Developing a novel treatment for heart failure

The EU grant provides EUR 2.5 million (just over SEK 28 million) for Fredrik Bäckhed over five years. In the years to come, he and his colleagues will jointly develop the group’s earlier findings further, toward an entirely new treatment strategy designed to influence the gut microbiota.

“Looking for ways to treat the gut microbiota, instead of using drugs to influence the body's cells, is a completely new concept,” says Fredrik Bäckhed, Professor of Molecular Medicine at Sahlgrenska Academy, University of Gothenburg.

Treating the bacteria

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The EU-funded research trajectory is based on findings published by Bäckhed’s group in the journal Cell five years ago, when they showed how type 2 diabetes changes the metabolism of histidine, an amino acid, with the production of imidazole propionate in the bacteria as a result.

In their continued research on this molecule, the group has been able to connect it with fibrosis, which entails the stiffening of various tissues in the body — in this case, especially the heart and liver. The group has conducted several small-scale studies that have supported the notion that the molecule may be linked to heart failure in humans. However, the results need to be repeated in further studies over the next few years.

“Our greatest chance of realizing the concept is probably for it to work in people on the way to developing heart failure. But we hope that the therapy will be effective for those who already have heart failure as well. It would then be a much-needed treatment for heart failure, retaining cardiac pumping capacity, where no evidence-based treatment is currently available,” Bäckhed says.

The treatment will also be highly relevant for the liver disease non-alcoholic steatohepatitis (NASH), for which there is currently no established treatment.

The treatment that the research group is aiming at is therefore an alternative to antibiotics, probiotics, or ordinary drugs affecting the body’s cells. Here, the active substance will target gut bacteria instead, by blocking the enzyme that produces imidazole propionate.

Artificial lab-grown intestine

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In humans, the intestinal microbiome comprises roughly one kilogram of bacteria. By interacting with its host, it affects human health to such a high degree that the microbiome is now increasingly being regarded as an endocrine organ in its own right. In recent years, research has shown that disturbances in the microbiome can contribute to various disorders, including cardiovascular disease, in humans.

“We must also study the overall effect of the new treatment on the gut microbiota, in order to avoid eliminating mechanisms that maintain a favourable environment for bacteria in the gut. So, we’re treating intestinal bacteria in bioreactors, a sort of artificial intestine, in our lab,” Bäckhed says.

He has brought into the project an outstanding research team, with wide-ranging and advanced skills. Experts in microbiology and biochemistry will study how the enzyme works. Meanwhile, physiologists will explore how the molecule affects the progression of fibrosis, and biochemists schooled in structural biology and medicinal chemistry will develop molecules that can be tested for their ability to stop the enzyme’s function. The research group also collaborates with other researchers not only in Sweden but also, for example, in the Netherlands, Germany and the U.S.