Université Paris Cité, Inserm T3S, Paris, France.
Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France.
J Hepatol. 2023 Aug;79(2):492-505. doi: 10.1016/j.jhep.2023.02.034. Epub 2023 Mar 6.
Since the initial development of the exposome concept, much effort has been devoted to the characterisation of the exposome through analytical, epidemiological, and toxicological/mechanistic studies. There is now an urgent need to link the exposome to human diseases and to include exposomics in the characterisation of environment-linked pathologies together with genomics and other omics. Liver diseases are particularly well suited for such studies since major functions of the liver include the detection, detoxification, and elimination of xenobiotics, as well as inflammatory responses. It is well known that several liver diseases are associated with i) addictive behaviours such as alcohol consumption, smoking, and to a certain extent dietary imbalance and obesity, ii) viral and parasitic infections, and iii) exposure to toxins and occupational chemicals. Recent studies indicate that environmental exposures are also significantly associated with liver diseases, and these 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. Furthermore, microbial metabolites and the "gut-liver" axis play a major role in liver diseases. Exposomics is poised to play a major role in the field of liver pathology. Methodological advances such as the exposomics-metabolomics framework, the determination of risk factors' genomic and epigenomic signatures, and cross-species biological pathway analysis should further delineate the impact of the exposome on the liver, opening the way for improved prevention, as well as the identification of new biomarkers of exposure and effects, and additional therapeutic targets.
自从暴露组概念的最初发展以来,人们已经投入了大量的精力来通过分析、流行病学和毒理学/机制研究来描述暴露组。现在迫切需要将暴露组与人类疾病联系起来,并将暴露组学纳入与基因组学和其他组学一起描述与环境相关的病理学特征中。肝脏疾病特别适合进行此类研究,因为肝脏的主要功能包括检测、解毒和消除外来物质以及炎症反应。众所周知,一些肝脏疾病与以下因素有关:i)成瘾行为,如饮酒、吸烟,在一定程度上还与饮食失衡和肥胖有关;ii)病毒和寄生虫感染;iii)暴露于毒素和职业性化学物质。最近的研究表明,环境暴露也与肝脏疾病密切相关,这些暴露包括空气污染(颗粒物和挥发性化学物质)、多环芳烃、双酚 A 和全氟及多氟化合物等污染物以及辐射等物理应激源。此外,微生物代谢物和“肠道-肝脏”轴在肝脏疾病中起着重要作用。暴露组学有望在肝脏病理学领域发挥重要作用。方法学上的进步,如暴露组学-代谢组学框架、确定风险因素的基因组和表观基因组特征,以及跨物种生物途径分析,应该进一步阐明暴露组对肝脏的影响,为改善预防措施以及识别新的暴露和效应生物标志物以及额外的治疗靶点铺平道路。
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