Microbiome-based treatments to target liver disease
Non-alcoholic fatty liver disease (NAFLD) is estimated to affect almost 25 % of the global population and imposes an enormous burden on European healthcare systems. Risk factors include poor diet, lack of exercise, being overweight and other metabolic disorders such as type 2 diabetes. Having an imbalance in gut microbiome composition, together with related problems concerning intestinal permeability, have also been identified by researchers as possible causal factors. “NAFLD is a silent disease that can develop into severe liver damage,” notes BestTreat coordinator Gianni Panagiotou from the Hans Knöll Institute in Germany. “It is also thought to be a major cause of liver cancer.” Key challenges to tackling this disease include the fact that NAFLD can have a number of root causes and can progress differently depending on the individual. It is therefore not always easy to target therapies to individual needs.
Gut microbiome and liver disease
BestTreat, which was undertaken with the support of the Marie Skłodowska-Curie Actions programme, sought to address this challenge by developing new diagnostic and therapeutic approaches to NAFLD. To do so, the project focused on better understanding the role of the gut microbiome. Interactions between microbiome alterations and inflammation in patients with NAFLD were studied. “One of the first milestones we achieved was discovering gut microbial strains, metabolites and biochemical parameters that could help us predict the risk of developing NAFLD,” says Panagiotou. “To do this, we measured several clinical parameters and blood metabolites and analysed the composition of intestinal microflora in stool samples from NAFLD patients. These were then compared with those of healthy people.” The team also looked at the impact of exercise and prebiotic diets on disease susceptibility and progression in NAFLD patients. The team was able to identify parameters or biomarkers that could help medical staff monitor the progress of such interventions.
AI-based risk assessment methods
One of the most significant results to come out of this work on the microbiome has been the development of an NAFLD risk assessment model based on machine learning. The ultimate goal is for this to eventually replace expensive and invasive liver biopsy procedures. “We hope that our risk assessment model serves as a proof of concept for developing highly accurate AI tools for diagnosing NAFLD,” remarks Panagiotou. “Instead of liver biopsy-based predictions, this tool could enable prognosis and therapy delivery at a population level.” The team also achieved breakthroughs in characterising metabolic changes in NAFLD patients due to physical exercise and a change of diet. “Through clinical trials with NAFLD patients, we were able to identify how a diet rich in prebiotics can improve the prognosis of NAFLD patients,” adds Panagiotou. Simple lifestyle interventions – such as exercise and prebiotic diets – have therefore been shown to have potential as non-invasive, inexpensive and patient-centred therapies.
Fungal strains and NAFLD progression
Other important findings were made. These include the fact that pro-inflammatory genes and mycobiome dysbiosis (an imbalance of fungal strains in the gut) could act together and worsen NAFLD progression. “Although further studies are needed, we found that intestinal fungi play an important and hitherto ignored role in the pathogenesis of NAFLD,” says Panagiotou. The success of BestTreat has therefore opened up new possible avenues of research when it comes to NAFLD, a disease that continues to take a heavy toll on the health of millions of Europeans.
Keywords
BestTreat, liver, microbiome, NAFLD, disease, gut, AI, fungal, mycobiome
