Investigating causal relationships between the gut microbiota and allergic diseases: A mendelian randomization study

Yiwei Wang; Tian Liu; Zihao Wan; Lin Wang; Jinpao Hou; Mai Shi; Stephen Kwok Wing Tsui

doi:10.3389/fgene.2023.1153847

Investigating causal relationships between the gut microbiota and allergic diseases: A mendelian randomization study

Front Genet. 2023 Apr 12:14:1153847. doi: 10.3389/fgene.2023.1153847. eCollection 2023.

Authors

Yiwei Wang^{1

2}, Tian Liu^{1

3}, Zihao Wan^{4

5}, Lin Wang^{1

6}, Jinpao Hou^{1

7}, Mai Shi^{1

2}, Stephen Kwok Wing Tsui^{1

2

7}

Affiliations

¹ School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
² Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
³ Department of Dermatology, The Third Affiliated Hospital off Sun Yat-Sen University, Guangzhou, Hong Kong SAR, China.
⁴ Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China.
⁵ Department of Orthopaedics and Limb Reconstruction/Paediatric Orthopaedics, South China Hospital of Shenzhen University, Shenzhen, China.
⁶ Advanced Medical Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
⁷ Centre for Microbial Genomics and Proteomics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

Abstract

Observational studies revealed altered gut microbial composition in patients with allergic diseases, which illustrated a strong association between the gut microbiome and the risk of allergies. However, whether such associations reflect causality remains to be well-documented. Two-sample mendelian randomization (2SMR) was performed to estimate the potential causal effect between the gut microbiota and the risk of allergic diseases. 3, 12, and 16 SNPs at the species, genus, and family levels respectively of 15 microbiome features were obtained as the genetic instruments of the exposure dataset from a previous study. GWAS summary data of a total of 17 independent studies related to allergic diseases were collected from the IEU GWAS database for the outcome dataset. Significant causal relationships were obtained between gut microbiome features including Ruminococcaceae, Eggerthella, Bifidobacterium, Faecalibacterium, and Bacteroides and the risk of allergic diseases. Furthermore, our results also pointed out a number of putative associations between the gut microbiome and allergic diseases. Taken together, this study was the first study using the approach of 2SMR to elucidate the association between gut microbiome and allergic diseases.

Keywords: MWAS; allergic disease; genetic varients; genetics; gut microbiota (GM); mendelian randomization.

Grants and funding

This work was made possible by General Research Fund from Research Grants Council of Hong Kong (Reference numbers: 475113, 14175617, 14119219, 14119420) and the Health and Medical Research Fund from Food and Health Bureau of Hong Kong (Reference numbers: 06171016, 07181266).