Distinctive Gut Microbiota in Patients with Overweight and Obesity with Dyslipidemia and its Responses to Long-term Orlistat and Ezetimibe Intervention: A Randomized Controlled Open-label Trial

Abstract

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.

Correlation between Gut Microbiota, its Metabolic Products, and their Association with Liver Enzymes among Sample of Egyptian Females

“…Studies have reported controversial data about the Firmicutes/Bacteroidetes ratio and the proportion of Firmicutes and Bacteroidetes in obesity. The present data were in agreement with many other studies in China [22], United Kingdom [23], and Canada [24] where insignificant differences in Firmicutes to Bacteroidetes ratio was observed between lean and obese individuals, other studies found that the gut microbiota of obese people is characterized by an increase in the Firmicutes/Bacteroidetes ratio; as in Ukraine [25] and Italy [26]; while others even find an opposite relationship; as in China [27].…”

“…Obese females in the present study had insignificant higher values of log Lactobacillus, and insignificant lower values of Bifidobacteria; than normal weight ones. Similarly, a study showed that microbiota composition of overweight and obese adults with dyslipideamia in China was characterized by over representation of Lactobacillus as a counter protective reaction but with reduction of Bifidobacterium [22]. It was also found that gut microflora in obese patients is characterized by greater numbers of Lactobacillus and lesser numbers of Bifidobacteria species [29].…”

Orlistat, a competitive lipase inhibitor used as an antiobesity remedy, enhances inflammatory reactions in the intestine

“…Recent studies have also shown a similar trend in mice together with reduced microbial diversity and richness [8]. Evidence of increased Proteobacteria and decreased Alloprevotella associated with Orlistat therapy in humans has been reported [11].…”

“…Recent reports suggests that Orlistat therapy induces significant modifications to gut microbe population [8] with Actinobacteria and Proteobacteria groups shown to be the most affected. However, some studies suggest these changes were limited to Proteobacteria, a potential marker diagnostic marker of ecological imbalance and disease risk [9], and other bacterial populations of low relative abundance [10,11]. In our previous study, obese mice treated with a HFD underwent two different interventions [12].…”

“…Changes in gut microbial composition during Orlistat treatment was accompanied by a significant reduction in SCFAs in the gut [12]. A human study on the impact of long-term Orlistat treatment revealed a reduction in the abundance of Alloprevotella, an acetic acid-producing bacteria belonging to the Bacteroidetes phylum [11]. These changes suggest an alteration in secondary gut metabolites.…”