ena-STUDY-OXFORD-13-10-2020-09:03:25:236-254
Shotgun metagenomics sequences of gut microbiome from obese rats treated with a panel of weight loss drugs
Obesity, metabolic disease and some psychiatric conditions are associated with changes to fecal microbiomes but precisely which bacterial species and specific genes contribute to good health requires deep shotgun sequencing.Using shotgun metagenomics, the composition of the microbiome was obtained for two cohorts of obese female Wistar rats (n=10-12) maintained on a high fat diet before and after a 42-day treatment with a panel of four drugs, alone or in combination: RCOB, bupropion, naltrexone and sibutramine. Consistent weight loss was only observed with sibutramine (5mg/kg po) which acted through reduction of food intake. The composition of microbiome changes over time in line with the phenotype, showing increased beta diversity, a higher Bacteriodetes to Firmicutes ratio, and highly significant changes in species belonging to the Bacteroidetes phylum. In addition, we identify 1047 differentially abundant genes from the whole population which reflect the change in the overall composition of the microbiome, as well as a significant decrease in a panel of genes involved in flagellum assembly and composition.This study provides a large resource comprising complete shotgun metagenomics datasets of the fecal microbiome coupled with weight change and food intake at day 3, day 15 and day 42 from 82 obese rats treated with a range of compounds used for weight loss, which are available to the community for detailed analysis. Furthermore, by conducting a detailed analysis of the microbiome associated with sibrutamine-induced weight loss, we identify changes in specific species and gene groups over time.
Obesity, metabolic disease and some psychiatric conditions are associated with changes to fecal microbiomes but precisely which bacterial species and specific genes contribute to good health requires deep shotgun sequencing.Using shotgun metagenomics, the composition of the microbiome was obtained for two cohorts of obese female Wistar rats (n=10-12) maintained on a high fat diet before and after a 42-day treatment with a panel of four drugs, alone or in combination: RCOB, bupropion, naltrexone and sibutramine. Consistent weight loss was only observed with sibutramine (5mg/kg po) which acted through reduction of food intake. The composition of microbiome changes over time in line with the phenotype, showing increased beta diversity, a higher Bacteriodetes to Firmicutes ratio, and highly significant changes in species belonging to the Bacteroidetes phylum. In addition, we identify 1047 differentially abundant genes from the whole population which reflect the change in the overall composition of the microbiome, as well as a significant decrease in a panel of genes involved in flagellum assembly and composition.This study provides a large resource comprising complete shotgun metagenomics datasets of the fecal microbiome coupled with weight change and food intake at day 3, day 15 and day 42 from 82 obese rats treated with a range of compounds used for weight loss, which are available to the community for detailed analysis. Furthermore, by conducting a detailed analysis of the microbiome associated with sibrutamine-induced weight loss, we identify changes in specific species and gene groups over time.