Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel diagnostic criterion proposed by an international consensus in 2020, replacing the traditional term "non-alcoholic fatty liver disease (NAFLD)" to emphasize the central role of metabolic dysfunction in disease pathogenesis. Notably, despite increasing public awareness of health issues, MAFLD still affects over 30 % of the global population. Patients with MAFLD frequently exhibit concomitant metabolic abnormalities, including hypertension, dyslipidemia, and insulin resistance [1,2]. The pathogenesis of MAFLD is often linked to disruptions in glucolipid metabolism, including nutritional excess, insulin resistance, and obesity. The adipocyte-derived free fatty acids (FFA) are elevated under the influence of these factors, fueling hepatic lipid overload. Insulin resistance elevates circulating FFA levels via lipolysis, thereby intensifying hepatic steatosis [[3], [4], [5], [6]]. Dyslipidemia, marked by abnormal lipid profiles (elevated triglycerides and LDL, reduced HDL), drives hepatic steatosis while heightening cardiovascular risk [7]. Additionally, it can trigger inflammatory responses that disrupt gut microbiota, directly causing hepatic inflammation and accelerating MAFLD progression. The imbalance in gut microbiota can disrupt liver lipid metabolism and energy homeostasis, acting as a driving mechanism for multi-level MAFLD development [8,9].

Several pharmacological agents are currently available for MAFLD treatment, including insulin sensitizers, antioxidants, fatty acid oxidation inhibitors, and bile acid modulators. However, these treatments often require personalized adjustments and continuous monitoring for potential adverse effects, which can impact patient compliance and treatment efficacy. For those with MAFLD and either diabetes or insulin resistance, metformin is a common treatment, though it might cause stomach discomfort and, in rare instances, lactic acidosis. Vitamin E can mitigate liver oxidative stress and enhance liver function, but prolonged high-dose usage may elevate the risk of prostate cancer and bleeding. Obeticholic acid, a bile acid synthesis inhibitor, may cause itching, fatigue, transient dyslipidemia, and potentially worsen liver injury [[10], [11], [12], [13], [14]]. Clinical practice guidelines have consistently prioritized healthy eating patterns as a key recommendation for improving MAFLD. Furthermore, the consumption of foods rich in dietary functional components that can prevent and ameliorate dyslipidemia holds great promise for treating and preventing metabolic syndrome [[15], [16], [17]]. In managing MAFLD, dietary therapy has gained considerable attention due to its distinct advantages, including fewer side effects and lower costs. As research into the role of dietary functional components in disease treatment continues to evolve, the interactions between gut microbiota and food components are becoming increasingly clear. Specifically, certain dietary components, such as polysaccharides, resistant starches, flavonoids, and polyphenols, can reshape gut microbiota structure and function. Conversely, gut microbiota can influence dietary components through metabolic processes such as fermentation and transformation, thereby regulating the host's metabolism and immune responses [[18], [19], [20], [21]].

Soybean, a high-quality legume, is widely cultivated across diverse climatic regions, including subtropical and temperate zones. As a primary source of plant-based protein, it provides essential nutrients to hundreds of millions globally. Particularly in less developed regions, soybeans serve as an effective and affordable alternative to animal proteins, becoming a staple in local diets. With its low-input and easy-to-manage cultivation, soybeans offer significant economic and environmental benefits. Moreover, soybeans are rich in bioactive components such as isoflavones, soy polysaccharides, unsaturated fatty acids, and various vitamins and minerals, conferring notable health-promoting potential. These functional components enable soybeans to support human health by lowering blood lipids, regulating the endocrine system, and enhancing gut health [[22], [23], [24], [25], [26], [27]]. Among these bioactive compounds, soy isoflavones have attracted particular attention. Research indicates that isoflavones not only improve lipid metabolism and reduce insulin resistance but also play a critical role in endocrine regulation [8,[28], [29], [30]]. Gen, a primary component of soy isoflavones, has shown potential benefits for both the reproductive and cardiovascular systems [8,31,32]. However, despite existing studies on Gen, its effects on MAFLD remain underexplored. Specifically, the impact of Gen-containing foods on the long-term management of MAFLD, especially in relation to its intricate interactions with gut microbiota and SCFAs, has yet to be comprehensively addressed. This study investigates the diverse impacts of Gen intervention on MAFLD rats, emphasizing body weight, insulin resistance, liver function markers, inflammation, oxidative stress, gut microbiota composition and function, and SCFA production. The research focuses on how Gen influences gut microbiota to increase butyrate-mediated activation of SIRT1, thereby improving MAFLD. This lays a theoretical groundwork for using soy - derived Gen as a dietary supplement in MAFLD management.