Deborah Kado, MD, on the Role of Active Vitamin D in the Gut Microbiomes of Older Men

In this podcast, Deborah Kado, MD, discusses her team’s recent study on the association of vitamin D metabolites in the gut microbiomes of older men and what the findings mean our overall health. 

Additional resource:

• Thomas RL, Jiang L, Adams JS, et al. Vitamin D metabolites and the gut microbiome in older mean. Nat Commun. 2020;11(5997). doi:10.1038/s41467-020-19793-8

Deborah Kado, MD is a professor of medicine at the University of California San Diego and the director of the Osteoporosis Clinic for the UCSD Health System. 

TRANSCRIPT: 

Leigh Precopio:  Hello, everyone. Welcome to another installment of Podcasts360, your go‑to resource for medical news and clinical updates. I'm your moderator, Leigh Precopio, with Consultant360 Specialty Network.

While several studies have recently been published suggesting new and important ways that the vitamin D in our gut microbiomes affects our overall health, there continues to be knowledge gaps considering just how vitamin D and our gut microbiomes interact.

In order to further explore this relationship, researchers conducted a study to examine the gut microbiome composition of 567 older men and their vitamin D metabolites.

Joining us today to discuss this study and its implications is Dr. Deborah Kado. Dr. Kado is a professor of medicine at the University of California San Diego School of Medicine and the director of the Osteoporosis Clinic for the UCSD health system. Thank you so much for joining me today, Dr. Kado. Let's dive into your study.

You and your research team examined the relationship between the gut microbiome and vitamin D in older men. What prompted this study?

Deborah Kado:  Opportunity is the first answer in that I'm the principal investigator of the San Diego site of an observational study called the Osteoporotic Fractures in Men Study that originally enrolled about 6,000 men back in 2000. We continue to follow them for risk factors for osteoporosis and fractures to this day.

It turned out that in 2014, at their fourth clinic visit, when these men were about 84 years old, the principal investigator of the study, Dr. Eric Orwoll, from the Oregon Health Sciences University thought to obtain stool specimens from these men who were willing to participate.

Then asked the other investigators, which included me, do I have any questions with regards to how we might use the stool specimens in terms of furthering the science?

The question that I came up with, being the Osteoporosis Clinic director here at UCSD, was "I wonder how the gut microbiome might interact with vitamin D metabolites?" That's how the study came about. Of course, this would be of interest to study in a large, diverse population but it just so happened that I had access to about 600 stool specimens from men who were part of this larger Mr OS Study that involves men who live in six different areas of the United States. Namely, Birmingham, Alabama, near Pittsburgh, Pennsylvania, Minneapolis, Minnesota, Portland, Oregon, Palo Alto, California, as well as San Diego, where I'm from.

Leigh Precopio:  The results of the study indicated that microbiome diversity was associated with active vitamin D and not the precursor form. What is the importance of this finding?

Deborah Kado:  The importance of this finding is that it's acutally very timely. In the past couple of years, we've had results from large randomized controlled trials of vitamin D supplementation. The biggest is probably the VITAL trial of over 25,000 men and women recruited from across the United States, where they were randomized to receive either 2,000 international units of vitamin D3 versus a placebo and followed to see if there would be a difference in the incidence of cancer and cardiovascular outcomes. As you and some of the listeners may know, there's been a lot about vitamin D being very helpful for a variety of conditions. Cancer and cardiovascular disease were among the top. Unfortunately, the trial did not show any benefit for those people who were randomized to the vitamin D supplement versus the placebo. In any of those outcomes, and including even falls and fractures, which is my area of expertise, sometimes some of the people who've looked at the study said, "This is probably because they didn't recruit for people who are vitamin D deficient. Therefore, why would vitamin D help them?" Of those 25,000 people, a good number of them did have vitamin D measures, the precursor form, and they were able to see if they were deficient or not. Looking at those people who were vitamin D deficient and randomized to taking vitamin D versus placebo, there was also no benefit. This called into question what's going on here.

This study that we just published may shed some light onto that in that we were able to show that 125‑dihydroxyvitamin D, the active form, is very much associated with measures of the gut microbiome in older men. Not only that, measures of vitamin D flux, meaning how much is being activated or how much is being metabolized, were also associated with measures of the gut microbial diversity. We did look at the precursor form, and it was a straight line. We saw no association between the precursor form and any measure of the gut microbiome.

Therefore, it suggests that perhaps one of the issues is it's not a one‑size‑fits‑all. We need to better understand what's going on with the metabolism of vitamin D in individuals to better differentiate who may benefit from supplements and who may not.

Leigh Precopio:  The study revealed that 12 particular types of bacteria appeared more frequently in the gut microbiome of the study participants with higher levels of active vitamin D. How might this finding impact how nutritionists and other health care professionals consider the association of vitamin D and the gut microbiome?

Deborah Kado:  In the study, it was interesting that of the 12 particular types of bacteria that were more frequently associated with a healthy gut, these were the butyrate‑producing bacteria that have been described in previous studies as being important for, say, optimal cardiovascular health.

From a nutritionist's standpoint, it would suggest that we know that those butyrate‑producing bacteria produce short‑chain fatty acids. These are derived from foods, usually fruits and vegetables and non‑processed foods. It would suggest that we should be instructing individuals, like our mothers told us, make sure you eat your vegetables off your dinner plate as well as fruits.

Leigh Precopio:  What knowledge gaps still remain concerning the role of vitamin D in the gut microbiome?

Deborah Kado:  In 2021, we still have a lot of knowledge gaps. The first I'd like to highlight is that it is generally accepted that the major site of conversion of the precursor form, 25‑hydroxyvitamin D, to the active form, 125‑dihydroxyvitamin D, occurs in the kidney via the enzyme CYP27B1.

However, results of this study and some mouse studies do implicate the gut and its associated commensal bacteria as important for vitamin D metabolism and that perhaps there is more peripheral conversion of the 25‑hydroxyvitamin D to the 125‑dihydroxyvitamin D, or the active form. While the kidney remains important, we have other options in terms of optimizing a vitamin D metabolism. Clearly more investigation is needed to better understand the cellular mechanisms involved and how the gut bacteria might influence vitamin D metabolism.

The second major knowledge gap is to question whether manipulation or changing either the composition of gut bacteria or vitamin D supplements may improve the health of people in terms of optimizing calcium metabolism and absorption and/or immune function. These would require more interventional studies.

Thirdly, our study results are very exciting. It was an observational study, meaning we only looked at people at one point in time, one draw, their vitamin D levels, and one collection of stools. We can't say this is absolute truth. We need to probably replicate these results in other populations.

Given the robustness of what we found in the types of studies we did, I have pretty good confidence that people will be able to see the same thing in other populations.

Leigh Precopio:  Thank you so much for joining me today and answering all my questions.

Deborah Kado:  Thank you very much, Leigh, for providing me the opportunity to share our exciting study results that I hope will shed light and not heat in terms of understanding the science of vitamin D and how we can use it in the future to optimize the health of our populations.