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Zhaivoronok M, Dynnyk O, Livkutnyk O, Yerokhovych V, Yuzvenko V, Serednia I, Melnychenko Y, Kobyliak N. Inter- and Intraobserver variability of attenuation coefficient measurement in innovative ultrasound diagnosis of metabolic dysfunction-associated steatotic liver disease: a cross-sectional study. Front Med (Lausanne) 2025; 12:1457960. [PMID: 40182858 PMCID: PMC11965890 DOI: 10.3389/fmed.2025.1457960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 02/28/2025] [Indexed: 04/05/2025] Open
Abstract
Introduction Evaluation of the ultrasound attenuation coefficient is widely used in the diagnosis of steatotic liver disease (SLD). US steatometry with real-time attenuation coefficient measurement (ACM) is an imaging tool that can replace and surpass the B-mode and improve the noninvasive diagnosis of SLD. Aim To evaluate the intra- and interobserver variability of ACM for the assessment of SLD. Materials and methods A single-center cross-sectional study was conducted at the Kyiv City Clinical Endocrinology Center. We examined 52 patients (25 men and 27 women) with a mean age of 53.2 ± 4.73 years. B-mode and ACM were performed on a Soneus P7 US system (Ultrasign, Ukraine). Examinations were performed by 2 radiologists with 28 (expert 1) and 17 (expert 2) years of experience and 4 general practitioners (GPs) without US experience (nonexperts 1-4). The training of 4 GPs on mastering the ACM was only 60 min due to US steatophantom. Each doctor performed 5 measurements of the ACM for each patient. The inter- and intraobserver variability of the results was determined by using an intraclass correlation coefficient (ICC) with a 95% confidence interval (95% CI). Results The overall intraobserver variability after 5 days of examination was as follows: for expert 1-0.958 (95% CI 0.938-0.974); for expert 2-0.936 (95% CI 0.905-0.980); nonexpert 1-0.891 (95% CI 0.843-0.929); nonexpert 2-0.915 (95% CI 0.876-0.945); nonexpert 3-0.927 (95% CI 0.893-0.953); nonexpert 4-0.880 (95% CI 0.827-0.927). Interobserver variability at the final timepoint (day 5) was as follows: between experts 1 and 2, 0.942 (95% CI 0.898-0.967); between nonexperts 1-4 overall, 0.871 (95% CI 0.800-0.921); and overall, 0.922 (95% CI 0.883-0.951). Conclusion Real-time US steatometry with ACM measurement is an informative, simple method with excellent intra- and interobserver variability and a reproducible method for population assessment for the early diagnosis and staging of SLD. The simplicity of ACM technology allows general practitioners to master the technique within 60 min. ACM measurements can be effectively employed by general practitioners (GPs) for population screening, enabling timely identification and management of MASLD.
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Affiliation(s)
- Maksym Zhaivoronok
- Department of Nuclear Medicine, Radiation Oncology and Radiation Safety of Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine
| | - Oleh Dynnyk
- “Institute of Elastography” Medical Center LLC, Kyiv, Ukraine
| | | | | | - Violetta Yuzvenko
- Endocrinology Department, Bogomolets National Medical University, Kyiv, Ukraine
- Ukrainian Scientific and Practical Center for Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine, Kyiv, Ukraine
| | - Iryna Serednia
- Endocrinology Department, Bogomolets National Medical University, Kyiv, Ukraine
| | | | - Nazarii Kobyliak
- Endocrinology Department, Bogomolets National Medical University, Kyiv, Ukraine
- Medical Laboratory CSD, Kyiv, Ukraine
