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

Xiaolin Yang; Qingtian Zhu; Lei Zhang; Yufang Pei; Xiaojian Xu; Xinnong Liu; Guotao Lu; Jiajia Pan; Ying Wang

doi:10.1038/s41430-021-01065-3

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

Eur J Clin Nutr. 2022 Jul;76(7):1017-1023. doi: 10.1038/s41430-021-01065-3. Epub 2022 Jan 19.

Authors

Xiaolin Yang^{1

2}, Qingtian Zhu^{1

2}, Lei Zhang³, Yufang Pei⁴, Xiaojian Xu⁵, Xinnong Liu^{1

2}, Guotao Lu^{1

2}, Jiajia Pan⁶, Ying Wang⁷

Affiliations

¹ Institute of digestive diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, PR China.
² Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, PR China.
³ Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu, PR China.
⁴ Department of Epidemiology and Health Statistics, School of Public and Health, Medical College of Soochow University, Suzhou, Jiangsu, PR China.
⁵ Jiangsu Provincial Yangzhou Environmental Monitoring Center, Yangzhou, Jiangsu, PR China.
⁶ Intensive Care Unit, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, PR China. jjpan@yzu.edu.cn.
⁷ Department of Endocrinology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, PR China. wangying1972@yzu.edu.cn.

PMID: 35046567
DOI: 10.1038/s41430-021-01065-3

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 (r_g = 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) (β_IVW = -0.06, s.e. = 0.01, P = 1.48 × 10^-6, P_FDR = 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 Phascolarctobacterium (β_IVW = -0.16, s.e. = 0.04, P = 2.48 × 10^-4, P_FDR = 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gastrointestinal Microbiome* / genetics
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide
Vitamin D
Vitamin D Deficiency* / genetics
Vitamins

Substances

Vitamins
Vitamin D