Vitamin D changes the intestinal microbiome

This article is part of our special May 2020 issue. Download the full issue here.

Relation

Charoenngam N, Shirvani A, Kalajian TA, Song A, Holick MF. The effect of different doses of oral vitamin D₃Dietary supplementation on gut microbiota in healthy adults: a randomized, double-blind, dose-response study.Anti-cancer res. 2020;40(1):551-556.

Draft

This randomized, double-blind, dose-response study examined the effects of vitamin D₃Nutritional supplementation on the intestinal microbiota.

Participant

Twenty adults with low vitamin D status (defined as serum 25-hydroxyvitamin D [25(OH)D] less than 30 ng/mL).

Study medication and dosage

Participants received either 600, 4,000, or 10,000 IU per day of oral vitamin D₃.

Target parameters

Researchers collected stool samples at baseline and after 8 weeks to identify gut microbiota using 16S rRNA gene amplification and sequencing.

Key insights

Baseline serum 25(OH)D was associated with an increased relative frequency ofAkkermansiaand reduced relative abundance ofPorphyromonas(P<0.05). After the intervention, data analysis showed a dose-dependent increase in the relative frequency ofBacteroidswith a significant difference between the 600 IU group and the 10,000 IU group (P=0.027) andParabacteroideswith a significant difference between the 600 IU group and the 4,000 IU group (P=0.039). Elevated serum 25(OH)D was associated with an increase in beneficial bacteria and a decrease in pathogenic bacteria.

Practice implications

Vitamin D₃Dietary supplementation was associated with a dose-dependent increase in bacteria, which was associated with reduced inflammatory bowel disease activity. This is not the first time that D₃Dietary supplementation has been associated with changes in gut microbiota. A number of studies have monitored the gut microbiota with varying results.

An article by Naderpoor et al. November 2019 reported the results of their randomized clinical trial in which 26 overweight people with vitamin D deficiency received vitamin D and the effects this had on their fecal microbiota.¹This study defined vitamin D deficiency as ≤50 nmol/L (equivalent to 20 ng/mL) in contrast to Charoenngam's 30 ng/mL line. Naderpoor's participants received a loading dose of 100,000 IU, followed by 4,000 IU daily for 16 weeks. Vitamin D supplementation in this previous study increased the abundance of the genus' gut microbiotaLachnospira. After supplementation, participants whose blood vitamin D levels rose to more than 75 nmol/L had higher levels of GenusCoprococcusand lower frequency of the genusRuminococcuscompared to those whose vitamin D levels remained below 50 nmol/L.

Nonetheless, there's something intriguing about the idea that exposing your belly to the sun could alter your gut microbiota.

We also used data from a study by Cantarel et al. from 2015, which examined vitamin D supplementation (5,000 IU per day) for 90 days in women (n=70) with multiple sclerosis (MS) and 8 healthy controls. Fecal microbiome testing showed reduced abundance of the genusRuminococcusand increasedAkkermansiaandFaecalibacteriumin this small group. The MS patients who were not treated with glatiramer showed an increase ofCoprococcus,AkkermansiaandFaecalibacteriumafter vitamin D supplementation.²

Do we know what these various findings mean? There is some consensus that vitamin D supplements alter the gut microbiome. These various studies do not suggest consistency in these changes, although some agreeAkkermansiarises. In recent years,Akkermansia muciniphilahas received positive attention, and many consider greater numbers of them beneficial.Akkermansiaexerts control over basal metabolism and immunity.³Therefore, seeing increased fullness, particularly among the overweight or obese people in Naderpoor's study, would be considered a good thing.

Reading in Charoenngam et al that “Baseline serum 25(OH)D was associated with increased relative abundance ofAkkermansiaand reduced relative abundance ofPorphyromonas(P<0.05)" made my antennae sit up and take notice. It's the bacteriaPorphyromonas Gumsisolated from Alzheimer's disease brains, and this finding is the basis of an intriguing theory that this neurodegenerative condition is triggered by chronic reactions to these bacteria.⁴Although not yet widely accepted as causative, the idea that vitamin D is associated with vitamin D is decreasingPorphyromonasPopulation has a certain appeal.

Somewhere we should mention that several publications suggest that exposure to ultraviolet light alters the gut microbiome and that the effects differ from vitamin D supplementation. Here too, the changes vary between studies.^5.6Nonetheless, there's something intriguing about the idea that exposing your belly to the sun could alter your gut microbiota.

Although we prefer to consider data from human studies, there is a mouse study on vitamin D supplementation that should be mentioned in this discussion.

In a July 2018 paper, Ghaly et al. a study in which they gave high doses of vitamin D to mice treated with dextran sodium sulfate to induce colitis. The mice that received the highest doses of vitamin D (10,000 IU/kg) suffered the most severe colitis.⁷The problem with reading studies done on mice is that we don't know how to extrapolate the results to humans, and this situation is a good example. Still, it wouldn't hurt to keep this study in mind when supplementing with high doses of vitamin D until we're sure some people won't react similarly.

The other thing that wouldn't hurt is the view that part of vitamin D's mechanism of action may be through shifting the gut microbiome rather than systemic biochemical effects on cells in the body. This will not be the first time we have had to enter this paradigm. We have already had to adapt our understanding of metformin's mechanism.⁸