Effect of Liraglutide on Microbiome in Obesity

Summary

The purpose of the trial is to assess whether the beneficial effect of liraglutide on weight is mediated by changes in the composition of the intestinal Microbiome. The main mechanisms of action of liraglutide were traced to a reduction in the secretion of glucagon and slowing gastric emptying resulting in decreased appetite and body weight. It also seems that liraglutide is capable of increasing the satiety signals thanks to a dual mechanism of stimulation and inhibition induced by medication. Pomc neurons (opiomelacortin) present in hypothalamic arcuate nuclei, stimulated by liraglutide, glucagon-like peptide- 1 (GLP-1) receptor expressed by inhibiting intensely appetite. At the same time through the GABAergic neuronal activity is inhibited neuropeptide Y(NPY) deputies to the production of orexins that are powerful promoters of appetite. Alterations in the composition of the human gut microbiome occur in metabolic disorders such as obesity, diabetes. Liraglutide has been reported to switch microbiome composition towards lean-related bacterial phylotypes in animal studies. This leads to hypothesize that the switch of microbiome by liraglutide may be one of the mechanisms through which liraglutide may exert its effect. In particular the investigators hypothesize that liraglutide could restore a healthy microbiome or at least improve the microbiome composition through slowing gastrointestinal motility. Moreover, the liraglutide-related change of microbiome could be an additional mechanism that contribute to the beneficial metabolic effect of liraglutide. To test this hypothesis the investigators will investigate if there will be any change of gut microbiome assessed as Firmicutes-to-Bacteroidetes ratio after liraglutide treatment. In order to understand if the change of gut microbiome after liraglutide treatment occurs as an association or contributes to the effect of liraglutide ,the investigators will correlate the Firmicutes-to-Bacteroidetes ratios with the changes of Body Mass Index, Body Composition, appetite parameters, chronic inflammation parameters, lipid profile and insulin resistance. All the subjects will follow the same diet in order to avoid any bias.

Timeline

Start

2019-01-09

Primary completion

2020-01-09

Completion

2020-04-30

Publications

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• Background Dinan TG, Cryan JF. Mood by microbe: towards clinical translation. Genome Med. 2016 Apr 6;8(1):36. doi: 10.1186/s13073-016-0292-1.
• Background Nakatani Y, Maeda M, Matsumura M, Shimizu R, Banba N, Aso Y, Yasu T, Harasawa H. Effect of GLP-1 receptor agonist on gastrointestinal tract motility and residue rates as evaluated by capsule endoscopy. Diabetes Metab. 2017 Oct;43(5):430-437. doi: 10.1016/j.diabet.2017.05.009. Epub 2017 Jun 23.
• Background Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23. doi: 10.1073/pnas.0407076101. Epub 2004 Oct 25.

Drugs

Indications