August 20, 2025

Did you know that your gut microbiota – a community of trillions of bacteria, viruses, and other microorganisms plays a significant role in your liver health? The balance of these microbes can influence various metabolic processes, including those that contribute to liver diseases like Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Previously known as Non-Alcoholic Fatty Liver Disease (NAFLD), MASLD has become one of the most common causes of chronic liver disease worldwide, affecting millions of people.

What is MASLD?

MASLD refers to the accumulation of excess fat in the liver without significant alcohol intake. While some liver fat is normal, too much can trigger inflammation, leading to Metabolic Dysfunction-Associated Steatohepatitis (MASH) – formerly known as Non-Alcoholic Steatohepatitis (NASH). If left untreated, MASH can progress to fibrosis, cirrhosis, or even liver cancer.

What Causes MASLD?

Several factors contribute to MASLD, including:

• Unhealthy Diets: High consumption of processed foods, sugary drinks, and unhealthy fats can lead to liver fat accumulation.
• Sedentary Lifestyle: Physical inactivity and prolonged sitting increase the risk of MASLD.
• Metabolic Disorders: Insulin resistance, obesity, type 2 diabetes, and high cholesterol levels are major risk factors.
• Gut Microbiota Imbalance: An unhealthy gut microbiome, known as dysbiosis, may contribute to inflammation and metabolic dysfunction, further aggravating MASLD.

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How Does MASLD Progress?

Not everyone with risk factors develops the severe form of MASLD. Scientists are still investigating why some individuals progress from simple fat accumulation (steatosis) to more severe liver damage. Research suggests that gut microbiota and its metabolites may play a critical role in determining disease progression.

What current treatments are available?

When this project first began, there were no approved treatments available for MASLD. Since then, progress has been made – most notably, the FDA’s approval of resmetirom in early 2024. However, its use is currently limited to adults with non-cirrhotic MASH and fibrosis stages F2 or F3, and only about a quarter of patients show a clear histological improvement.

At present, there are still no widely approved drug treatments for MASLD. The cornerstone of management remains lifestyle modification, which includes

• Eating a balanced diet with fresh fruits, vegetables, and whole grains.
• Engaging in regular physical activity to prevent fat buildup in the liver.
• Managing metabolic conditions like diabetes and obesity to reduce inflammation.

However, lifestyle changes alone may not be sufficient for all patients, highlighting the need for new therapeutic options.

Afekta’s Role in MASLD Research

Afekta Technologies is an SME partner in the Marie Skłodowska-Curie-funded Innovative Training Network, BestTreat (www.besttreat.eu). This initiative brings together researchers across Europe to implore about MASLD pathogenesis and explore novel MASLD treatments, including innovative gut microbiome interventions.

Key contributions

LC-MS/MS Methods for MASLD-related metabolites

As part of the BestTreat project, we aimed to conduct research on MASLD. A critical step was developing methods to accurately identify MASLD-related metabolites. Since we expected to receive samples from various species and different tissue matrices over the years, we needed a method capable of detecting a broad range of metabolites, including those already reported in literature.

To address this, Afekta validated a simple yet highly sensitive LC-MS/MS (liquid chromatography-tandem mass spectrometry) technique to identify MASLD-related metabolites. This method enables the detection of sterols, bile acids, and acylcarnitines across different species, making it a valuable tool for routine scientific research (DOI: https://doi.org/10.3390/metabo12010049).

Understanding Metabolic Changes in MASLD

With the analytical method in place, we turned to investigate MASLD development and progression, focusing on the metabolic changes occurring at different stages of the disease.

In collaboration with the University of Eastern Finland, Afekta examined metabolic shifts in a diet-induced MASLD mouse model at 8, 12, and 16 weeks. The study uncovered a progressive decline in polyunsaturated fatty acids and a rise in inflammation-associated lipids, providing new insights into the pathogenesis of the disease (DOI: https://doi.org/10.1016/j.jnutbio.2023.109307).

But what about humans? To address this, we analyzed data from human subjects in collaboration with the Kuopio University Hospital, further validating our findings. Key findings revealed a decrease in specific lysophosphatidylcholines (LPC(18:2), LPC(18:3), LPC(20:3)) and an increase in xanthine levels from steatosis to MASH. We also identified distinct metabolic pathways, some independent of insulin resistance and dyslipidemia, offering new insights into the mechanisms driving liver pathology and cardiovascular risk in MASLD (DOI: https://doi.org/10.1016/j.dld.2024.05.015).

Investigating the effects of High-Intensity Interval Training (HIIT) in MASLD

After identifying metabolic changes in MASLD, the next question was how to treat MASLD at different stages. Exercise is well known for its benefits, but what is the mechanism behind the improvements?

Afekta participated in a study evaluating the effects of high-intensity interval training (HIIT) in MASLD subjects in collaboration with the University of Eastern Finland, Kuopio University Hospital, and Kuopio Research Institute of Exercise Medicine. After 12 weeks, we identified distinct metabolic changes in a sample-type specific manner. Notably, lipid metabolism was altered independently of traditional cardiometabolic markers, suggesting that the relative risk reduction in MASLD and CVD with exercise training is not limited to classic markers of cardiometabolic health (DOI: https://doi.org/10.1038/s41598-022-10481-9).

In collaboration with researchers from the University of Amsterdam, the study was extended to MASH patients. HIIT improved cardiorespiratory fitness, reduced visceral fat, and induced beneficial gene expression changes in the muscle, adipose tissue, and liver. Various changes in specific gut microbial taxa and metabolites were also observed. Although no histological improvements were seen in liver steatosis, inflammation, or fibrosis, the results point to the need for longer interventions for histological improvements (DOI: https://doi.org/10.1016/j.jhepr.2024.101289).

Exploring Diet and Engineered Gut Bacteria as a Therapy

Beyond exercise, dietary changes are also known to alleviate MASLD. In collaboration with researchers from the University of Eastern Finland, we observed significant metabolic improvements in a high-fat-diet-induced MASLD mouse model following a switch to a control diet.

However, diet and exercise alone may not be sufficient, highlighting the need for alternative therapies. In collaboration with the Technical University of Denmark and the University of Eastern Finland, Afekta analyzed metabolomics data from MASLD mouse models treated with engineered gut bacteria. One study focused on Escherichia coli Nissle 1917, which was genetically modified to produce Aldafermin, a non-tumorigenic analog of FGF19 – a hormone found to be decreased in MASLD patients. The other study focused on Escherichia coli Nissle 1917, which was genetically modified to produce insulin-like growth factor 1 (IGF1). Results showed positive effects on liver metabolism, induced changes in gut-microbial metabolites, and potentially reduced oxidative stress (DOI: https://doi.org/10.1016/j.molmet.2023.101823, https://doi.org/10.1021/acs.jafc.5c01674).

Investigating the Gut-Liver Connection

Afekta, in collaboration with the University of Groningen, has explored the gut microbiota’s role in MASLD. This research has identified specific metabolites that interact with liver metabolic pathways, further supporting the potential for microbiome-based therapies for MASLD (DOI: https://doi.org/10.1016/j.micres.2024.127700).

The Future of MASLD Research

MASLD is a complex disease influenced by genetics, lifestyle, gut microbiota, etc. A comprehensive approach integrating metabolomics, microbiome research, and advanced diagnostics is essential for better prevention and treatment strategies.

At Afekta Technologies, we are committed to supporting MASLD research. Through our continued efforts, we aim to contribute to advances that help shape the future of liver health.

Stay tuned for more updates and remember, a healthy gut means a healthier liver!

Ambrin Farizah Babu