Understanding the link between disease and the microbiome

There is a growing body of evidence indicating that the trillions of microbes that live on and inside our bodies — our ‘microbiome’ — affect our health. Recent research has found that changes in the composition of bacterial communities in the intestines lead to imbalances in metabolic processes the microbiome collectively perform, and that such imbalances are associated with obesity, type 2 diabetes, cancer, autoimmune diseases and certain neurological disorders.

These findings suggest that it might be possible to prevent or treat these conditions with diet, drugs or some other intervention that restores the microbiome’s functional capacity. To do this, though, it is first necessary to determine which bacteria — from the hundreds to thousands of bacterial species that populate different microbiomes in a human body — are responsible for which functional imbalances.

In a paper appearing in the journal Cell Host & Microbe, researchers from the University of Washington School of Medicine report on a new method that reveals how much individual bacterial species contribute to disease-associated functional imbalances in the microbiome.

“This method opens the way to pinpoint which species in our microbiome are responsible for each functional imbalance, so they can be targeted for therapy,” said Elhanan Borenstein, the paper’s senior author and an associate professor of genome sciences.

The ‘Functional Shifts’ Taxonomic Contributors’ method, given the snappy nickname ‘FishTaco’, integrates two common ways scientists look for associations between microbiomes and disease: a taxonomic approach and a functional approach.

The taxonomic approach looks at which species, or taxa, of microbes compose the microbiome, while the functional approach examines all the genes present in a microbiome. Essentially, the taxonomic approach focuses on who is there and the functional approach is on what they are doing.

Each of these approaches, however, tells only part of the story, and it was unclear how to combine the two.

“FishTaco integrates the taxonomic and functional approaches, linking shifts in the microbiome’s species and gene compositions and identifying the taxa that drive functional imbalances observed in different diseases,” Borenstein explained.

In their study, the investigators used FishTaco to analyse the microbiomes of individuals with type 2 diabetes and inflammatory bowel disease, identifying the taxa contributing to functional imbalances in these diseases. They found that functional shifts are often driven by diverse combinations of species. Surprisingly, they further found that very similar functional imbalances observed in different diseases may in fact be driven by a completely different set of species.

“Our findings show that the link between the microbiome taxonomic and functional dynamics is incredibly complex and disease-specific,” Borenstein said. “Identifying the species that drive such imbalances in each disease is therefore an essential step toward targeted interventions aiming to manipulate the functional capacity of the microbiome and promote health.”