Fredrik Bäckhed i labbrock i laboratoriet.
Fredrik Bäckhed får motsvarande 28 miljoner kronor från EU till forskning som kan leda till en ny behandling för både hjärtsvikt och leversjukdom.
Photo: Johan Wingborg

Developing a novel treatment for heart failure


Gut bacteria can form a substance that seems to contribute to stiffening of the heart, liver, and other organs, potentially boosting the risks of heart failure and liver disease. Professor Fredrik Bäckhed has just been awarded a substantial grant from the EU to develop this discovery in the direction of a therapy to stop the bacteria secreting the harmful molecule.

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

Fredrik Bäckhed
Fredrik Bäckhed
Photo: Johan Wingborg

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

A glass container with a brown-yellow liguid, sized like a small football, on lab bench.
Bioreactors serve as a sort of artificial intestine in the lab.
Photo: Nicklas Elmrin

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.

Two researchers at the University of Gothenburg received the ERC Advanced Grant 2022

In addition to Fredrik Bäckhed, one more researcher will receive an ERC Advanced Grant in 2022. It is Randi Hjalmarsson, professor of economics at the School of Business, Economics and Law, who is researching how criminal cycles can be broken.

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