Metformin Therapy Changes Gut Microbiota Alpha-Diversity in COVID-19 Patients with Type 2 Diabetes: The Role of SARS-CoV-2 Variants and Antibiotic Treatment

Petakh, Pavlo; Kamyshna, Iryna; Oksenych, Valentyn; Kainov, Denis E.; Kamyshnyі, Аleksandr

doi:10.3390/ph16060904

Cited by 11 publications

(6 citation statements)

References 52 publications

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“…Although we did not observe changes in the F/B ratio between patients taking and not taking metformin, several studies have reported that obese and diabetic patients exhibit a higher F/B ratio compared to healthy subjects [30,31]. Patients taking metformin showed higher indices of alpha diversity, aligning with findings from previous studies [32].…”

Section: Discussionsupporting

confidence: 91%

Metformin Alters mRNA Expression of FOXP3, RORC, and TBX21 and Modulates Gut Microbiota in COVID-19 Patients with Type 2 Diabetes

Petakh,

Kamyshna,

Oksenych

et al. 2024

Viruses

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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 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.

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Section: Discussionsupporting

confidence: 91%

Metformin Alters mRNA Expression of FOXP3, RORC, and TBX21 and Modulates Gut Microbiota in COVID-19 Patients with Type 2 Diabetes

Petakh,

Kamyshna,

Oksenych

et al. 2024

Viruses

Self Cite

View full text Add to dashboard Cite

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“…The gut microbiota diversity in COVID-19 patients and Type 2 diabetes patients may be influenced by antibiotic use and T2D. Metformin treatment may modulate gut microbiota and reduce oxidative stress, highlighting the importance of gut microbiota in T2D management [24] . A study confirms that SARS-CoV-2 infection is linked to antimicrobial resistance in the gut microbiota.…”

Section: Discussionmentioning

confidence: 99%

The influence of coronaviruses on the human gut microflora

Hejran,

Sarwari,

Monib

et al. 2024

Int. J. Adv. Biochem. Res.

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The influence of coronaviruses on the human gut microflora is a topic of emerging interest within the scientific community. Coronaviruses, particularly those like SARS-CoV-2, which causes COVID-19, are primarily known for respiratory symptoms but have broader impacts on human health. Recent research suggests that coronaviruses can affect the gut microflora, the diverse community of microorganisms inhabiting the gastrointestinal tract, which plays a crucial role in human health and disease. Studies indicate that coronaviruses may disrupt the gut microflora directly or indirectly. Direct effects could occur through viral invasion of intestinal cells expressing the ACE2 receptor, which is the cellular entry point for coronaviruses. Indirect effects may arise due to systemic inflammation triggered by the viral infection, affecting gut microbial composition and function. Dysbiosis, an imbalance in gut microbial communities, has been observed in COVID-19 patients, indicating potential coronavirusmediated alterations. Understanding these interactions is vital because the gut microflora influences immune responses, nutrient metabolism, and overall well-being. Altered microbial profiles due to coronavirus infections might contribute to the prolonged gastrointestinal symptoms reported in COVID-19 patients. Moreover, changes in gut microflora composition could impact the efficacy of therapies and vaccines, given the role of the microflora in modulating immune system function. Future research should explore the mechanisms underlying coronavirus-mediated alterations in gut microflora and their implications for health outcomes. This includes investigating how viral infections influence specific microbial species and their metabolic activities. Longitudinal studies are needed to assess whether these changes persist beyond the acute phase of infection and how they correlate with clinical outcomes. In summary, coronaviruses can exert significant influences on the human gut microflora, potentially disrupting microbial communities and functions essential for health. This understanding could inform therapeutic strategies targeting gut microflora to improve outcomes in coronavirusinfected individuals and enhance our broader understanding of host-microflora interactions in infectious diseases.

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“…On the other hand, dysbiosis in the intestinal microbiota has been described as contributing to the appearance and progression of many viral diseases, including COVID-19 and its subsequent manifestations (long COVID) [ 114 ]. MET has been shown to modulate the intestinal microbiota in patients with COVID-19, increasing the alpha diversity of bacteria, which contributes to the modulation of the immune response and reduces the appearance of long COVID cases [ 14 , 115 , 116 ].…”

Section: Retrospective Studies and Clinical Trials That Have Evaluate...mentioning

confidence: 99%

A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin

De Jesús-González,

del Ángel,

Palacios-Rápalo

et al. 2024

Microorganisms

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Metformin (MET) and atorvastatin (ATO) are promising treatments for COVID-19. This review explores the potential of MET and ATO, commonly prescribed for diabetes and dyslipidemia, respectively, as versatile medicines against SARS-CoV-2. Due to their immunomodulatory and antiviral capabilities, as well as their cost-effectiveness and ubiquitous availability, they are highly suitable options for treating the virus. MET’s effect extends beyond managing blood sugar, impacting pathways that can potentially decrease the severity and fatality rates linked with COVID-19. It can partially block mitochondrial complex I and stimulate AMPK, which indicates that it can be used more widely in managing viral infections. ATO, however, impacts cholesterol metabolism, a crucial element of the viral replicative cycle, and demonstrates anti-inflammatory characteristics that could modulate intense immune reactions in individuals with COVID-19. Retrospective investigations and clinical trials show decreased hospitalizations, severity, and mortality rates in patients receiving these medications. Nevertheless, the journey from observing something to applying it in a therapeutic setting is intricate, and the inherent diversity of the data necessitates carefully executed, forward-looking clinical trials. This review highlights the requirement for efficacious, easily obtainable, and secure COVID-19 therapeutics and identifies MET and ATO as promising treatments in this worldwide health emergency.

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Metformin Therapy Changes Gut Microbiota Alpha-Diversity in COVID-19 Patients with Type 2 Diabetes: The Role of SARS-CoV-2 Variants and Antibiotic Treatment

Cited by 11 publications

References 52 publications

Metformin Alters mRNA Expression of FOXP3, RORC, and TBX21 and Modulates Gut Microbiota in COVID-19 Patients with Type 2 Diabetes

Metformin Alters mRNA Expression of FOXP3, RORC, and TBX21 and Modulates Gut Microbiota in COVID-19 Patients with Type 2 Diabetes

The influence of coronaviruses on the human gut microflora

A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin

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