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Kazeminasab F, Miraghajani M, Mokhtari K, Karimi B, Rosenkranz SK, Santos HO. The effects of probiotic supplementation and exercise training on liver enzymes and cardiometabolic markers in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomized clinical trials. Nutr Metab (Lond) 2024; 21:59. [PMID: 39090657 PMCID: PMC11293022 DOI: 10.1186/s12986-024-00826-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 07/08/2024] [Indexed: 08/04/2024] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver ailment worldwide, in which nonpharmacological strategies have a considerable role in the treatment. Probiotic supplementation as well as physical exercise can improve cardiometabolic parameters, but further research is needed to determine the effects of combined treatment versus exercise alone in managing NAFLD-associated biomarkers, primarily liver enzymes, lipid markers, and insulin resistance. OBJECTIVES This systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation, combined with exercise versus exercise alone, on liver enzymes and cardiometabolic markers in patients with NAFLD. METHODS A systematic review and meta-analysis of randomized clinical trials was performed by searching PubMed, Scopus, and Web of Science databases up to April 2024. The search was restricted to articles published in the English language and human studies. Random effects models were used to calculate weighted mean differences (WMD). RESULTS Pooled estimates (9 studies, 615 patients, intervention durations ranging from 8 to 48 weeks) revealed that probiotics plus exercise decreased aspartate transaminase (AST) [WMD=-5.64 U/L, p = 0.02], gamma-glutamyl transferase (GGT) [WMD=-7.09 U/L, p = 0.004], low-density lipoprotein (LDL) [WMD=-8.98 mg/dL, p = 0.03], total cholesterol (TC) [WMD=-16.97 mg/dL, p = 0.01], and homeostatic model assessment for insulin resistance (HOMA-IR) [WMD=-0.94, p = 0.005] significantly more than exercise only. However, probiotics plus exercise did not significantly change high-density lipoprotein (HDL) [WMD = 0.07 mg/dL, p = 0.9], fasting insulin [WMD=-1.47 µIU/mL, p = 0.4] or fasting blood glucose (FBG) [WMD=-1.57 mg/dL, p = 0.3] compared with exercise only. While not statistically significant, there were clinically relevant reductions in alanine aminotransferase (ALT) [WMD=-6.78 U/L, p = 0.1], triglycerides (TG) [WMD=-21.84 mg/dL, p = 0.1], and body weight (BW) [WMD=-1.45 kg, p = 0.5] for probiotics plus exercise compared with exercise only. The included studies exhibited significant heterogeneity for AST (I2 = 78.99%, p = 0.001), GGT (I2 = 73.87%, p = 0.004), LDL (I2 = 62.78%, p = 0.02), TC (I2 = 72.41%, p = 0.003), HOMA-IR (I2 = 93.86%, p = 0.001), HDL (I2 = 0.00%, p = 0.9), FBG (I2 = 66.30%, p = 0.01), ALT (I2 = 88.08%, p = 0.001), and TG (I2 = 85.46%, p = 0.001). There was no significant heterogeneity among the included studies for BW (I2 = 0.00%, p = 0.9). CONCLUSION Probiotic supplementation combined with exercise training elicited better results compared to exercise alone on liver enzymes, lipid profile, and insulin resistance in patients with NAFLD. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42023424290.
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Affiliation(s)
- Fatemeh Kazeminasab
- Department of Physical Education and Sport Sciences, Faculty of Humanities, University of Kashan, Kashan, Iran.
| | - Maryam Miraghajani
- Department of Cancer Research Center, Shahid Beheshti of Medical Sciences, Tehran, Iran
| | - Khatereh Mokhtari
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Bahareh Karimi
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Sara K Rosenkranz
- Department of Kinesiology and Nutrition Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA
| | - Heitor O Santos
- School of Medicine, Federal University of Uberlandia (UFU), Para Street, 1720, Umuarama. Block 2H, Uberlandia, Minas Gerais, 38400-902, Brazil.
