Publikácie

@article{Skladany2024677,

title = {3PM-guided innovation in treatments of severe alcohol-associated hepatitis utilizing fecal microbiota transplantation},

author = {Lubomir Skladany and Natalia Kubanek and Svetlana Adamcova Selcanova and Daniela Zilincanova and Daniel Havaj and Karolina Sulejova and Katarina Soltys and Lucia Messingerova and Michal Lichvar and Lukas Laffers and Michal Zilincan and Eva Honsova and Peter Liptak and Peter Banovcin and Jan Bures and Tomas Koller and Olga Golubnitschaja and Juan-Pablo Arab},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85208063179&doi=10.1007%2fs13167-024-00381-5&partnerID=40&md5=46239bf6a6eff5ad80a7a21f5df23405},

doi = {10.1007/s13167-024-00381-5},

issn = {18785077},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {EPMA Journal},

volume = {15},

number = {4},

pages = {677 – 692},

publisher = {Springer Science and Business Media Deutschland GmbH},

abstract = {Rationale: Severe alcohol-associated hepatitis (SAH) is the most critical, acute, inflammatory phenotype within the alcohol-associated liver disease (ALD) spectrum, characterized by high 30- and 90-day mortality. Since several decades, corticosteroids (CS) are the only approved pharmacotherapy offering highly limited survival benefits. Contextually, there is an evident demand for 3PM innovation in the area meeting patients’ needs and improving individual outcomes. Fecal microbiota transplantation (FMT) has emerged as one of the new potential therapeutic options. In this study, we aimed to address the crucial 3PM domains in order to assess (i) the impact of FMT on mortality in SAH patients beyond CS, (ii) to identify factors associated with the outcome to be improved (iii) the prediction of futility, (iv) prevention of suboptimal individual outcomes linked to increased mortality, and (v) personalized allocation of therapy. Methods: We conducted a prospective study (NCT04758806) in adult patients with SAH who were non-responders (NR) to or non-eligible (NE) for CS between January 2018 and August 2022. The intervention consisted of five 100 ml of FMT, prepared from 30 g stool from an unrelated healthy donor and frozen at − 80 °C, administered daily to the upper gastrointestinal (GI) tract. We evaluated the impact of FMT on 30- and 90-day mortality which we compared to the control group selected by the propensity score matching and treated by the standard of care; the control group was derived from the RH7 registry of patients hospitalized at the liver unit (NCT04767945). We have also scrutinized the FMT outcome against established and potential prognostic factors for SAH — such as the model for end-stage liver disease (MELD), Maddrey Discriminant Function (MDF), acute-on-chronic liver failure (ACLF), Liver Frailty Index (LFI), hepatic venous-portal pressure gradient (HVPG) and Alcoholic Hepatitis Histologic Score (AHHS) — to see if the 3PM method assigns them a new dimension in predicting response to therapy, prevention of suboptimal individual outcomes, and personalized patient management. Results: We enrolled 44 patients with SAH (NR or NE) on an intention-to-treat basis; we analyzed 33 patients per protocol for associated factors (after an additional 11 being excluded for receiving less than 5 doses of FMT), and 31 patients by propensity score matching for corresponding individual outcomes, respectively. The mean age was 49.6 years, 11 patients (33.3%) were females. The median MELD score was 29, and ACLF of any degree had 27 patients (81.8%). FMT improved 30-day mortality (p = 0.0204) and non-significantly improved 90-day mortality (p = 0.4386). Univariate analysis identified MELD ≥ 30, MDF ≥ 90, and ACLF grade > 1 as significant predictors of 30-day mortality, (p = 0.031; p = 0.014; p = 0.034). Survival was not associated with baseline LFI, HVPG, or AHHS. Conclusions and recommendations in the framework of 3PM: In the most difficult-to-treat sub-cohort of patients with SAH (i.e., NR/NE), FMT improved 30-day mortality. Factors associated with benefit included MELD ≤ 30, MDF ≤ 90, and ACLF < 2. These results support the potential of gut microbiome as a therapeutic target in the context of 3PM research and vice versa — to use 3PM methodology as the expedient unifying template for microbiome research. The results allow for immediate impact on the innovative concepts of (i) personalized phenotyping and stratification of the disease for the clinical research and practice, (ii) multilevel predictive diagnosis related to personalized/precise treatment allocation including evidence-based (ii) prevention of futile and sub-optimally effective therapy, as well as (iii) targeted prevention of poor individual outcomes in patients with SAH. Moreover, our results add to the existing evidence with the potential to generate new research along the SAH’s pathogenetic pathways such as diverse individual susceptibility to alcohol toxicity, host-specific mitochondrial function and systemic inflammation, and the role of gut dysbiosis thereof. © The Author(s) 2024.},

