Metformin Alters mRNA Expression of FOXP3, RORC, and TBX21 and Modulates Gut Microbiota in COVID-19 Patients with Type 2 Diabetes
Pavlo Petakh, Iryna Kamyshna, Valentyn Oksenych, Oleksandr Kamyshnyi
Viruses, doi:10.3390/v16020281
COVID-19 remains a significant global concern, particularly for individuals with type 2 diabetes who face an elevated risk of hospitalization and mortality. Metformin, a primary treatment for type 2 diabetes, demonstrates promising pleiotropic properties that may substantially mitigate disease severity and expedite recovery. Our study of the gut microbiota and the mRNA expression of pro-inflammatory and anti-inflammatory T-lymphocyte subpopulations showed that metformin increases bacterial diversity while modulating gene expression related to T-lymphocytes. This study found that people who did not take metformin had a downregulated expression of FOXP3 by 6.62fold, upregulated expression of RORC by 29.0-fold, and upregulated TBX21 by 1.78-fold, compared to the control group. On the other hand, metformin patients showed a 1.96-fold upregulation in FOXP3 expression compared to the control group, along with a 1.84-fold downregulation in RORC expression and an 11.4-fold downregulation in TBX21 expression. Additionally, we found a correlation with gut microbiota (F/B ratio and alpha-diversity index) and pro-inflammatory biomarkers. This novel observation of metformin's impact on T-cells and gut microbiota opens new horizons for further exploration through clinical trials to validate and confirm our data. The potential of metformin to modulate immune responses and enhance gut microbiota diversity suggests a promising avenue for therapeutic interventions in individuals with type 2 diabetes facing an increased risk of severe outcomes from COVID-19.
Author Contributions: Conceptualization, O.K.; methodology, O.K.; software, O.K.; validation, O.K. and P.P.; formal analysis, P.P.; investigation, O.K.; data curation, O.K.; writing-original draft preparation, P.P.; writing-review and editing, V.O.; visualization, P.P.; supervision, O.K.; project administration, I.K. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding.
Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of I. Horbachevsky Ternopil National Medical University (protocol code 74 on 1 September 2023). Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Conflicts of Interest: The authors declare no conflicts of interest.
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'abstract': '<jats:p>COVID-19 remains a significant global concern, particularly for individuals with type '
'2 diabetes who face an elevated risk of hospitalization and mortality. Metformin, a primary '
'treatment for type 2 diabetes, demonstrates promising pleiotropic properties that may '
'substantially mitigate disease severity and expedite recovery. Our study of the gut '
'microbiota and the mRNA expression of pro-inflammatory and anti-inflammatory T-lymphocyte '
'subpopulations showed that metformin increases bacterial diversity while modulating gene '
'expression related to T-lymphocytes. This study found that people who did not take metformin '
'had a downregulated expression of FOXP3 by 6.62-fold, upregulated expression of RORC by '
'29.0-fold, and upregulated TBX21 by 1.78-fold, compared to the control group. On the other '
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'downregulation in TBX21 expression. Additionally, we found a correlation with gut microbiota '
'(F/B ratio and alpha-diversity index) and pro-inflammatory biomarkers. This novel observation '
'of metformin’s impact on T-cells and gut microbiota opens new horizons for further '
'exploration through clinical trials to validate and confirm our data. The potential of '
'metformin to modulate immune responses and enhance gut microbiota diversity suggests a '
'promising avenue for therapeutic interventions in individuals with type 2 diabetes facing an '
'increased risk of severe outcomes from COVID-19.</jats:p>',
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'first-page': '100142',
'article-title': 'Effect of early treatment with metformin on risk of emergency care and '
'hospitalization among patients with COVID-19: The TOGETHER randomized '
'platform clinical trial',
'volume': '6',
'author': 'Reis',
'year': '2022',
'journal-title': 'Lancet Reg. Health Am.'}],
'container-title': 'Viruses',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.mdpi.com/1999-4915/16/2/281/pdf',
'content-type': 'unspecified',
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'deposited': { 'date-parts': [[2024, 2, 12]],
'date-time': '2024-02-12T10:10:05Z',
'timestamp': 1707732605000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.mdpi.com/1999-4915/16/2/281'}},
'subtitle': [],
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'issued': {'date-parts': [[2024, 2, 11]]},
'references-count': 37,
'journal-issue': {'issue': '2', 'published-online': {'date-parts': [[2024, 2]]}},
'alternative-id': ['v16020281'],
'URL': 'http://dx.doi.org/10.3390/v16020281',
'relation': {},
'ISSN': ['1999-4915'],
'subject': ['Virology', 'Infectious Diseases'],
'container-title-short': 'Viruses',
'published': {'date-parts': [[2024, 2, 11]]}}
