Cohen Catherine C, Huneault Helaina, Accardi Carolyn J, Jones Dean P, Liu Ken, Maner-Smith Kristal M, Song Ming, Welsh Jean A, Ugalde-Nicalo Patricia A, Schwimmer Jeffrey B, Vos Miriam B
Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA.
Metabolites. 2023 Mar 8;13(3):401. doi: 10.3390/metabo13030401.
Dietary sugar reduction is one therapeutic strategy for improving nonalcoholic fatty liver disease (NAFLD), and the underlying mechanisms for this effect warrant further investigation. Here, we employed metabolomics and metagenomics to examine systemic biological adaptations associated with dietary sugar restriction and (subsequent) hepatic fat reductions in youth with NAFLD. Data/samples were from a randomized controlled trial in adolescent boys (11-16 years, mean ± SD: 13.0 ± 1.9 years) with biopsy-proven NAFLD who were either provided a low free-sugar diet (LFSD) ( = 20) or consumed their usual diet ( = 20) for 8 weeks. Plasma metabolomics was performed on samples from all 40 participants by coupling hydrophilic interaction liquid chromatography (HILIC) and C chromatography with mass spectrometry. In a sub-sample ( = 8 LFSD group and = 10 usual diet group), 16S ribosomal RNA (rRNA) sequencing was performed on stool to examine changes in microbial composition/diversity. The diet treatment was associated with differential expression of 419 HILIC and 205 C metabolite features ( < 0.05), which were enriched in amino acid pathways, including methionine/cysteine and serine/glycine/alanine metabolism ( < 0.05), and lipid pathways, including omega-3 and linoleate metabolism ( < 0.05). Quantified metabolites that were differentially changed in the LFSD group, compared to usual diet group, and representative of these enriched metabolic pathways included increased serine ( = 0.001), glycine ( = 0.004), 2-aminobutyric acid ( = 0.012), and 3-hydroxybutyric acid ( = 0.005), and decreased linolenic acid ( = 0.006). Microbiome changes included an increase in richness at the phylum level and changes in a few genera within . In conclusion, the LFSD treatment, compared to usual diet, was associated with metabolome and microbiome changes that may reflect biological mechanisms linking dietary sugar restriction to a therapeutic decrease in hepatic fat. Studies are needed to validate our findings and test the utility of these "omics" changes as response biomarkers.
减少膳食糖摄入是改善非酒精性脂肪性肝病（NAFLD）的一种治疗策略，这种效应的潜在机制值得进一步研究。在此，我们运用代谢组学和宏基因组学来研究与NAFLD青少年膳食糖限制及（随后的）肝脏脂肪减少相关的全身生物学适应性变化。数据/样本来自一项针对经活检证实患有NAFLD的青春期男孩（11 - 16岁，平均±标准差：13.0±1.9岁）的随机对照试验，这些男孩被分为两组，一组给予低游离糖饮食（LFSD）（n = 20），另一组维持其常规饮食（n = 20），为期8周。通过亲水相互作用液相色谱（HILIC）和C色谱与质谱联用，对所有40名参与者的样本进行血浆代谢组学分析。在一个子样本（8名LFSD组和10名常规饮食组）中，对粪便进行16S核糖体RNA（rRNA）测序，以检测微生物组成/多样性的变化。饮食治疗与419个HILIC和205个C代谢物特征的差异表达相关（P < 0.05），这些特征在氨基酸途径中富集，包括甲硫氨酸/半胱氨酸和丝氨酸/甘氨酸/丙氨酸代谢（P < 0.05），以及脂质途径，包括ω-3和亚油酸代谢（P < 0.05）。与常规饮食组相比，LFSD组中差异变化且代表这些富集代谢途径的定量代谢物包括丝氨酸增加（P = 0.001）、甘氨酸增加（P = 0.004）、2-氨基丁酸增加（P = 0.012）和3-羟基丁酸增加（P = 0.005），以及亚麻酸减少（P = 0.006）。微生物组变化包括门水平上丰富度的增加以及拟杆菌门内一些属的变化。总之，与常规饮食相比，LFSD治疗与代谢组和微生物组的变化相关，这些变化可能反映了将膳食糖限制与肝脏脂肪治疗性减少联系起来的生物学机制。需要开展研究来验证我们的发现，并测试这些“组学”变化作为反应生物标志物的效用。
