The causality between gut microbiome and anorexia nervosa: a Mendelian randomization analysis

Xuan Xia; Shu-Yang He; Xiao-Lin Zhang; Decheng Wang; Qian He; Qing-Ao Xiao; Yong Yang

doi:10.3389/fmicb.2023.1290246

The causality between gut microbiome and anorexia nervosa: a Mendelian randomization analysis

Front Microbiol. 2023 Oct 19:14:1290246. doi: 10.3389/fmicb.2023.1290246. eCollection 2023.

Authors

Xuan Xia^{1

2

3}, Shu-Yang He⁴, Xiao-Lin Zhang^{5

6}, Decheng Wang^{1

2

3}, Qian He⁷, Qing-Ao Xiao¹, Yong Yang⁴

Affiliations

¹ Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang, China.
² Institute of Infection and Inflammation, China Three Gorges University, Yichang, China.
³ Department of Physiology and Pathophysiology, College of Basic Medical Science, China Three Gorges University, Yichang, China.
⁴ Department of Critical Care Medicine, Yiling People's Hospital of Yichang City, Yichang, China.
⁵ Department of Interventional Radiology, The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
⁶ Yichang Central People's Hospital, Yichang, China.
⁷ Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, China.

Abstract

Background and aim: Nutrient production by intestinal microbiota corresponds to regulate appetite while gut microbial composition was influenced by diet ingestion. However, the causal relationship between gut microbial taxa and anorexia nervosa (AN) remains unclear. Mendelian Randomization (MR) is a novel research method that effectively eliminates the interference of confounding factors and allows for the exploration of the direct causal effects between exposure and outcome. This study employs MR to explore the causal effect between AN and specific gut microbiome.

Methods: Large-scale Genome Wide Association Study (GWAS) data of AN and 211 gut microbes were obtained from the IEU open GWAS project and Mibiogen Consortium. Two-sample MR was performed to determine the causal relationship between gut microbiota and AN. Furthermore, a bi-directional MR analysis was to examine the direction of the causal relations. The Bonferroni correction test was used to adjust potential correlations among microbial taxa.

Result: In forward MR analysis, 10specific gut microbial taxa have an impact on the occurrence of AN (the p value of IVW <0.05). The high abundance of Genus Eubacteriumnodatumgroup ID: 11297 (OR:0.78, 95% CI:0.62-0.98, p = 0.035) and Class Melainabacteria ID: 1589 (OR:0.72, 95% CI:0.51-0.99, p = 0.045) may be considered protective factors for AN. But after Bonferroni correction, only Class Actinobacteria ID:419 (OR:1.53, 95% CI:1.19-1.96, p = 0.00089) remained significantly associated and high abundance of Class Actinobacteria ID:419 considered as a risk factor for AN. In the reverse MR analysis, AN influences 8 gut microbial taxa with none-statistically significant associations after adjustment.

Conclusion: We identified a significant correlation between AN and 18 microbial taxa which have not been previously reported. Among them, 10 kinds of gut bacteria may affect the occurrence of AN, and the status of AN would affect 8 kinds of gut bacteria. After correction, the Class Actinobacteria ID:419 continued to exert an influence on AN.

Keywords: Mendelian randomization; anorexia nervosa; causality; genome-wide association study; gut microbiome.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Open Foundation of Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University (2023KZL012), National Natural Science Foundation of China (No. 31772709, 82100473), and Hubei Natural Science Foundation (2015CFB316) of China.