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Nutrition and Health (including climate and ecological aspects)

Causal relationship between gut microbiota and serum vitamin D: evidence from genetic correlation and Mendelian randomization study

Abstract

Background

The gastrointestinal microbiota is emerging as an important mediator in intestinal metabolism, such as vitamin D absorption.

Methods

To elucidate the causality of microbiota and vitamin D, we used linkage disequilibrium score (LDSC) regression and two-sample Mendelian randomization (MR) methods with largest genome-wide association study (GWAS) summary statistics to identify specific taxa that are linked to serum 25-hydroxyvitamin D (25(OH)D).

Results

We found that Ruminiclostridium9 was significantly genetically correlated with 25(OH)D at nominal significance (rg = 0.43, P = 0.04). Applying the inverse variance weighted (IVW) method, we identified that doubling the genetic liability of abundance of Erysipelotrichia, Erysipelotrichaceae and Erysipelotrichales reduced the concentration of 25(OH)D by 0.06 standard deviation (SD) (βIVW = −0.06, s.e. = 0.01, P = 1.48 × 10−6, PFDR = 1.93 × 10−4) and, in turn, one SD increment in genetically determined serum 25(OH)D caused a 0.16 SD decrease in the relative abundance of PhascolarctobacteriumIVW = −0.16, s.e. = 0.04, P = 2.48 × 10−4, PFDR = 0.02) after removing pleiotropic instruments and outliers. Moreover, four MR methods were also used to evaluate causality, the results of which supported these findings. Leave-one-out analyses showed that the results were robust with regard to alterations in the single nucleotide polymorphisms (SNPs) we selected.

Conclusions

In conclusion, our results support the hypothesis that the gut microbiota mediates the absorption of serum vitamin D supplementation and interacts with it closely. These microbiota are potential therapeutic targets for promoting serum vitamin D homeostasis.

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Fig. 1: Diagrammatic description of MR analysis in this study.
Fig. 2: Mendelian randomization study rationale.
Fig. 3: Mendelian randomization estimate using multiple single nucleotide polymorphisms.

Data availability

Data used in this study are publicly available at https://cnsgenomics.com/data/revez_20/ and https://mibiogen.gcc.rug.nl/.

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Acknowledgements

We hereby express our thanks to consortia (UKB, SUNLIGHT, MiBioGen) for kindly releasing GWAS summary data. The study was funded by National Natural Science Foundation of China (81801970 to GTL, 81200596 to YW), Research Foundation from Jiangsu Commission of Health (Z2017018 to YW), and National Natural Science Foundation of Yangzhou (No. YZ2018091 to XNL).

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PJJ, WY, and YXL conceived the research questions and designed the analysis; YXL and ZQT analyzed data; ZL, PYF, LXN and LGT guided and provided feedback on the analysis and interpretation of results; YXL and XXJ wrote the paper. All authors critically reviewed and approved the final manuscript.

Corresponding authors

Correspondence to Jiajia Pan or Ying Wang.

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This study was exempt from ethical approval because all data were anonymous and were based on results from previous publications.

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Yang, X., Zhu, Q., Zhang, L. et al. Causal relationship between gut microbiota and serum vitamin D: evidence from genetic correlation and Mendelian randomization study. Eur J Clin Nutr 76, 1017–1023 (2022). https://doi.org/10.1038/s41430-021-01065-3

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