Laboratory of Gnotobiology, Institute of Microbiology, Czech Academy of Sciences, 549 22 Novy Hradek, Czech Republic.
Nutrients. 2024 Oct 30;16(21):3722. doi: 10.3390/nu16213722.
: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem closely linked to dietary habits, particularly high fructose consumption. This study investigates the combined effects of fructose and common food preservatives (sodium benzoate, sodium nitrite, and potassium sorbate) on the development and progression of MASLD. : We utilized a human microbiota-associated mouse model, administering 10% fructose with or without preservatives for 11 weeks. Liver histology, hepatic gene expression (microarray analysis), biochemical markers, cytokine profiles, intestinal permeability, and gut microbiome composition (16S rRNA and Internal Transcribed Spacer (ITS) sequencing) were evaluated. : Fructose and potassium sorbate synergistically induced liver pathology characterized by increased steatosis, inflammation and fibrosis. These histological changes were associated with elevated liver function markers and altered lipid profiles. The treatments also induced significant changes in both the bacterial and fungal communities and disrupted intestinal barrier function, leading to increased pro-inflammatory responses in the mesenteric lymph nodes. Liver gene expression analysis revealed a wide range of transcriptional changes induced by fructose and modulated by the preservative. Key genes involved in lipid metabolism, oxidative stress, and inflammatory responses were affected. : Our findings highlight the complex interactions between dietary components, gut microbiota, and host metabolism in the development of MASLD. The study identifies potential risks associated with the combined consumption of fructose and preservatives, particularly potassium sorbate. Our data reveal new mechanisms that are involved in the development of MASLD and open up a new avenue for the prevention and treatment of MASLD through dietary interventions and the modulation of the microbiome.
代谢相关脂肪性肝病（MAFLD）是一个日益严重的全球性健康问题，与饮食习惯密切相关，尤其是高果糖的摄入。本研究探讨了果糖和常见食品防腐剂（苯甲酸钠、亚硝酸钠和山梨酸钾）联合作用对 MAFLD 发展和进展的影响。
我们使用了一种人微生物群相关的小鼠模型，用 10%的果糖和/或防腐剂喂养 11 周。评估了肝脏组织学、肝基因表达（微阵列分析）、生化标志物、细胞因子谱、肠道通透性和肠道微生物群组成（16S rRNA 和内部转录间隔区（ITS）测序）。
果糖和山梨酸钾协同诱导肝脏病理改变，表现为脂肪变性、炎症和纤维化增加。这些组织学变化与肝功能标志物升高和脂质谱改变有关。这些处理还导致细菌和真菌群落的显著变化，并破坏了肠道屏障功能，导致肠系膜淋巴结中促炎反应增加。肝基因表达分析显示，果糖诱导的广泛转录变化受防腐剂的调节。涉及脂质代谢、氧化应激和炎症反应的关键基因受到影响。
我们的研究结果强调了饮食成分、肠道微生物群和宿主代谢在 MAFLD 发展中的复杂相互作用。该研究确定了与果糖和防腐剂联合摄入相关的潜在风险，特别是山梨酸钾。我们的数据揭示了新的机制，这些机制涉及 MAFLD 的发展，并为通过饮食干预和微生物组的调节预防和治疗 MAFLD 开辟了新的途径。
