Study points to link between vitamin D and profile of gut microbiota

In an article published in Metabolism, researchers at the University of São Paulo suggest bloodstream levels of vitamin D can influence gut microbiota composition and cardiometabolic risk.

By Karina Toledo  |  Agência FAPESP – A Brazilian study published in the journal Metabolism suggests that the levels of vitamin D circulating in an organism can influence gut microbiota and hence the risk of cardiovascular and metabolic diseases.

The authors stress that the article presents only indications that the link exists and that it must be confirmed by more extensive research.

“Vitamin D is known to be important for immune system homeostasis. Our study adds the finding that this relationship is due at least in part to interactions with gut microbiota,” said Sandra Roberta Gouvea Ferreira Vivolo, a professor in the University of São Paulo’s Public Health School (FSP-USP) and principal investigator for the research project supported by FAPESP.

The findings are based on an analysis of data from 150 volunteers aged between 20 and 30 (91% of them women) who are taking or have completed an undergraduate course in nutrition. As Vivolo explained, this cross-sectional study is an offshoot of a larger longitudinal study known as the Nutritionist Health Study (NutriHS), which since 2013 has tracked the habits of a specific sample of nutrition students and nutritionists.

“It’s a good idea to evaluate nutritionists, who are used to answering technical questionnaires, especially on food and diet. In addition, their special interest in eating and health is likely to influence their own dietary habits,” Vivolo said.

The first step, she explained, was to find out whether there was a link between consuming more foods rich in vitamin D and having a higher level of the nutrient in the bloodstream.

“This association may seem obvious, but the truth is less straightforward,” Vivolo said. “The findings in the scientific literature are divided: only 20% of our vitamin D comes from diet. The recommended ideal amount can be reached only by exposure to sunlight, which is increasingly rare among city dwellers, or by taking supplements.”

After measuring the level of vitamin D in the participants’ blood and evaluating their eating habits, the group concluded that there was indeed a link between eating more foods rich in vitamin D and higher levels of vitamin D in the bloodstream. The main food sources in the samples were eggs, milk and dairy products in general.

Based on these results, the population surveyed was stratified into three groups: the first with insufficient levels of vitamin D, the second with roughly the recommended level, and the third with higher levels, including participants who used multivitamin supplements.

The next step was to compare the three groups’ health profiles, taking into account such factors as body mass index (BMI), abdominal girth, blood pressure, blood sugar, and insulin sensitivity.

“No significant differences were found in any of these items,” Vivolo said. “We observed merely that participants with high bloodstream levels of vitamin D also had lower levels of lipopolysaccharides.”

Lipopolysaccharides (LPS), she explained, are present in the outer membranes of Gram-negative gut bacteria. Most Gram-negative bacteria are pathogenic, whereas most Gram-positive bacteria are not, and some are even considered beneficial to human health.

“This finding enables us to pose the hypothesis that the individuals with sufficient levels of vitamin D have a healthier gut microbiota composition and that this in turn has a beneficial impact on cardiometabolic risk,” she said.

The LPS molecule is considered immunogenic, i.e., capable of inducing an inflammatory response in the organism. Higher bloodstream levels of LPS, therefore, can favor the development of a state of subclinical (chronic low-grade systemic) inflammation, a factor associated in several studies with the development of cardiovascular and metabolic diseases including diabetes.

“Gut microbiota composition has been associated with the development of diseases, not only infectious diseases but also diseases that involve low-grade inflammation,” Vivolo said. “Vitamin D might play a role in this process, but it’s too soon to point to a cause-and-effect relationship. This requires an intervention study to compare groups that take different amounts of vitamin D for a long period and observe the impact on gut microbiota.

Microbe census

In search of support for their hypothesis, Vivolo and her group conducted a bacterial census in fecal samples from the participants in the study. Using DNA sequencing techniques and statistical methods, the group identified the most frequent phyla and genera among the trillions of microorganisms present in each group of volunteers.

“Only some of the genera identified showed statistically significant differences. For example, Haemophilus and Veillonella, both Gram-negative, were less abundant in participants with more vitamin D. On the other hand, these same volunteers had more bacteria of the genera Coprococcus and Bifidobacterium, both of which are Gram-positive,” Vivolo said.

The results of the analysis were adjusted for possible biases such as the age and gender of the participants, as well as the season of the year, given that differences in exposure to sunshine could influence vitamin D levels. According to Vivolo, after this adjustment, the most significant factor was found to be the association between higher vitamin D levels and greater abundance of Coprococcus and Bifidobacterium, both of which are considered beneficial to human health. Bifidobacteria are classified as probiotic because they favor healthier intestinal flora. Research has shown that they help control the growth of harmful bacteria and mitigate symptoms of allergies and inflammations.

“Our analysis of the results allows us to speculate that the link between vitamin D and gut microbiota is a two-way street,” she said. “We found evidence showing both that the nutrient can influence intestinal flora composition – since vitamin D is a sort of guardian of the organism that favors immune system homeostasis – and vice-versa, that a certain microbiota profile can influence vitamin D levels in the bloodstream. Longitudinal and intervention studies are needed to test these hypotheses.”

The article “Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals” can be retrieved from: sciencedirect.com/science/article/pii/S0026049517300112.