Petakh P. SARS-CoV-2-induced changes in gut microbiota and lymphocyte immunometabolism in patients with type 2 diabetes

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0823U101701

Applicant for

Specialization

  • 222 - Медицина

16-01-2024

Specialized Academic Board

ДФ58.601.105 ID3619

Ternopil National Medical University named after I. Gorbachevsky of the Ministry of Health of Ukraine

Essay

The dissertation is dedicated to the study of changes in the gut microbiota and the functional state of lymphocytes in patients with COVID-19 and type 2 diabetes (T2D). The dissertation is to identify distinctive changes in the gut microbiota of patients with both COVID-19 and T2D undergoing metformin or antibiotic therapy, revealing alterations in the abundance of individual genera as well as shifts in alpha diversity indices. The study established novel correlations between the abundances of individual microbial genera and alpha diversity indices with inflammatory biomarkers like CRP and NLR. Additionally, the research demonstrated that while the presence of T2D in COVID-19 patients didn't significantly impact the alpha diversity of the gut microbiota, patients with T2D and COVID-19 who underwent antibiotic therapy and metformin exhibited noteworthy differences in alpha diversity indices compared to those without antibiotic therapy. Moreover, the research highlighted the higher F/B ratio in patients with both COVID-19 and T2D in contrast to patients with only COVID-19 and without T2D, along with the correlations between this ratio and CRP levels. Furthermore, the investigation explored changes in the transcriptional activity of PRKAA1, SLC2A1, and MTOR genes in patients with both COVID-19 and T2D. It was observed that antibacterial therapy did not influence the gene expression of these genes. Patients with COVID-19 and T2D receiving insulin therapy demonstrated decreased PRKAA1 gene expression and increased SLC2A1 and MTOR gene expression. The administration of metformin resulted in increased PRKAA1 gene expression but decreased expression levels of SLC2A1 and MTOR genes. Correlations were established between the expression levels of these genes and inflammatory biomarkers (NLR, CRP, and procalcitonin), suggesting a potential influence of these genes on the course of COVID-19 in patients with T2D.

Research papers

1. Petakh P, Griga V, Mohammed IB, Loshak K, Poliak I, Kamyshnyiy A. Effects of Metformin, Insulin on Hematological Parameters of COVID-19 Patients with Type 2 Diabetes. Medical archives (Sarajevo, Bosnia and Herzegovina). 2022;76(5):329-32. DOI: 10.5455/medarh.2022.76.329-332

2. Petakh P, Loshak K, Kamyshnyi A. Hematological features of patients with type 2 diabetes depending on the variant of SARS-COV-2. Fiziolohichnyĭ Zhurnal. 2023;69(1):35-42. DOI: 10.15407/fz69.01.035

3. Petakh P, Kobyliak N, Kamyshnyi A. Gut microbiota in patients with COVID-19 and type 2 diabetes: A culture-based method. Front Cell Infect Microbiol. 2023 Feb 9;13:1142578. DOI: 10.3389/fcimb.2023.1142578

4. Petakh P, Kamyshna I, Oksenych V, Kainov D, Kamyshnyi A. 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. Pharmaceuticals (Basel). 2023 Jun 20;16(6):904 DOI: 10.3390/ph16060904

5. Petakh P, Oksenych V, Kamyshnyi A. The F/B ratio as a biomarker for inflammation in COVID-19 and T2D: Impact of metformin. Biomedicine & Pharmacotherapy. 2023;163:114892. DOI: 10.1016/j.biopha.2023.114892

6. Petakh P, Kamyshna I, Kamyshnyi A. Effects of metformin on the gut microbiota: A systematic review. Mol Metab. 2023 Sep 9;77:101805. DOI: 10.1016/j.molmet.2023.101805

7. Petakh P, Kamyshna I, Kamyshnyi A. Gene expression of protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), solute carrier family 2 member 1 (SLC2A1) and mechanistic target of rapamycin (MTOR) in metformin-treated type 2 diabetes patients with COVID-19: impact on inflammation markers. Inflammopharmacology. 2023:1-7. DOI: 10.1007/s10787-023-01341-7

Petakh P, Kamyshna I, Nykyforuk A, Yao R, Imbery J, Oksenych V, Korda M, Kamyshnyi A. Immunoregulatory Intestinal Microbiota and COVID-19 in Patients with Type Two Diabetes: A Double-Edged Sword. Viruses. 2022;14:477. DOI: 10.3390/v14030477

Petakh P, Kamyshna I, Kamyshnyi A. Unveiling the Potential Pleiotropic Effects of Metformin in Treating COVID-19: A Comprehensive Review. Front Mol Biosci. 2023;10:1260633. DOI: 10.3389/fmolb.2023.1260633

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