Leal-Mercado Leonardo, Panduro Arturo, José-Abrego Alexis, Roman Sonia
Department of Genomic Medicine in Hepatology, Civil Hospital of Guadalajara, "Fray Antonio Alcalde", Hospital 278, El Retiro, Guadalajara 44280, Jalisco, Mexico.
Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, Guadalajara 44340, Jalisco, Mexico.
Int J Mol Sci. 2025 Sep 15;26(18):8977. doi: 10.3390/ijms26188977.
Viral hepatitis B and C (HBV and HCV) and metabolic dysfunction-associated steatotic liver disease (MASLD) are major public health concerns in Mexico, driving liver cirrhosis and hepatocellular carcinoma. The Genome-based Mexican (GENOMEX) diet, rich in bioactive compounds, may provide a nutritional strategy for preventing and managing liver disease. This study combines a literature review with integrative bioinformatic analyses to map the antiviral and hepatoprotective mechanisms activated by GENOMEX-derived bioactives and assess their therapeutic potential for preventing and managing liver disease. A literature-based review integrated with bioinformatics to identify the pathways activated by nutrients and bioactive compounds of the GENOMEX diet against HBV, HCV, and MASLD, incorporating data from in silico, in vitro, in vivo, and clinical studies, was conducted. An integrative bioinformatic approach, incorporating the Comparative Toxicogenomic Database and Functional Enrichment Analysis (STRING, DAVID, and Enrichr), was used to identify links between genes, nutrients, and bioactive compounds, with a subset of Mexican food staples included in the GENOMEX diet. The GENOMEX diet includes bioactive nutrients that may modulate molecular pathways related to immune response, oxidative stress, nutrient metabolism, and inflammation. Through integrative analysis, we identified key molecular targets-including TNF, PPARA, TP53, and IL6-that are implicated in viral replication, MASLD progression, and hepatocarcinogenesis. Functional enrichment revealed that these traditional Mexican foods and their nutrients are associated with genes and pathways involved in viral infection, metabolic dysfunction, fibrosis, and liver cancer. These findings highlight that the gene-nutrient interactions of the Mexican staple food in the GENOMEX diet can be integrated into nutritional strategies to prevent and manage HBV, HCV, and MASLD, while reducing fibrosis and HCC progression. These strategies are especially relevant in regions where antiviral treatments are limited due to high costs, antiviral resistance, and an escalating mismatch between the population's evolutionary genetics and modern environment.
乙型和丙型病毒性肝炎（HBV和HCV）以及代谢功能障碍相关脂肪性肝病（MASLD）是墨西哥主要的公共卫生问题，可导致肝硬化和肝细胞癌。富含生物活性化合物的墨西哥基因组（GENOMEX）饮食可能为预防和管理肝病提供一种营养策略。本研究结合文献综述与综合生物信息学分析，以绘制由GENOMEX衍生的生物活性物质激活的抗病毒和肝脏保护机制，并评估其在预防和管理肝病方面的治疗潜力。进行了一项基于文献的综述，并结合生物信息学，以确定GENOMEX饮食中的营养物质和生物活性化合物针对HBV、HCV和MASLD激活的途径，纳入了来自计算机模拟、体外、体内和临床研究的数据。采用一种综合生物信息学方法，纳入比较毒理基因组学数据库和功能富集分析（STRING、DAVID和Enrichr），以确定基因、营养物质和生物活性化合物之间的联系，GENOMEX饮食中包括了一部分墨西哥主食。GENOMEX饮食包括可能调节与免疫反应、氧化应激、营养代谢和炎症相关分子途径的生物活性营养物质。通过综合分析，我们确定了关键分子靶点，包括TNF、PPARA、TP53和IL6，它们与病毒复制、MASLD进展和肝癌发生有关。功能富集表明，这些传统墨西哥食物及其营养物质与参与病毒感染、代谢功能障碍、纤维化和肝癌的基因及途径相关。这些发现突出表明，GENOMEX饮食中墨西哥主食的基因-营养相互作用可纳入营养策略，以预防和管理HBV、HCV和MASLD，同时减少纤维化和HCC进展。这些策略在因成本高、抗病毒耐药性以及人群进化遗传学与现代环境之间日益加剧的不匹配而导致抗病毒治疗有限的地区尤其重要。
