| More and more evidences have shown that gut microbiota(GM)dysbiosis has been considered as a pathogenic origin of obesity and many related chronic metabolic diseases.In our previous dietary interventional clinical trial,shifted GM structure caused by complex fiber-rich diet was associated with the health improvement of Prader-Willi syndrome(PWS)genetic obese children.The pre-and post-intervention GMs from one PWS child were then transplanted into two germ-free mice,called pre-and post-group,respectively.Compared with the post-group,the pre-group inoculated with the pre-intervention dysbiotic GM from the same PWS child had higher inflammation level and more lipid accumulation.This study investigated the expressions of miRNAs and genes in the 2nd and the 4th week after GM transplantation in colon and liver of these two groups of mice using RNA-seq technology.Taking the post-group as the reference,the pre-intervention dysbiotic GM induced different expressions of miRNAs and genes in the pre-group,and the differentially expressed(DE)miRNAs and genes majorly appeared in the 2nd week.Most of significantly enriched GO biological processes and KEGG pathways were observed in liver in the 2nd week.We screened 23 key genes along with their 73 miRNA regulators relevant to the host phenotype changes and constructed a miRNA-gene-biological function network under the pressure of a dysbiotic GM.The network contained 92 miRNA-gene regulation relationships,51 of which were positive whereas 41 were negative.The dysbiotic GM up-regulated pro-inflammatory genes in both colon and liver and down-regulated genes involved in fatty acid oxidation,lipolysis and plasma cholesterol clearance only in liver,via miRNA expression regulation.These changes were consistent with the host lipid and cholesterol accumulation and the high inflammation level occurred.In addition,the colon showed disordered glucagon-like peptide 1(GLP-1)signaling pathway while the liver displayed decreased insulin receptor signaling pathway.This study provides fundamental molecular information elucidating how a dysbiotic GM increases host inflammation and disturbs host lipid and glucose metabolisms. |
