breakdown may be better indicators of underlying health issues, and who might best respond to vitamin D supplementation.”

The researchers analyzed stool and blood samples of 567 men participating in MrOS. The researchers used a technique called 16s rRNA sequencing to identify and quantify the types of bacteria in each stool sample based on unique genetic identifiers. They used a method known as LC-MSMS to quantify vitamin D metabolites in each participant’s blood serum.

Not only did the researchers discover a link between active vitamin D and overall microbiome diversity, the researchers observed that 12 particular types of bacteria appeared more often in the gut microbiomes of men with lots of active vitamin D. Most of those 12 bacteria produce butyrate. Butyrate is an essential microbial metabolite with a vital role as a modulator of proper immune function in the host. In the gut, butyrate protects the integrity of the intestinal epithelial barrier. Decreased butyrate levels can lead to a damaged or dysfunctional intestinal epithelial barrier.

“Gut microbiomes are really complex and vary a lot from person to person,” Jiang noted. “When we do find associations, they aren’t usually as distinct as we found here.”

The men who participated in the study live in six cities around the United States. Men who lived in San Diego, California, got the most sun, and they also had the most precursor form of vitamin D. However, the team found no correlations between where men lived and their levels of active vitamin D hormone.

“It seems like it doesn’t matter how much vitamin D you get through sunlight or supplementation, nor how much your body can store,” Kado said. “It matters how well your body is able to metabolize that into active vitamin D, and maybe that’s what clinical trials need to measure in order to get a more accurate picture of the vitamin’s role in health.”

“We often find in medicine that more is not necessarily better,” Thomas added. “So in this case, maybe it’s not how much vitamin D you supplement with, but how you encourage your body to use it.”

Kado noted that the study relied on a single snapshot in time of the microbes and vitamin D found in participants’ blood and stool, so those factors can fluctuate over time depending on a person’s environment, diet, sleep habits, medications, and more. More studies are needed to better understand the role bacteria play in vitamin D metabolism, and to determine whether intervening at the microbiome level could be used to augment current treatments to improve bone and possibly other health outcomes.

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