Compositional and genetic alterations in Graves' disease gut microbiome reveal specific diagnostic biomarkers

Qiyun Zhu; Qiangchuan Hou; Shi Huang; Qianying Ou; Dongxue Huo; Yoshiki Vázquez-Baeza; Chaoping Cen; Victor Cantu; Mehrbod Estaki; Haibo Chang; Pedro Belda-Ferre; Ho-Cheol Kim; Kaining Chen; Rob Knight; Jiachao Zhang

doi:10.1038/s41396-021-01016-7

Compositional and genetic alterations in Graves' disease gut microbiome reveal specific diagnostic biomarkers

ISME J. 2021 Nov;15(11):3399-3411. doi: 10.1038/s41396-021-01016-7. Epub 2021 Jun 2.

Authors

Qiyun Zhu^#^{1

2}, Qiangchuan Hou^#^{3

4

5}, Shi Huang^#^{1

2}, Qianying Ou^#^{3

4}, Dongxue Huo^#^{3

6}, Yoshiki Vázquez-Baeza^{1

2}, Chaoping Cen⁴, Victor Cantu⁷, Mehrbod Estaki¹, Haibo Chang³, Pedro Belda-Ferre^{1

2}, Ho-Cheol Kim⁸, Kaining Chen^{9

10}, Rob Knight^{11

12

13

14}, Jiachao Zhang^{15

16

17}

Affiliations

¹ Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
² Center for Microbiome Innovation, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, USA.
³ School of Food Science and Engineering, Hainan University, Haikou, China.
⁴ Department of Endocrinology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
⁵ Hubei Provincial Engineering and Technology Research Center for Food Ingredients, Hubei University of Arts and Science, Xiangyang, Hubei province, China.
⁶ Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Haikou, China.
⁷ Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
⁸ Scalable Knowledge Intelligence, IBM Research-Almaden, San Jose, CA, USA.
⁹ School of Food Science and Engineering, Hainan University, Haikou, China. [email protected].
¹⁰ Department of Endocrinology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China. [email protected].
¹¹ Department of Pediatrics, University of California San Diego, La Jolla, CA, USA. [email protected].
¹² Center for Microbiome Innovation, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, USA. [email protected].
¹³ Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. [email protected].
¹⁴ Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA. [email protected].
¹⁵ Department of Pediatrics, University of California San Diego, La Jolla, CA, USA. [email protected].
¹⁶ School of Food Science and Engineering, Hainan University, Haikou, China. [email protected].
¹⁷ Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Haikou, China. [email protected].

^# Contributed equally.

Abstract

Graves' Disease is the most common organ-specific autoimmune disease and has been linked in small pilot studies to taxonomic markers within the gut microbiome. Important limitations of this work include small sample sizes and low-resolution taxonomic markers. Accordingly, we studied 162 gut microbiomes of mild and severe Graves' disease (GD) patients and healthy controls. Taxonomic and functional analyses based on metagenome-assembled genomes (MAGs) and MAG-annotated genes, together with predicted metabolic functions and metabolite profiles, revealed a well-defined network of MAGs, genes and clinical indexes separating healthy from GD subjects. A supervised classification model identified a combination of biomarkers including microbial species, MAGs, genes and SNPs, with predictive power superior to models from any single biomarker type (AUC = 0.98). Global, cross-disease multi-cohort analysis of gut microbiomes revealed high specificity of these GD biomarkers, notably discriminating against Parkinson's Disease, and suggesting that non-invasive stool-based diagnostics will be useful for these diseases.

Publication types

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

MeSH terms

Biomarkers
Feces
Gastrointestinal Microbiome* / genetics
Graves Disease*
Humans
Metagenome

Substances

Biomarkers