Project description
Gut microbial signals in fatty and autoimmune liver disease
One of the major complications of obesity is fatty liver disease, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). Primary sclerosing cholangitis (PSC) is a rare autoimmune disease affecting the bile ducts. Both may occur in people with inflammatory bowel disease, underscoring the role of the gut microbiome in their development. Interestingly, MASLD and PSC seldom co-occur, which suggests that specific signals from the gut microbiome may promote the development of one condition while simultaneously conferring protection against the other. The ERC-funded FatVersusBile project will investigate how microbial activity influences liver inflammation and fat accumulation. Researchers will use patient samples and advanced microbiome models to uncover microbial drivers as well as fuel the development of improved diagnostics and new therapies.
Objective
The obesity epidemic has caused a surge of metabolic-dysfunction associated steatotic liver disease (MASLD), an important cause of morbidity and mortality. This also leads to other liver diseases presenting with steatotic (fatty) liver as a “second hit”, with unpredictable impact on clinical outcome.
In the present project, I will use the co-existence of two different liver diseases to study how the gut microbiome interacts with steatosis and autoimmunity. Both MASLD and primary sclerosing cholangitis (PSC), an autoimmune disease of the bile ducts, are more common in inflammatory bowel disease (IBD) than in the population, suggesting they are driven by gut microbial activity (gut signals). However, MASLD and PSC co-exist less frequently than expected, appearing to protect against each other. Separate gut signals could therefore influence these conditions, and a driver of one disease could even protect against the other. Studies of PSC-MASLD-IBD provide a unique window to define how gut signals interact to cause and drive liver health, which would be of great importance in MASLD and PSC, where few effective therapies are available.
I have in the ongoing ERC Starting Grant StopAutoimmunity shown that PSC is associated with large changes in microbial functions, motivating the novel hypothesis that distinct gut-derived signals drive autoimmunity of the bile ducts and steatotic liver disease. I will use an extensive set of methods established in my group to define the gut signals acting in PSC and MASLD and liver health. I have available unique cohorts and materials from these conditions, and experimental models based on human microbiome. The expected outcomes include the first detailed description of this clinical problem and the identification of distinct gut signals driving and protecting against steatosis and biliary autoimmunity, serving as basis for diagnostic and prognostic tools, and new targets relevant for trials to prevent and treat liver disease.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography mortality
- natural sciences biological sciences microbiology
- medical and health sciences health sciences nutrition obesity
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2024-COG
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0313 Oslo
Norway
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