Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract

European Journal of Nutrition, Jul 2015

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. Results Vitamin D3 supplementation changed the gut microbiome in the upper GI tract (gastric corpus, antrum, and duodenum). We found a decreased relative abundance of Gammaproteobacteria including Pseudomonas spp. and Escherichia/Shigella spp. and increased bacterial richness. No major changes occurred in the terminal ileum, appendiceal orifice, ascending colon, and sigmoid colon or in stools, but the CD8+ T cell fraction was significantly increased in the terminal ileum. Conclusion Vitamin D3 modulates the gut microbiome of the upper GI tract which might explain its positive influence on gastrointestinal diseases, such as inflammatory bowel disease or bacterial infections. The local effects of vitamin D demonstrate pronounced regional differences in the response of the GI microbiome to external factors, which should be considered in future studies investigating the human microbiome.

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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 - 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)


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Mina Bashir, Barbara Prietl, Martin Tauschmann, Selma I. Mautner, Patrizia K. Kump, Gerlies Treiber, Philipp Wurm, Gregor Gorkiewicz, Christoph Högenauer, Thomas R. Pieber. Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract, European Journal of Nutrition, 2016, pp. 1479-1489, Volume 55, Issue 4, DOI: 10.1007/s00394-015-0966-2