Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract
Effects of high doses of vitamin D3 on mucosa‑associated gut microbiome vary between regions of the human gastrointestinal tract
Mina Bashir 0 1 2
Barbara Prietl 0 1 2
Martin Tauschmann 0 1 2
Selma I. Mautner 0 1 2
Patrizia K. Kump 0 1 2
Gerlies Treiber 0 1 2
Philipp Wurm 0 1 2
Gregor Gorkiewicz 0 1 2
Christoph Högenauer 0 1 2
Thomas R. Pieber 0 1 2
0 Institute of Pathology, Medical University of Graz , Graz , Austria
1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz , Graz , Austria
2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz , Auenbruggerplatz 15, 8036 Graz , Austria
3 Thomas R. Pieber
Purpose Vitamin D is well known for its effects on bone mineralisation but has also been attributed immunomodulatory properties. It positively influences human health, but in vivo data describing vitamin D effects on the human gut microbiome are missing. We aimed to investigate the effects of oral vitamin D3 supplementation on the human mucosa-associated and stool microbiome as well as CD8+ T cells in healthy volunteers. Methods This was an interventional, open-label, pilot study. Sixteen healthy volunteers (7 females, 9 males) were endoscopically examined to access a total of 7 sites. We sampled stomach, small bowel, colon, and stools before and after 8 weeks of vitamin D3 supplementation. Bacterial composition was assessed by pyrosequencing the 16S rRNA gene (V1-2), and CD8+ T cell counts were determined by flow cytometry.
Vitamin D; Human gut microbiome; IBD; Inflammation; Gammaproteobacteria
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The human gut is home to about 1014 microorganisms,
which are collectively referred to as the gut microbiome.
These microorganisms work as biochemical factories,
helping the host in nutrient acquisition, vitamin production, and
toxin degradation. Bacterial enzymes are also involved in
an array of metabolic pathways [1] and can even affect the
central nervous system by converting amino acids,
carbohydrates, and other ingested substances into bioactive
compounds [2]. When it comes to energy acquisition, especially
carbohydrate metabolism, the human genome is quite
limited and a healthy gut microbiome is necessary to
effectively digest the diverse carbohydrates [3].
The human gut microbiome is known to have a major
impact on colonisation resistance against intestinal pathogens
[4], on modulation of the intestinal immune system [5], and
on host metabolism [6, 7]. At the current stage of knowledge,
some factors, which influence the composition of the
intestinal microbiome, have been identified, including diet [8–10],
host genetics [11], environmental circumstances [12], and
drugs, such as antibiotics or laxatives [13, 14]. Impairment
of gut homoeostasis has been linked to many gastrointestinal
diseases, such as inflammatory bowel diseases (IBD),
intestinal infections, irritable bowel syndrome (IBS), and colon
cancer [15–18] but also to extra-intestinal diseases, such as
obesity, diabetes mellitus, autoimmune diseases, and neurological
disorders [19]. For general health benefits but also for a
number of diseases, supplementation with vitamin D has shown
to be beneficial. Vitamin D is well known for its role on bone
mineralisation but has also major effects on the immune and
the cardiovascular system as well as on host defence against
pathogenic microorganisms [15, 20–22]. In many parts of the
world, about half of the population is assumed to have
insufficient vitamin D levels (lower than 20 ng/mL serum) due
to a lack of UV exposure and a diet-lacking vitamin D [23].
Sufficient levels of vitamin D have been associated with a
lower risk of autoimmune diseases such as IBD, type 1
diabetes mellitus, and rheumatic diseases, but also neoplasia and
infections such as tuberculosis and hepatitis C [21]. Elevating
serum vitamin D levels to 42 ng/mL has been estimated to
decrease disease rates in various cancers, cardiovascular
diseases, diabetes mellitus, and infections by 10–50 % and the
overall mortality rate by 18 % per year [24].
The hormonal activity of vitamin D has been attributed
to the expression of the vitamin D receptor (VDR), which
has its highest expression in CD8+ T cells compared with
other immune cells [25], and to the vitamin D activating
enzyme CYP27B1. VDR and CYP27B1 are found in
several different cell types including kidneys, muscle, or
prostate, but also in cells of the immune system [25, 26],
supporting a prominent role of vitamin D in gut homoeostasis
and immunity [25]. Given the beneficial effects of vitamin
D, many people are using vitamin D supplementation as
part of their regular diet, but effects of vitamin D on the
human intestinal microbiome have not yet been studied.
We hypothesised that some of the beneficial effects
attributed to vitamin D might be mediated by the gastrointestinal
microbiome. We recruited healthy human volunteers for an
interventional study to assess whether vitamin D3 (...truncated)