Can our microbiome accurately identify diseases … and predict death?
The studies, both published on pre-print server bioRxiv, conclude that our the mix of microbes in our gut can reveal the presence of many diseases better than our own genes can – and can even predict our risk of dying within the next 15 years.
In the first study, led by researchers from Harvard Medical School, researchers reported that the genetic signature of gut microbes – referred to as a Microbiome-Association-Study (MAS) – was 20% better at discriminating between a healthy and an ill person than a person’s own genes – via a Genome-Wide-Association-Study (GWAS).
“We found that metagenomic predictors outperform human common genomic variants in classifying hosts based on phenotype,” wrote the team – led by Braden Tierney at Harvard Medical.
“Our results, while preliminary and focused on a subset of the totality of disease, demonstrate the relative predictive ability of the microbiome, indicating that it may outperform human genetics in discriminating human disease cases and controls,” they added.
Tierney and colleagues evaluated 47 studies investigating links between our microbiome and a total of 13 diseases – including schizophrenia, hypertension, and asthma—all of which are considered ‘complex’ because they are caused by both environmental and genetic factors. They then looked at 24 genome-wide association studies, which correlate specific human genetic variants with diseases, and compared the results.
According to the team, microbiome analysis was 50% better than GWAS at predicting whether someone had colorectal cancer, while the only time GWAS was outperformed MAS was in predicting whether someone had type 1 diabetes.
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“We can use both the microbiome and human genetics in the clinic to improve patient quality of life,” Tierney told Science – adding that the goal of the work is to identify key markers in both sets of genomes that could help diagnose complex diseases.
Enterobacteriacea: the death predictor?
The second study, led by researchers at the University of Turku, investigated a potential link between our microbiome and life span.
In collaboration with several research international research groups, the study analysed data from a Finnish population study known as FINRISK, which has followed the lives and deaths of more than 7,000 people since 1972.
“We investigated links between mortality and the key features of microbiome composition, including alpha and beta diversity, core microbiota, and taxonomic co-occurrence networks,” explained the team, led by Aaro Salosensaari. “We then investigated the overall capacity of taxonomic composition in predicting mortality risk.”
Initially they found significant associations between the abundances of 43 genera and mortality, however at the genera level the team were unable find a specific predictors of mortality.
In order to pinpoint specific taxonomic markers that could predict mortality risk, we complemented the community-level analyses by shifting the focus towards more refined subcommunity analysis. We identified groups of tightly clustered genera based on taxonomic co-occurrence network analysis.
Data from this analysis showed that people with an abundance of Enterobacteriaceae bacteria were 15% more likely to die within the following 15 years.
“We observed the strongest intra-network correlations and mortality associations for the subnetwork that consisted mainly of Enterobacteriaceae genera,” explained the team – adding that this subnetwork was observed in both Western and Eastern Finnish populations.
Salosensaari and colleagues concluded that the analysis provides ‘a systematic quantification’ of the long-term health associations of the human faecal microbiome.
“In spite of using a remarkably heterogeneous outcome variable (all-cause mortality), we could identify specific gut microbiome features that predicted all-cause mortality during the 15-year follow-up,” they said.
The Finnish-led team concluded that the associations they identified suggest that specific configurations of the human gut microbiome may reflect health-associated changes that are linked to increased mortality risk, or may potentially play a unique role in the maintenance of health and development of incident disease
“Until now, prospective long-term data linking microbiome composition with incident outcomes have been unavailable. Our data provide a proof-of-concept that the microbiome can be used to assess the overall mortality risk, and potentially for disease risk assessment,” they said.
“These findings could serve as a solid framework for microbiome profiling in clinical risk prediction, paving the way towards clinical applications of human microbiome sequencing aimed at prediction, prevention, and treatment of disease,” they added, noting that further studies will be needed to evaluate which diseases can be most effectively predicted through microbiome profiling.
Published preprint via bioRxiv, doi: 10.1101/2019.12.31.891978
“The predictive power of the microbiome exceeds that of genome-wide association studies in the discrimination of complex human disease”
Authors: T Tierney, et al
Published preprint via bioRxiv, doi: 10.1101/2019.12.30.19015842
“Taxonomic Signatures of Long-Term Mortality Risk in Human Gut Microbiota”
Authors: Aaro Salosensaari, et al