A Glucagon-Like Peptide-1 Receptor Agonist Lowers Weight by Modulating the Structure of Gut Microbiota

Abstract

In addition to improving glucose metabolism, liraglutide, a glucagon-like peptide-1 receptor agonist, has weight-loss effects. The underlying mechanisms are not completely understood. This study was performed to explore whether liraglutide could lower weight by modulating the composition of the gut microbiota in simple obese and diabetic obese rats. In our study, Wistar and Goto-Kakizaki (GK) rats were randomly treated with liraglutide or normal saline for 12 weeks. The biochemical parameters and metabolic hormones were measured. Hepatic glucose production and lipid metabolism were also assessed with isotope tracers. Changes in gut microbiota were analyzed by 16S rRNA gene sequencing. Both glucose and lipid metabolism were significantly improved by liraglutide. Liraglutide lowered body weight independent of glycemia status. The abundance and diversity of gut microbiota were considerably decreased by liraglutide. Liraglutide also decreased obesity-related microbial phenotypes and increased lean-related phenotypes. In conclusion, liraglutide can prevent weight gain by modulating the gut microbiota composition in both simple obese and diabetic obese subjects.

Probiotic Mixture of Lactobacillus plantarum Strains Improves Lipid Metabolism and Gut Microbiota Structure in High Fat Diet-Fed Mice

“…At the genus level, our results reflected that the relative abundances of Bifidobacterium, Bacteroides, Alistipes, Lachnospiraceae NK4A136 group and Alloprevotella decreased while that of Parabacteroides, Eubacterium xylanophilum group, GCA-900066575, Lachnoclostridium, Lachnospiraceae UCG-006 and Romboutsia increased in the HFD group compared with the control group. In line with our results, earlier studies found that the abundances of Bifidobacterium (Zhu et al, 2018), Bacteroides (Zhang et al, 2015;Martinez et al, 2017), Alistipes (Zhu et al, 2018), Lachnospiraceae NK4A136 group , and Alloprevotella were negatively correlated with obesity, and the abundances of Parabacteroides (Lieber et al, 2018;Zhao et al, 2018), Eubacterium xylanophilum group , GCA-900066575 , Lachnoclostridium (Zhao et al, 2017b), Lachnospiraceae UCG-006 (Kang et al, 2019), and Romboutsia (Zhao et al, 2018) were positively correlated with obesity. Bifidobacterium, a beneficial microbial species, producing lactic acid and acetic acid, can reduce intestinal pH and inhibit the growth of various detrimental bacteria to maintain intestinal health (Wang R. et al, 2018).…”

The Effects of Gelatinized Wheat Starch and High Salt Diet on Gut Microbiota and Metabolic Disorder

“…The Muribaculum genus, previously classified as S24-7, is known to decrease in mice on high-fat diet and is associated with the regulation of body weight [25,26]. Moreover, Romboutsia, which is an obesity-related phylotype, is positively associated with lipid profile and lipogenesis in the liver [27]. In this study, WD showed a significantly reduced proportion of Muribaculum and increased proportion of Romboutsia, which may have led to weight gain.…”

Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation

“…(41) Ruminococcaceae UCG-008, Clostridium sensu stricto 1, and Romboutsia, which were also enriched in lean NAFLD, are reported to be strongly correlated with hepatic triglycerides. (42) At a genetic level, we demonstrated that although there was no significant difference in the proportions of patients with PNPLA3 rs738409 GG genotype, a significantly greater proportion of patients with lean NAFLD carried the TM6SF2 rs58542926 (T) allele than patients with nonlean NAFLD. Interestingly, TM6SF2 has been implicated in cholesterol synthesis.…”

“…Use of plant sterol esters to reduce cholesterol in hamsters likewise reduced Erysipelotrichaceae abundance . Ruminococcaceae UCG‐008, Clostridium sensu stricto 1, and Romboutsia , which were also enriched in lean NAFLD, are reported to be strongly correlated with hepatic triglycerides …”