This study investigated the gut microbiota and
short chain fatty acids (SCFAs) characteristics of subjects with
obesity from Xinjiang in northwestern China, a region with a multiethnic culture and characteristic lifestyle, and to explore the potential microbes that respond to a 12-wk medication of
orlistat and
ezetimibe with a randomized controlled open-label trial manner. The gut microbiota profile of patients with
overweight and
obesity with
dyslipidemia in Xinjiang was distinctive and characterized by enrichment of Lactobacillus and the reduction of the diversity and the depletion of Actinobacteria, Bacteroides, Bifidobacterium, and Bacteroides fragilis. Prevotella-type, Gemmiger-type, and Escherichia/Shigella-type were the gut microbial patterns of the Xinjiang population. However, the fecal SCFAs levels and enterotypes were similar between healthy individuals and patients. These results indicated that the contribution of the gut microbiota to
obesity was highly dependent on geography and dietary habits. Waist circumference, total
triglyceride (TG), and fasting
blood glucose (FBG) were significantly decreased after
orlistat therapy, whereas TG, total
cholesterol (TC), and
low density lipoprotein cholesterol (
LDL-C) were significantly decreased by
ezetimibe. Overall, the gut microbiota and their SCFAs metabolites were relatively stable
after treatment with the two drugs, with alteration of some low-abundant bacteria, i.e., significantly increased Proteobacteria and decreased Alloprevotella after
orlistat, and increased Fusobacteria and Fusobacterium after
ezetimibe therapy. These results indicated that intestinal malabsorption of
dietary fat and
cholesterol caused by
orlistat and
ezetimibe had a limited effect on the overall gut microbial community and their metabolites. Nevertheless, significant correlations between several core microbes that responded to the medications and biochemical data were found; in particular, Actinomyces and Bacteroides were positively correlated with FBG after
orlistat intervention, while Clostridium XVIII and Lachnospiracea incertae sedis were negatively correlated with TC and
LDL-C after
ezetimibe intervention, thus indicating their roles in improving glucolipid metabolism in
obesity by acting as potential microbial targets.