The contribution of genetics to understanding human diseases has made substantial progress in recent decades. However, the role of environmental stressors in disease development remains poorly understood. In 2005, Chris Wild proposed a new concept, the exposome, which refers to the totality of exposures to environmental stressors from conception to death.
This concept aims to integrate different types of exposures, including chemical, physical, biological, and psycho-social stressors, and to consider the temporal dimension. Recently, exosomes have been integrated with other omics, leading to functional exosomes, which characterize the exposome’s biological translation and its multiple exposures.
New research published in the Journal of Hepatology indicates that environmental exposures are significantly associated with liver diseases, paving the way for a more comprehensive understanding of the exposome’s role in the development of this pathology. The exposome concept refers to the totality of exposures an individual experiences throughout their life that may impact their health. This concept has been the subject of much research, including analytical, epidemiological, and toxicological/mechanistic studies that have aimed to characterize the exposome.
However, this research has emphasized the urgent need to link the exposome to human diseases and include exosomes in the characterization of environment-linked pathologies with genomics and other omics. Liver diseases are particularly well suited for such studies since the liver is responsible for detecting, detoxifying, and eliminating xenobiotics and mounting inflammatory responses.
Several liver diseases have been associated with a range of addictive behaviors such as alcohol consumption, smoking, and to a certain extent, dietary imbalance and obesity, viral and parasitic infections, and exposure to toxins and occupational chemicals. More recent studies have indicated that environmental exposures were also significantly associated with liver diseases.
These exposures include air pollution (particulate matter and volatile chemicals), contaminants such as polyaromatic hydrocarbons, bisphenol A, and per-and poly-fluorinated substances, and physical stressors such as radiation. Liver cancer is one of the most common types worldwide, with hepatocellular carcinoma (HCC) and cholangiocarcinoma being the most predominant primary liver cancers. Both types of cancer are usually diagnosed at an advanced stage, which may explain the poor prognosis despite some treatment progress.
HCC is the most frequent liver cancer, and in the vast majority of cases, it develops on the ground of liver cirrhosis after a long evolution of chronic liver disease mainly caused by HBV or HVC infection, alcohol consumption, or toxins like aflatoxins, aristolochic acid and cyanotoxins as well as drugs and occupational chemicals.
In addition, the microbiome metabolites and the “Gut-Liver” axis have been found to play a significant role in developing liver pathology. As such, exposomics is poised to play a significant role in the field of liver pathology, as methodological advances include the exosomes-metabolomics framework, genomics, and epigenomics signatures of risk factors and cross-species biological pathway analysis should further delineate the impact of the exposome on the liver.
These advances in exposomics research are expected to lead to improved prevention strategies, new biomarkers of exposure and effects, and additional therapy targets. Ultimately, integrating exposomics into the study of liver diseases will provide a more comprehensive understanding of the pathophysiology of this condition, which is critical for the development of effective treatments and prevention strategies.