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Yang Y, Yang L, Wu J, Hu J, Wan M, Bie J, Li J, Pan D, Sun G, Yang C. Optimal probiotic combinations for treating nonalcoholic fatty liver disease: A systematic review and network meta-analysis. Clin Nutr 2024; 43:1224-1239. [PMID: 38643738 DOI: 10.1016/j.clnu.2024.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 03/20/2024] [Accepted: 04/01/2024] [Indexed: 04/23/2024]
Abstract
BACKGROUND Probiotic administration is a promising therapy for improving conditions in NAFLD patients. This network meta-analysis aimed to compare and estimate the relative effects of probiotic interventions and identify the optimal probiotic species for the treatment of NAFLD (Nonalcoholic fatty liver disease) patients. METHODS The PubMed, Web of Science, Embase, and Cochrane databases were searched from inception to 29 January 2024 to identify RCTs that were published in English. The GRADE framework was used to assess the quality of evidence contributing to each network estimate. RESULTS A total of 35 RCTs involving 2212 NAFLD patients were included in the analysis. For primary outcomes, Lactobacillus + Bifidobacterium + Streptococcus exhibited the highest probability of being the finest probiotic combination in terms of enhancing acceptability as well as reducing AST (SMD: -1.95 95% CI: -2.90, -0.99), ALT (SMD = -1.67, 95% CI: -2.48, -0.85), and GGT levels (SMD = -2.17, 95% CI: -3.27, -1.06). In terms of the secondary outcomes, Lactobacillus + Bifidobacterium + Streptococcus was also the best probiotic combination for reducing BMI (SMD = -0.45, 95% CI: -0.86, -0.04), LDL levels (SMD = -0.45, 95% CI: -0.87, -0.02), TC levels (SMD = -1.09, 95% CI: -1.89, -0.29), and TNF-α levels (SMD = -1.73, 95% CI: -2.72, -0.74). CONCLUSION This network meta-analysis revealed that Lactobacillus + Bifidobacterium + Streptococcus may be the most effective probiotic combination for the treatment of liver enzymes, lipid profiles, and inflammation factors. These findings can be used to guide the development of a probiotics-based treatment guideline for NAFLD since there are few direct comparisons between different therapies.
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Affiliation(s)
- Yafang Yang
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Ligang Yang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China
| | - Jiale Wu
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Jing Hu
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Min Wan
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Jindi Bie
- Department of Clinical Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Jiaxin Li
- Department of Clinical Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China
| | - Da Pan
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China
| | - Guiju Sun
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China
| | - Chao Yang
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214000, China.
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Shvets Y, Khranovska N, Senchylo N, Ostapchenko D, Tymoshenko I, Onysenko S, Kobyliak N, Falalyeyeva T. Microbiota substances modulate dendritic cells activity: A critical view. Heliyon 2024; 10:e27125. [PMID: 38444507 PMCID: PMC10912702 DOI: 10.1016/j.heliyon.2024.e27125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 02/23/2024] [Accepted: 02/23/2024] [Indexed: 03/07/2024] Open
Abstract
Contemporary research in the field of microbiota shows that commensal bacteria influence physiological activity of different organs and systems of a human organism, such as brain, lungs, immune and metabolic systems. This influence is realized by various processes. One of them is trough modulation of immune mechanisms. Interactions between microbiota and the human immune system are known to be complex and ambiguous. Dendritic cells (DCs) are unique cells, which initiate the development and polarization of adaptive immune response. These cells also interconnect native and specific immune reactivity. A large set of biochemical signals from microbiota in the form of different microbiota associated molecular patterns (MAMPs) and bacterial metabolites that act locally and distantly in the human organism. As a result, commensal bacteria influence the maturity and activity of dendritic cells and affect the overall immune reactivity of the human organism. It then determines the response to pathogenic microorganisms, inflammation, associated with different pathological conditions and even affects the effectiveness of vaccination.
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Affiliation(s)
- Yuliia Shvets
- Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska Str., Kyiv, Ukraine
| | - Natalia Khranovska
- National Cancer Institute of Ukraine, 33/43 Yuliia Zdanovska Str., Kyiv, Ukraine
| | - Natalia Senchylo
- Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska Str., Kyiv, Ukraine
| | - Danylo Ostapchenko
- Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska Str., Kyiv, Ukraine
| | - Iryna Tymoshenko
- Bogomolets National Medical University, 13 Shevchenka Blvd., Kyiv, Ukraine
| | - Svitlana Onysenko
- Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska Str., Kyiv, Ukraine
| | - Nazarii Kobyliak
