Structural modulation of the gut microbiota and the relationship with body weight: compared evaluation of liraglutide and saxagliptin treatment

The mechanisms underlying the weight-loss effect of GLP-1 receptor agonists need further elucidation. The present study was performed to explore the effects of liraglutide and saxagliptin on the composition of the gut microbiota. Mice were randomly treated with saxagliptin or liraglutide for eight weeks. Their metabolic profiles were assessed, and 454 pyrosequencing of 16s rRNA of faeces was performed. Liraglutide induced a smaller body weight gain in mice. The pyrosequencing showed that liraglutide, but not saxagliptin, substantially changed the overall structure of the gut microbiota as well as the relative abundance of weight-relevant phylotypes. Subsequent ridge regression analyses indicated that, in addition to food intake (beta = -0.182, p = 0.043 in phylotypes inversely correlated with body weight) and blood glucose level (beta = -0.240, p = 0.039 in phylotypes positively correlated with body weight), the administration of liraglutide was another independent factor associated with the abundance of weight-relevant phylotypes (beta = 0.389, p = 6.24e-5 in inversely correlated ones; beta = -0.508, p = 2.25e-5 in positively correlated ones). These results evidenced that GLP-1 receptor agonist liraglutide could modulate the composition of the gut microbiota, leading to a more lean-related profile that was consistent with its weight-losing effect.