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Our gut microbiomes – the numerous bacteria, viruses and other microbes that live in our digestive tract – play an important role in our health and disease risk in ways that are only just starting to be recognized.
Researchers and collaborators at the University of California at San Diego recently demonstrated in older men that the composition of a person’s gut microbiome is linked to their levels of active vitamin D, a hormone important for bone health and immunity.
The study, published on November 26, 2020 in Nature Communications, also revealed a new understanding of vitamin D and how it is typically measured.
Vitamin D can take several forms, but standard blood tests detect only one, an inactive precursor that can be stored by the body. To use vitamin D, the body must metabolize the precursor into an active form.
“We were surprised to find that the diversity of the microbiome – the variety of types of bacteria in a person’s gut – was closely associated with the active vitamin D, but not the precursor form,” said senior author Deborah Kado, MD. , director of the Osteoporosis Clinic at UC San Diego Health. “Greater gut microbiome diversity is believed to be associated with better overall health.”
Kado led the study for the National Institute on Osteoporotic Fractures in Men (MrOS) funded research group on Osteoporotic Fractures in Men (MrOS), a large multi-site effort that began in 2000. He collaborated with Rob Knight, PhD, professor and director of the Center for Microbiome Innovation at UC San Diego, and co-first authors Robert L. Thomas, MD, PhD, member of 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 Sciences and Human Longevity.
Several studies have suggested that people with low vitamin D levels are at increased risk for cancer, heart disease, worse COVID-19 infections, and other diseases. However, the largest randomized clinical trial to date, with over 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 it may be because these studies only measured the precursor form of vitamin D rather than the active hormone,” said Kado, who is also a professor at UC San Diego School of Medicine and the Herbert Wertheim School of Public Health. “Measures of vitamin D formation and degradation may be better indicators of underlying health problems and who might respond best to vitamin D supplementation.”
The team analyzed stool and blood samples provided by 567 men who participated in MrOS. Participants live in six U.S. cities, their median age was 84, and most reported being in good or excellent health. 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 the vitamin D metabolites (the precursor, the active hormone, and the breakdown product) in each participant’s blood serum.
In addition to discovering a link between active vitamin D and overall microbiome diversity, the researchers also noted that 12 particular types of bacteria appeared more often in the gut microbiomes of men with a lot of active vitamin D. Most of these 12 bacteria produce butyrate, a beneficial fatty acid that helps maintain the health of the intestinal lining.
“Gut microbiomes are really complex and vary a lot from person to person,” Jiang said. “When we find associations, they’re usually not as distinct as we’ve found them here.”
Because they live in different regions of the United States, the men in the study are exposed to different amounts of sunlight, a source of vitamin D. As expected, the men who lived in San Diego, California got more sun and also had the most precursor form of vitamin D.
But the team unexpectedly found no correlation between where the men lived and their level 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 is important how well your body is able to metabolize it into active vitamin D, and perhaps this is what clinical studies need to measure to get a better picture of the vitamin’s role in health.”
“We often find in medicine that more is not necessarily better,” added Thomas. “So, in this case, maybe it’s not the amount of vitamin D you supplement with, but how you encourage your body to use it.”
Kado pointed out that the study was based on a single snapshot over time of the microbes and vitamin D found in the participants’ blood and feces, and those factors can vary over time depending on the environment, diet, sleep habits, drugs and more. According to the team, 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.
Other co-authors of the study include: John S. Adams, UCLA; Zhenjiang Zech Xu, Nanchang University; Jian Shen, Gail Ackermann, UC San Diego; Stefan Janssen, Justus-Liebig-University Gießen; Dirk Vanderschueren, KU Leuven and University Hospitals Leuven; Steven Pauwels, University Hospitals of Leuven, KU Leuven, Hospital of Jessa; and Eric S. Orwoll, Oregon Health & Sciences University.
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