Metagenome-wide association studies: fine-mining the microbiome

• Published in: Nature reviews. Microbiology Vol. 14; no. 8; pp. 508 - 522
• Main Authors: Wang, Jun, Jia, Huijue
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-08-2016; Nature Publishing Group
• Subjects: 631/250/249/1313/498; 631/326/2565/2134; 631/443/319/1642/137; 631/61/212/2142; 631/67/1504/1885; 692/699/1503/1702/393; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - microbiology; Arthritis, Rheumatoid - prevention & control; Bacteria - genetics; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - microbiology; Colorectal Neoplasms - prevention & control; Design; Diabetes; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - microbiology; Diabetes Mellitus, Type 2 - prevention & control; Disease; Disease susceptibility; Gastrointestinal Tract - microbiology; Genes; Genetic aspects; Genome-wide association studies; Genome-Wide Association Study; Genomics; Genotype; Health aspects; Health risk assessment; High-Throughput Nucleotide Sequencing; Humans; Identification and classification; Infectious Diseases; Life Sciences; Liver Cirrhosis - diagnosis; Liver Cirrhosis - microbiology; Liver Cirrhosis - prevention & control; Medical Microbiology; Metagenome; Methods; Microbiology; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Obesity - diagnosis; Obesity - microbiology; Obesity - prevention & control; Parasitology; review-article; Rheumatoid arthritis; RNA, Ribosomal, 16S - genetics; ROC Curve; Taxonomy; Virology; China
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro.2016.83

Key Points
Metagenome-wide association studies (MWAS) of human disease are now possible, owing to advances in DNA sequencing and the development of reference gene catalogues and gene clustering methods.
MWAS have identified associations between the microbiome and several major diseases, despite the relatively small sample sizes that have been examined by these studies compared with genome-wide association studies (GWAS).
Common changes to the taxa and functions of the gut microbiota have emerged from MWAS of metabolic diseases.
To advance from the detection of associations to the demonstration that elements of the microbiota contribute to disease will require a range of validations, including mechanistic studies both
in vivo
and
in vitro
. However, even associations that are shown to be non-causal could form the basis of diagnostic markers.
In the future, MWAS may be further developed in numerous ways, including the use of multiomic data, the analysis of genetic variants in metagenomic data and the study of the non-bacterial components of the microbiome.
Metagenome-wide association studies (MWAS) are designed to detect associations between the human microbiome and disease. In this Review, Jia and Wang describe the principal findings of MWAS of human diseases, and consider how these findings might be integrated into medical research and practice.
Metagenome-wide association studies (MWAS) have enabled the high-resolution investigation of associations between the human microbiome and several complex diseases, including type 2 diabetes, obesity, liver cirrhosis, colorectal cancer and rheumatoid arthritis. The associations that can be identified by MWAS are not limited to the identification of taxa that are more or less abundant, as is the case with taxonomic approaches, but additionally include the identification of microbial functions that are enriched or depleted. In this Review, we summarize recent findings from MWAS and discuss how these findings might inform the prevention, diagnosis and treatment of human disease in the future. Furthermore, we highlight the need to better characterize the biology of many of the bacteria that are found in the human microbiota as an essential step in understanding how bacterial strains that have been identified by MWAS are associated with disease.