Background: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 a...Background: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.Methods: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.Results: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-trend<0.05).Multivariable-adjusted odds ratios(ORs)/hazard ratio(HR)[95%confidence intervals(CIs)]of NAFLD for quartile 4(vs.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 Ruminococcaceae and Veillonellaceae 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.Conclusions: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.展开更多
文摘Background: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.Methods: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.Results: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-trend<0.05).Multivariable-adjusted odds ratios(ORs)/hazard ratio(HR)[95%confidence intervals(CIs)]of NAFLD for quartile 4(vs.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 Ruminococcaceae and Veillonellaceae 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.Conclusions: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.
