Good examples

Clinical research with translational mindset

Fredrik Bäckhed

Fredrik Bäckhed is a professor in molecular medicine at the University of Gothenburg, and is leading eminent international research on the role of intestinal flora for health and disease. With one foot in the lab and the other at the hospital, he has established a translational function that provides good conditions for patient related research.

Who could only imagine that books about our intestinal flora would be number one on sales lists? Titles like "Gut" and "Clever Gut Diet" have reached a wide audiance and the interest in our intestinal bacteria seems to only increase.

Even in the research community, interest is high. One of those who specializes in how the intestinal flora affects our physiology and its importance for the development of substance-related diseases such as diabetes type 2, obesity and cardiovascular disease, is Fredrik Bäckhed, professor in molecular medicine, as well as director of the Wallenberg Laboratory at the Sahlgrenska Academy.

– The research field has really moved forward. But there is much more to understand, and many unscientific conclusions are drawn that get a lot of public attention. Much advice may apply on a general level, but not always for the individual, and vice versa. One has to distinguish between what has been proven in well-controlled clinical studies and what are case descriptions.

What is a "good" and "bad" intestinal flora, however, can not be answered yet, says Fredrik Bäckhed. But the field of research is hot and development has taken several steps, thanks to new methods in molecular biology and DNA sequencing.

– Somewhat simplified, one might say that a more varied intestinal flora appears to be better than a flora more poor in species.

In the future, Fredrik Bäckhed hopes that with the help of biomarkers, treatments and dietary advice can be designed based on the individual's intestinal flora, which can prevent disease and make us healthier.

– But there is much left to do.

From patient to mouse model

His original plan was to become a high school teacher, but he dropped out and chose to focus on a research career in biomedicine. He defended his thesis on how mucous membranes from different organs recognize bacteria at Karolinska Institutet in 2002. Then he performed postdoctoral research at Washington University in St. Louis, USA, and he has also been a visiting professor in Oslo and Copenhagen.

– I am still involved in research in Copenhagen and we have a strategic research alliance between Gothenburg and Copenhagen University focusing on the intestinal flora.

He has worked and lived in Gothenburg since 2006, and he holds a professorship at Sahlgrenska Academy since 2012.

One important reason for accepting the offer in Gothenburg was the opportunity offered to establish his own research activities with a translational mindset.

– I am not a physician, but I have one foot in the lab and the other at the hospital. It permeates everything we do. In our group, we work closely with physicians and patients in the clinic. The collaboration creates good conditions for clinical trials as we can get important tissue samples and also help formulate and sharpen clinically relevant questions.

Today, research usually starts with an observation of patients in the clinic, and different molecular methods and models are then used to understand and answer questions at the molecular level.

– Previously, we based our questions on mouse models and then tried to verify hypotheses in humans, but now we work mostly the other way around.

Just over two years ago, Fredrik Bäckhed was awarded Torsten Söderberg Academy Professorial Chair in Medicine by the Royal Swedish Academy of Sciences.

– It is very much appreciated and a big recognition for the whole group. In addition, getting a professorship in medicine, even though I'm not a physician, is of course extra stimulating. Our projects usually take a long time and the large funding that we means we can work more in the long term.

Clinical partners

The normal intestinal flora, consisting of ten times more bacteria than human cells in the body, affects our physiology in several ways.

In one of many recognized studies, Fredrik Bäckhed's research group has shown that bacteria-free mice do not develop obesity, so there seems to be a connection between obesity and the intestinal flora. But if it is the intestinal flora that causes obesity or if obesity affects the intestinal flora is not yet clarified.

– My feeling is that the intestinal flora may play a subordinate role in the development of obesity. However, we work on the hypothesis that it can be a factor that protects or leads to the development of type 2 diabetes.

Fredrik Bäckhed talks about some important clinical partners. One of them is Professor Max Nieuwdorp at the Amsterdam Medical Center. The collaboration gives the Gothenburg group access to tissue samples from patients undergoing obesity surgery. The purpose is to investigate how certain intestinal bacteria correlate with certain gene expression.

– Our hypothesis is that the intestinal flora produces molecules that can lead to the development of type 2 diabetes. Through the collaboration, we get access to blood samples taken from the portal vein that lead from the intestine to the liver, as well as tissue samples from the liver, bowel and adipose tissue. In collaboration with Jens Nielsen at Chalmers, we hope to understand which bacteria produce these potentially diabetes-inducing molecules and how they signal in different organs.

Fredrik Bäckhed's research team also works closely with Professor Göran Bergström at SCAPIS (Swedish CardioPulmonary BioImage Study), a world-wide knowledge bank for research. The goal is to be able to detect diseases in the heart, vagina and lungs before they occur. The study is conducted in six university towns in Sweden with the Swedish Heart-Lung Foundation as the main financier.

– Our focus is on diabetes. Together with Göran Bergström here at the Wallenberg Laboratory, we have set up a parallel study to SCAPIS, where we invited thousands of people in the Västra Götaland region to study the intestinal flora in relation to type 2 diabetes. The purpose is to investigate whether important bacteria are missing before individuals develop type 2 diabetes.

Capsule with bacteria

Just over two years ago, Fredrik Bäckhed received a great deal of attention for a study published in Nature Medicine, which showed that the intestinal flora has a key role in treatment with metformin, a classic drug drug that has been around for about 60 years.

By transplanting intestinal flora from patients to bacteria free mice prior to and after metformin treatment, the research team showed that metformin appears to increase the growth of important bacteria, which in turn is linked to improved metabolism and a stable blood sugar.

– Today, approximately 10-15 percent of patients treated with metformin have side effects and 10-15 percent can not continue metmorfin treatment. It would be a great success if we could identify those patients who do not get good treatment results from metformin and adjust their intestinal flora in order to increase treatment results and avoid side effects.

In a future dream scenario, it would be possible to identify people who lack important bacteria and are in danger of developing type 2 diabetes early on, and supply these bacteria in a capsule in order to prevent disease and avoid drug treatment.