note = {All Open Access, Hybrid Gold Open Access},

keywords = {Gut microbiome},

pubstate = {published},

tppubtype = {article}

}

@article{Pös2023,

title = {Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer},

author = {O. Pös and J. Styk and G. Buglyó and M. Zeman and L. Lukyova and K. Bernatova and E. Hrckova Turnova and T. Rendek and Á. Csók and V. Repiska and B. Nagy and T. Szemes},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85164844125&doi=10.3390%2fijms241310520&partnerID=40&md5=7a3be1fd203bc9e0cf04f84a8bbfe4de},

doi = {10.3390/ijms241310520},

issn = {16616596},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {International Journal of Molecular Sciences},

volume = {24},

number = {13},

publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},

abstract = {Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile. © 2023 by the authors.},

keywords = {Gut microbiome, Oncology},

pubstate = {published},

tppubtype = {article}

}

@article{Gromova2023,

title = {The effect of plasma-activated water in a mouse model of inflammatory bowel disease},

author = {B. Gromova and B. Konecna and M. Suchonova and S. Pasztor and P. Celec and L. Tothova and M. Lichvar and J. Budis and J. Radvanszky and D. Rusnakova and T. Szemes and Z. Machala and R. Gardlik},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85160071712&doi=10.1002%2fppap.202300053&partnerID=40&md5=bd251feb6cc3883a722e4cee94b96851},

doi = {10.1002/ppap.202300053},

issn = {16128850},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Plasma Processes and Polymers},

volume = {20},

number = {9},

publisher = {John Wiley and Sons Inc},

abstract = {Inflammatory bowel disease (IBD) is a group of disorders with complex pathogenesis, including oxidative stress and microbial dysbiosis. The aim of this study was to analyze the effect of intracolonic administration of plasma-activated water (PAW) on the oxidative status and gut microbiota diversity in the colon of healthy mice and mice with IBD. Interestingly, PAW increased oxidative stress markers in the colon tissue, and this effect was more pronounced in IBD mice. Our results show that PAW increases microbial diversity in a healthy gut and decreases it in an inflamed gut. We conclude that the effect of PAW is bidirectional and depends on the underlying condition. Our findings do not support the proposed therapeutic potential of PAW in IBD. © 2023 Wiley-VCH GmbH.},

keywords = {Gut microbiome},

pubstate = {published},

tppubtype = {article}

}

@article{Bielik2020,

title = {Gut microbiota diversity in lean athletes is associated with positive energy balance},

author = {V Bielik and I Hric and V BalᎠand A Penesová and S Vávrová and J Grones and B Bokor and J Budiš and M Bohmer and G Minárik and D Augustovičová and K Šoltys},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091307627&doi=10.1159%2f000509833&partnerID=40&md5=4461653fb07e53dc12411cda7d4cb566},

doi = {10.1159/000509833},

issn = {02506807},

year  = {2020},

date = {2020-01-01},

journal = {Annals of Nutrition and Metabolism},

publisher = {S. Karger AG},

abstract = {Introduction: In contrast to obesity, little is known about the human lean phenotype associated with gut microbiota composition. Objective: We aimed to investigate whether the bacterial composition of lean athletes with a positive energy balance differs from the equal-calorie food group. Methods: Twenty-four male participants were included in this cross-sectional study: lean athletes with a positive energy balance (LA, n 12) and control group athletes (CTRLs, n 12). Nutritional data, resting and total energy expenditure, and body composition were determined. DNA was extracted from stool samples and subjected to 16S rRNA gene analysis. Results: We found 7 differentially abundant bacterial taxa between the LA and CTRL groups. Of those, 5 were significantly less abundant and 2 were enriched in the LA group. The following categories significantly associated with the community structure were identified: body fat parameters, BMI, energy intake and expenditure, oxygen consumption, and respiratory exchange ratio. Conclusions: Although we are far from a detailed interpretation of lean human body maintenance, the primary findings of our study suggest that gut microbial composition may be a factor influencing the regulation of weight gain in lean athletes with a positive energy balance. © 2020 Cambridge University Press. All rights reserved.},

keywords = {Bacteria, Gut microbiome, Metagenomics},

pubstate = {published},

tppubtype = {article}

}