High Dose Vitamin D supplementation alters faecal microbiome and predisposes mice to more severe colitis

Simon Ghaly,Prue H Hart,Angela Baird,Cynthia Forest,Frances Lloyd,Lavinia Gordon,Nadeem O Kaakoush,Borut Klopcic,Danny Mok,Terence Mcgonigle,Shelley Gorman,Roger Bouillon,Ian C Lawrance

doi:10.1038/s41598-018-29759-y

Abstract

Vitamin D has been suggested as a possible adjunctive treatment to ameliorate disease severity in human inflammatory bowel disease. In this study, the effects of diets containing high (D++, 10,000 IU/kg), moderate (D+, 2,280 IU/kg) or no vitamin D (D−) on the severity of dextran sodium sulphate (DSS) colitis in female C57Bl/6 mice were investigated. The group on high dose vitamin D (D++) developed the most severe colitis as measured by blinded endoscopic (p < 0.001) and histologic (p < 0.05) assessment, weight loss (p < 0.001), drop in serum albumin (p = 0.05) and increased expression of colonic TNF-α (p < 0.05). Microbiota analysis of faecal DNA showed that the microbial composition of D++ control mice was more similar to that of DSS mice. Serum 25(OH)D3 levels reduced by 63% in the D++ group and 23% in the D+ group after 6 days of DSS treatment. Thus, high dose vitamin D supplementation is associated with a shift to a more inflammatory faecal microbiome and increased susceptibility to colitis, with a fall in circulating vitamin D occurring as a secondary event in response to the inflammatory process.

Highlights

Vitamin D is recognized as a regulator of both innate and adaptive immune responses[1], and vitamin D deficiency has been associated with the development of a number of immune mediated disorders including the inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC)
D++ mice had significantly higher serum 25(OH)D3 compared to D+ mice which was in turn higher than D− (Table 1)
When examining the overall microbiome composition there is a clear shift for D++ mice towards that of dextran sodium sulphate (DSS) mice (Fig. 7E). This is the first study to examine the effect of high dose vitamin D supplementation in an IBD model

Summary

Introduction

Vitamin D is recognized as a regulator of both innate and adaptive immune responses[1], and vitamin D deficiency has been associated with the development of a number of immune mediated disorders including the inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC). Several confounding factors, such as reduced sunlight exposure, low dietary intake and reduced intestinal absorption, limit the ability to draw conclusions about the causality of the observed link between vitamin D deficiency and active IBD. We sought to investigate the effect of different doses of vitamin D on the faecal microbiota and how this correlated with susceptibility to colitis

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Conclusion