Challenge

Metabolic dysfunction-associated steatotic liver disease (MASLD), a growing global health concern, is influenced by complex interactions between genetic, lifestyle, and environmental factors. Among these, exposure to endocrine-disrupting chemicals (EDCs) is suspected to significantly contribute to disease onset and progression, yet the exact causal mechanisms and internal biological pathways remain poorly understood. Additionally, there is limited data on how EDC mixtures interact with other variables, such as diet, medications, infections, or stress, to worsen liver damage.

Solutions

EDC-MASLD aims to uncover how environmental exposure to EDCs affects the internal exposome, encompassing the metabolome, gut microbiome, epigenome, proteome, and immunome, and contributes to the progression of MASLD. Through prospective multi-omics clinical studies, the project investigates this relationship during critical transitions to more advanced stages of liver disease. A complementary focus on mechanistic research uses murine and zebrafish MASLD models, as well as 2D and 3D human in vitro systems, to examine how EDCs cause hepatic injury and influence disease resolution. EDC-MASLD also advances computational biology by developing an integrative system and high-throughput screening platform. This includes tools such as Adverse Outcome Pathways (AOPs) and genome-scale metabolic modelling, enabling the study of EDCs and their mixtures with broad applicability beyond MASLD. Finally, the project engages with affected communities to identify socioeconomic, lifestyle, and behavioural factors associated with higher EDC exposure. It also gauges public attitudes toward the removal of harmful EDCs from consumer markets, offering support for policy action under EU chemicals legislation.

Results

EDC-MASLD’s findings will significantly deepen the scientific understanding of how EDCs contribute to liver disease, potentially transforming risk assessment and regulatory processes in environmental health. By linking environmental exposure to molecular and clinical outcomes in MASLD, the project will pave the way for earlier detection, targeted prevention strategies, and personalised interventions. The insights gained can inform EU public health and environmental policies, especially those aiming to restrict or eliminate harmful chemical exposures. Furthermore, the systems biology platform developed within the project has long-term value for studying other environment-related chronic diseases, amplifying the project’s impact beyond liver health.