The Effects Of L-Fucose On High-fat Diet-induced Non-alcoholic Fatty Liver Disease And Gut Microbiota Dysbiosis

BackgroundGut microbiota plays a critical part in body health maintaining,and dysbiosis of the gut microbiota will promote the occurrence and development of the disease.Long-term high-fat diet can cause the dysbiosis of host gut microbiota,which induces the occurrence of non-alcoholic fatty liver disease.With the rapid development of next-generation sequencing technology,it helps human to get a better perspective on gut microbiota and disease.Based on the next-generation sequencing data,targeting gut microbiota,it has the great important directive significance to explore the relationship of the gut microbiota and non-alcoholic fatty l:iver disease.ObjectiveUsing next-generation sequence and relevant bioinformatics analysis,the statistically significant genes were screened from the gut microbiota between normal chow diet mice and high-fat diet mice,to explore the effect of it on high-fat diet-induced non-alcoholic fatty liver disease and gut microbiota dysbiosis in mice.MethodsExperiment 1:The five-week-old C57BL/6 mice were randomly divided into normal chow diet group(fed a low-calorie diet)and high-fat diet group(fed a high-calorie diet).All mice were anesthetized and sacrificed after 18 weeks,and then the cecal microbial DNA were extracted and performed the metagenomic analysis.Experiment 2:The five-to six-week-old C57BL/6 mice were randomly divided into three groups,(1)normal chow diet(NC)group,fed a low-calorie diet;(2)high-fat diet(HFD)group,fed a high-calorie diet;(3)high-fat diet + L-Fucose(HFD + Fuc)group,fed a high-calorie diet,and administered intragastrically with Fuc(0.3 g/kg)once a day from the 8th week until the end of experiment.Meanwhile,mice in the NC and HFD group were administered intragastrically with an identical dose of sterile ddH2O.Glucose tolerance test was performed at 15 weeks and insulin tolerance test was performed at 16 weeks.At the end of the experiment,the tissues were preserved and tested.Cecal microbial DNA were extracted and performed the 16S ribosomal RNA(16S rRNA)gene sequencing.ResultsResult 1:Metagenomic analysis showed that HFD altered the genomic profile of gut microbiota in mice.According to the filter criteria,the Alpha-L-fucosidase(fuca)gene was markedly reduced in the HFD group compared with that in the NC group.The fuca gene in NC group was 1.33 times higher than that of HFD group,and the difference of it was the most significant between the two group(p = 0.0047),and so we focus on fuca gene.Meanwhile,alpha-L-fucosidase(FUCA)is the product of fuca gene expression,and the FUCA catalytically produces L-Fucose.Results 2:Compared to HFD group,the mice in HFD + Fuc group reduced body weight gain,decreased accumulation of epididymal fat,mesenteric fat and subcutaneous fat,declined hepatic triglyceride levels and ameliorated hepatic steatosis.In addition,16S rRNA gene sequence analysis showed that L-Fucose decreased the levels of endotoxin-producing bacteria of the Desulfovibrionaceae family and partly restored HFD-induced enteric dysbiosis at both compositional and functional levels in the mice.ConclusionOur findings suggested that Fuc might be a novel strategy to treat HFD-induced non-alcoholic fatty liver disease and gut microbiota dysbiosis.