ArticleScientific reports2020
Metformin enhances protection in guinea pigs chronically infected with Mycobacterium tuberculosis.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Assessment of tuberculosis drug efficacy using preclinical animal models and in vitro predictive techniques.npj antimicrobials and resistance · 2024Article
- Establishment of CD1b-restricted immunity to lipid antigens in the pulmonary response toInfection and immunity · 2024Article
- Clinical features, immunologic parameter and treatment outcome of Chinese tuberculosis patients with or without DM.Frontiers in medicine · 2024Article
- Metformin improvesFrontiers in immunology · 2024Article
- Recent Advances in Host-Directed Therapies for Tuberculosis and Malaria.Frontiers in cellular and infection microbiology · 2022Review
- Impact of Diabetes Mellitus on the Immunity of Tuberculosis Patients: A Retrospective, Cross-Sectional Study.Risk management and healthcare policy · 2022Article
- Modulating macrophage function to reinforce host innate resistance againstFrontiers in immunology · 2022Review
- Progressive Host-Directed Strategies to Potentiate BCG Vaccination Against Tuberculosis.Frontiers in immunology · 2022Review
- Anti-diabetics and antimicrobials: Harmony of mutual interplay.World journal of diabetes · 2021Review
- Article
- Targeting Molecular Inflammatory Pathways in Granuloma as Host-Directed Therapies for Tuberculosis.Frontiers in immunology · 2021Review
- Lactate Metabolism and Signaling in Tuberculosis and Cancer: A Comparative Review.Frontiers in cellular and infection microbiology · 2021Review
- Understanding the Reciprocal Interplay Between Antibiotics and Host Immune System: How Can We Improve the Anti-Mycobacterial Activity of Current Drugs to Better Control Tuberculosis?Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Tuberculosis (TB) is a chronic inflammatory disease that is often associated with alterations in systemic and cellular metabolism that resolves following successful antimicrobial drug treatment. We hypothesized that altered systemic glucose metabolism as a consequence of Mycobacterium tuberculosis (Mtb) infection, contributes to TB pathogenesis, and when normalized with anti-glycemic drugs would improve clinical outcomes. To test this hypothesis, guinea pigs were treated daily with the anti-diabetic drug metformin starting 4 weeks prior or concurrent with aerosol exposure to the H37Rv strain of Mtb. In the chronic stages of infection, Mtb infected metformin-treated animals had restored systemic insulin sensitivity but remained glucose intolerant as determined by oral glucose tolerance testing. Despite persistent glucose intolerance, metformin-treated guinea pigs had a 2.8-fold reduction in lung lesion burden and a 0.7 log decrease in CFUs. An alternative hypothesis that metformin treatment improved clinical disease by having a direct effect on immune cell energy metabolism was tested using extracellular flux analysis and flow cytometry. The proinflammatory immune response to Mtb infection in untreated guinea pigs was associated with a marked increase in energy metabolism (glycolysis and mitochondrial respiration) of peripheral blood mononuclear cells (PBMCs), which was normalized in metformin-treated guinea pigs. Moreover, both CD4
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