Exploring the role of exercise in NAFLD
We, early stage researchers at the University of Eastern Finland, are undertaking an exciting research that combines human clinical intervention studies and animal studies to investigate the effects of exercise on Non-Alcoholic Fatty Liver Disease (NAFLD).
Have you ever thought that you can outsource doing physical exercise and enjoy its health benefits? Nowadays, we seem to have a pill for every kind of disease, from headache to diarrhea. However, many chronic diseases still do not have effective therapies and the only way to stay healthy is to live a healthy lifestyle and to exercise. But what if, other people who do exercise can transfer their wholesome health status to you. Sounds very much like science fiction, but we believe by doing physical exercise, one can improve the composition of one’s gut microbiota. And, as the gut microbiome influences our health, by Fecal Microbiota Transplant (FMT) one can transfer such healthy status to others.
Non-Alcoholic Fatty Liver Disease (NAFLD) is an example of chronic disease where there is still a lack of evidence on any approved therapy. NAFLD progresses from simple fatty liver (steatosis) to non-alcoholic steatohepatitis (NASH) characterized by liver inflammation to formation of scar tissue (fibrosis) in liver and then to irreversible replacement of healthy liver tissue with scar tissue (liver cirrhosis) and ultimately liver cancer (hepatocellular carcinoma) and end-stage liver disease.
In Western countries, NAFLD is one of the most common chronic liver diseases, affecting 24% of the world population and 23% of the European population with increasing global prevalence. Imagine, one in 4 of your friends may have NAFLD. NAFLD has also a severe financial effect, the 10-year burden on the European economy and healthcare system is estimated at €334 billion. NAFLD risk factors are a combination of various lifestyle, genetic and environmental factors. Research has shown that NAFLD affects both adults and children with the prevalence of NAFLD being up to 85% in children with obesity. But some individuals with NAFLD are even lean and have normal weight. So, if you think that you are a lean and young teen and don’t need to worry about getting NAFLD, think again. Unhealthy, sedentary lifestyle and increased calorie intake due to prevalence of the western diet consisting of high fat and sugar are still major contributors to rising occurrence of NAFLD. Thus, adopting a healthy diet and taking up regular exercise have great potential to prevent NAFLD and in early stages of reverse its progression. When investigating the NAFLD, our team is focusing on the close relationship between the gut and the liver which we call the gut-liver axis. Our gut is a complex ecosystem where many microorganisms are present, which entirety is called the gut microbiota. The microbiota produces different metabolites, such as short chain fatty acids (SCFAs) which are important fuel for intestinal cells and regulate our immune system. These metabolites can enter our blood stream and eventually reach the liver through the hepatic portal vein. Many researches have shown that a shift in gut microbiota composition and the dominance of only few species is strongly linked to NAFLD. However, the changes in gut microbiota composition and metabolites production during the onset of NAFLD development and whether by re-establishing a healthy gut microbiota can reverse the effects of NAFLD are not understood in detail, which prevents the development of effective guidance and therapy for NAFLD and, thus, new strategies are needed.
To re-establish a healthy gut microbiota, we carry out FMT where faecal bacteria are transplanted from a healthy individual into a recipient at risk of NAFLD. FMT have already been used as therapy for recurrent Clostridium difficile infection with much success and long-lasting effects. Beneficial effects of healthy diet and exercise on obesity have already been shown to be transmissible through FMT in mouse model. FMT in our study can help investigate whether the metabolic benefits of exercise on NAFLD are due to altered gut microbiota and whether such healthy composition of gut microbiota can be transmitted. At the University of Eastern Finland, we follow a practical research approach. During our clinical intervention study, individuals with NAFLD undergo high intensity physical exercise and their fecal samples are collected, which will then be transplanted into mice with NAFLD. The clinical intervention study is already underway, and we are collecting the fecal samples as we speak. At the same time, we are developing the NAFLD mouse model. We are inducing NAFLD in mice by feeding the mice a western diet rich in fat and sugar over a long period of time which mimics the real-life human exposure condition. We are targeting early stages of NAFLD (asymptomatic stages or with minimum symptoms) to avoid the excessive pain characteristic for late stages and the risk of developing cirrhosis and liver cancer. We also applied the 3Rs principle, Replacement, Reduction, Refinement, in our mouse model to minimize any harm done to the animals.
We are very excited to see whether the benefits of physical exercise can be passed on by changing the gut microbiota with FMT which can be a promising targeted therapy for NAFLD. Of course, we are not trying to replace living healthy lifestyle which comes with much more benefits than just changing your gut microbiota. But by complementing a healthy lifestyle with FMT, we hope that individuals with NAFLD can receive a more effective treatment.
Disclaimer: Our research is part of the “Building a Gut Microbiome Engineering Toolbox for In-Situ Therapeutic Treatments for Non-alcoholic Fatty Liver Disease” (BestTreat) programme which is funded by the European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No 813781. All animal studies are operated under licenses for animal experiments approved by the National Animal Experiment Board (Eläinkoelautakunta ELLA).