ABSTRACT: Obesity is a complex chronic, relapsing, progressive disease. Association studies have linked microbiome alterations with obesity and overweight. However, the results are not always consistent. An integrated analysis of 4282 fecal samples (2236 control (normal weight) group, 1152 overweight, and 894 simple obesity) was performed to identify obesity-associated microbial markers. Based on a random effects model and a fixed effects model, we calculated the odds ratios of the metrics, including bacterial alpha-diversity, beta-diversity, Bacteroidetes/Firmicutes ratio, common genera, and common pathways, between the simple obesity and control groups as well as the overweight and control groups. The random forest model was trained based on a single dataset at the genus level. Feature selection based on feature importance ranked by mean decrease accuracy and leave-one-out cross-validation was conducted to improve the predictive performance of the models. Chao1 and evenness possessed significant ORs higher than 1.0 between the obesity and control groups. Significant bacterial community differences were observed between the simple obesity and the control. The ratio of Bacteroidetes/Firmicutes was significantly higher in simple obesity patients. The relative abundance of Lachnoclostridium and Faecalitalea were higher in people with simple obesity, while 23 genera, including Christensenellaceae_R-7_group, Akkermansia, Alistipes, and Butyricimonas, etc., were significantly lower. The random forest model achieved a high accuracy (AUC = 0.83). The adenine and adenosine salvage pathway (PWY-6609) and the L-histidine degradation I pathway (HISDEG-PWY) were clustered in obese patients, while amino acid biosynthesis and degradation pathways (HISDEG-PWY, DAPLYSINESYN-PWY) were decreased. This study identified obesity microbial biomarkers, providing fertile targets for the management of obesity.
