Yan Yan, Zhang Ke, Li Fanqin, Lin Lishan, Chen Hanzu, Zhuo Lai-Bao, Xu Jinjian, Jiang Zengliang, Zheng Ju-Sheng, Chen Yu-Ming
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China.
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
Hepatobiliary Surg Nutr. 2025 Feb 1;14(1):16-32. doi: 10.21037/hbsn-23-526. Epub 2024 Jul 15.
Many studies have shown that carotenoids are beneficial to non-alcoholic fatty liver disease (NAFLD). Therefore, we explored potential biomarkers of gut microbiota and fecal and serum metabolites linking the association between serum carotenoids and NAFLD in adults.
This 7.8-year prospective study included 2921 participants with serum carotenoids at baseline and determined NAFLD by ultrasonography (ULS-NAFLD) every 3 years. A total of 828 subjects additionally underwent magnetic resonance imaging to identify NAFLD (MRI-NAFLD). Gut microbiota was analyzed by 16S rRNA sequencing in 1,661 participants, and targeted metabolomics profiling in 893 feces and 896 serum samples was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in the middle term.
A total of 2,522 participants finished follow-up visits. Of these participants, 770, 301, 474, and 977 were categorized into NAFLD-free, improved, new-onset, and persistent NAFLD groups based on their ULS-NAFLD status changes, respectively, and 342/828 were MRI-verified NALFD. Longitudinal analyses showed an inverse association between carotenoids and NALFD risk/presence (P <0.05). Multivariable-adjusted odds ratios (ORs)/hazard ratio (HR) [95% confidence intervals (CIs)] of NAFLD for quartile 4 ( quartile 1) of total carotenoids were 0.63 (0.50, 0.80) for incident ULS-NAFLD, 0.20 (0.15, 0.27) for persistent ULS-NAFLD, 1.53 (1.10, 2.12) for improved-NAFLD, and 0.58 (0.39, 0.87) for MRI-NAFLD. The biomarkers in the gut-liver axis significantly associated with both serum carotenoids and NAFLD included sixteen microbial genera mainly in and family, nineteen fecal metabolites containing medium-chain fatty acids (MCFAs), bile acids, and carnitines, and sixteen serum metabolites belonging to organic acids and amino acids. The total carotenoids-related scores of significant microbial genera, fecal and serum metabolites mediated the carotenoids-NAFLD association by 8.72%, 12.30%, and 16.83% (all P<0.05) for persistent NAFLD and 9.46%, 8.74%, and 15.7% for incident-NAFLD, respectively.
Our study reveals a beneficial association of serum carotenoids and incident and persistent NAFLD. The identified gut-liver axis biomarkers provided mechanistic linkage for the epidemiological association.
许多研究表明，类胡萝卜素对非酒精性脂肪性肝病（NAFLD）有益。因此，我们探索了肠道微生物群以及粪便和血清代谢物的潜在生物标志物，以阐明血清类胡萝卜素与成人NAFLD之间的关联。
这项为期7.8年的前瞻性研究纳入了2921名基线时检测血清类胡萝卜素的参与者，并每3年通过超声检查（ULS-NAFLD）确定NAFLD情况。另外828名受试者接受了磁共振成像以确定NAFLD（MRI-NAFLD）。对1661名参与者进行16S rRNA测序分析肠道微生物群，并在中期通过超高效液相色谱-串联质谱（UPLC-MS/MS）对893份粪便和896份血清样本进行靶向代谢组学分析。
共有2522名参与者完成随访。在这些参与者中，根据他们的ULS-NAFLD状态变化，分别有770、301、474和977人被归类为无NAFLD、改善、新发和持续性NAFLD组，并且342/828例为MRI确诊的NALFD。纵向分析显示类胡萝卜素与NALFD风险/存在呈负相关（P<0.05）。总类胡萝卜素四分位数4（四分位数1）的NAFLD多变量调整比值比（OR）/风险比（HR）[95%置信区间（CI）]，对于新发ULS-NAFLD为0.63（0.50，0.80），对于持续性ULS-NAFLD为0.20（0.15，0.27），对于改善型NAFLD为1.53（1.10，2.12），对于MRI-NAFLD为0.58（0.39，0.87）。肠道-肝脏轴中的生物标志物与血清类胡萝卜素和NAFLD均显著相关，包括主要在 科和 科中的16个微生物属、19种含有中链脂肪酸（MCFA）、胆汁酸和肉碱的粪便代谢物，以及16种属于有机酸和氨基酸的血清代谢物。对于持续性NAFLD，显著微生物属、粪便和血清代谢物的总类胡萝卜素相关评分分别介导类胡萝卜素-NAFLD关联的8.72%、12.30%和16.83%（均P<0.05），对于新发NAFLD分别为9.46%、8.74%和15.7%。
我们的研究揭示了血清类胡萝卜素与新发和持续性NAFLD之间的有益关联。所确定的肠道-肝脏轴生物标志物为这种流行病学关联提供了机制联系。
