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Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota.

ABSTRACT: Background:People with HIV (PWH) taking antiretroviral therapy (ART) may experience weight gain, dyslipidemia, increased risk of non-AIDS comorbidities, and long-term alteration of the gut microbiota. Both low CD4/CD8 ratio and chronic inflammation have been associated with changes in the gut microbiota of PWH. The antidiabetic drug metformin has been shown to improve gut microbiota composition while decreasing weight and inflammation in diabetes and polycystic ovary syndrome. Nevertheless, it remains unknown whether metformin may benefit PWH receiving ART, especially those with a low CD4/CD8 ratio. Methods:In the Lilac pilot trial, we recruited 23 nondiabetic PWH receiving ART for more than 2 years with a low CD4/CD8 ratio (<0.7). Blood and stool samples were collected during study visits at baseline, after a 12-week metformin treatment, and 12 weeks after discontinuation. Microbiota composition was analyzed by 16S rDNA gene sequencing, and markers of inflammation were assessed in plasma. Results:Metformin decreased weight in PWH, and weight loss was inversely correlated with plasma levels of the satiety factor GDF-15. Furthermore, metformin changed the gut microbiota composition by increasing the abundance of anti-inflammatory bacteria such as butyrate-producing species and the protective Akkermansia muciniphila. Conclusions:Our study provides the first evidence that a 12-week metformin treatment decreased weight and favored anti-inflammatory bacteria abundance in the microbiota of nondiabetic ART-treated PWH. Larger randomized placebo-controlled clinical trials with longer metformin treatment will be needed to further investigate the role of metformin in reducing inflammation and the risk of non-AIDS comorbidities in ART-treated PWH.

SUBMITTER: Isnard S

PROVIDER: S-EPMC7489545 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota.

Isnard Stéphane S Lin John J Fombuena Brandon B Ouyang Jing J Varin Thibault V TV Richard Corentin C Marette André A Ramendra Rayoun R Planas Delphine D Raymond Marchand Laurence L Messaoudene Meriem M Van der Ley Claude P CP Kema Ido P IP Sohail Ahmed Darakhshan D Zhang Yonglong Y Finkelman Malcolm M Routy Bertrand B Angel Jonathan J Ancuta Petronela P Routy Jean-Pierre JP

Open forum infectious diseases 20200911 9

<h4>Background</h4>People with HIV (PWH) taking antiretroviral therapy (ART) may experience weight gain, dyslipidemia, increased risk of non-AIDS comorbidities, and long-term alteration of the gut microbiota. Both low CD4/CD8 ratio and chronic inflammation have been associated with changes in the gut microbiota of PWH. The antidiabetic drug metformin has been shown to improve gut microbiota composition while decreasing weight and inflammation in diabetes and polycystic ovary syndrome. Neverthele ...[more]

PMID: 32964062

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Project description:BackgroundObesity is the cause of cardiovascular diseases and other diseases, leading to increased medical costs, and causing a great burden to individuals, families and society. The prevalence of obesity is increasing and has become a global health problem. There is growing evidence that gut microbiota plays an important role in obesity. In this article, we revealed the differences in the gut microbiota between 21 people with obesity and 21 control subjects, and predicted the functional potential changes by 16S rRNA sequencing of the fecal bacteria of the subjects.MethodsThe raw sequencing data of 21 healthy Beijing volunteers was downloaded from Microbial Genome Database System. Microbial 16S rRNA genes of 21 adults with obesity were sequenced on an Illumina MiSeq instrument and analyzed by using bioinformatics and statistical methods.ResultsThe diversity of gut microbiota in people with obesity decreased significantly. There were significant differences in gut microbiota between the Obesity and Control group at different levels. At the phylum level, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria are significantly different between the Obesity and Control group. In people with obesity, the ratio of Firmicutes/Bacteroidetes decreased significantly. At the genus level, there were significant differences among the 16 major genera, of which four genera Prevotella, Megamonas, Fusobacterium and Blautia increased significantly in people with obesity, while the remaining 12 genera, Faecalibacterium, Lachnospiracea_incertae_sedis, Gemmiger and Clostridium XlVa, etc. decreased significantly. At the species level, nine species including Bacteroides uniformis and Prevotella copri had significant differences. Compared with the control group, subjects with obesity were abnormalities in 57 pathways, mainly in Carbohydrate metabolism and Lipid metabolism.ConclusionsOverall, our study revealed differences in the gut microbiota between people with obesity and control subjects, providing novel target for the treatment of individuals with obesity.

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Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota.

Publications

Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota.

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