- Bogomolets National Medical University, 13 Shevchenka Blvd., Kyiv, Ukraine
- Medical Laboratory CSD, 22b Zhmerynska Str., Kyiv, Ukraine
| | - Tetyana Falalyeyeva
- Taras Shevchenko National University of Kyiv, 64/13 Volodymyrska Str., Kyiv, Ukraine
- Medical Laboratory CSD, 22b Zhmerynska Str., Kyiv, Ukraine
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Savytska M, Kyriienko D, Zaychenko G, Ostapchenko D, Falalyeyeva T, Kobyliak N. Probiotic co-supplementation with absorbent smectite for pancreatic beta-cell function in type 2 diabetes: a secondary-data analysis of a randomized double-blind controlled trials. Front Endocrinol (Lausanne) 2024; 15:1276642. [PMID: 38405158 PMCID: PMC10890794 DOI: 10.3389/fendo.2024.1276642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 01/18/2024] [Indexed: 02/27/2024] Open
Abstract
Introduction There is growing evidence from animal and clinical studies suggesting probiotics can positively affect type 2 diabetes (T2D). In a previous randomized clinical study, we found that administering a live multistrain probiotic and absorbent smectite once a day for eight weeks to patients with T2D could reduce chronic systemic inflammatory state, insulin resistance, waist circumference and improve the glycemic profile. However, there is a lack of evidence supporting the efficacy of probiotic co-supplementation with absorbent smectite on pancreatic β-cell function in T2D. Aim This secondary analysis aimed to assess the effectiveness of an alive multistrain probiotic co-supplementation with absorbent smectite vs placebo on β-cell function in T2D patients. Material and methods We performed a secondary analysis on a previously published randomized controlled trial (NCT04293731, NCT03614039) involving 46 patients with T2D. The main inclusion criteria were the presence of β-cell dysfunction (%B<60%) and insulin therapy alone or combined with oral anti-diabetic drugs. The primary outcome was assessing β-cell function as change C-peptide and %B. Results We observed only a tendency for improving β-cell function (44.22 ± 12.80 vs 55.69 ± 25.75; р=0.094). The effectiveness of the therapy probiotic-smectite group was confirmed by fasting glycemia decreased by 14% (p=0.019), HbA1c - 5% (p=0.007), HOMA-2 - 17% (p=0.003) and increase of insulin sensitivity by 23% (p=0.005). Analysis of the cytokine profile showed that statistical differences after treatment were in the concentration of both pro-inflammatory cytokines: IL-1β (22.83 ± 9.04 vs 19.03 ± 5.57; p=0.045) and TNF-α (31.25 ± 11.32 vs 26.23 ± 10.13; p=0.041). Conclusion Adding a live multistrain probiotic and absorbent smectite supplement slightly improved β-cell function and reduced glycemic-related parameters in patients with T2D. This suggests that adjusting the gut microbiota could be a promising treatment for diabetes and warrants further investigation through more extensive studies.
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Affiliation(s)
- Maryana Savytska
- Normal Physiology Department, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | | | - Ganna Zaychenko
- Pharmacology Department, Bogomolets National Medical University, Kyiv, Ukraine
| | - Danylo Ostapchenko
- Educational-Scientific Center “Institute of Biology and Medicine” Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
| | - Tetyana Falalyeyeva
- Educational-Scientific Center “Institute of Biology and Medicine” Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
- Medical Laboratory CSD, Kyiv, Ukraine
| | - Nazarii Kobyliak
- Medical Laboratory CSD, Kyiv, Ukraine
- Endocrinology Department, Bogomolets National Medical University, Kyiv, Ukraine
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Kaul R, Paul P, Harfouche M, Saliba R, Chaari A. Microbiome-modulating nutraceuticals ameliorate dyslipidemia in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials. Diabetes Metab Res Rev 2024; 40:e3675. [PMID: 37381688 DOI: 10.1002/dmrr.3675] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 03/26/2023] [Accepted: 05/19/2023] [Indexed: 06/30/2023]
Abstract
AIMS Type 2 Diabetes is intrinsically linked to cardiovascular disease (CVD) via diabetic dyslipidemia, both of which remain global health concerns with annually increasing prevalence. Given the established links between gut microbiome dysbiosis and metabolic diseases, its modulation is an attractive target to ameliorate metabolic imbalances in such patients. There is a need to quantitively summarise, analyse, and describe future directions in this field. METHODS We conducted a systematic review, meta-analysis, and meta-regression following searches in major scientific databases for clinical trials investigating the effect of pro/pre/synbiotics on lipid profile published until April 2022. Data were pooled using random-effects meta-analysis and reported as mean differences with 95% confidence intervals (CIs). PROSPERO No. CRD42022348525. RESULTS Data from 47 trial comparisons across 42 studies (n = 2692) revealed that, compared to placebo/control groups, the administration of pro/pre/synbiotics was associated with statistically significant changes in total cholesterol (-9.97 mg/dL [95% CI: -15.08; -4.87], p < 0.0001), low-density lipoprotein (-6.29 mg/dL [95% CI: -9.25; -3.33], p < 0.0001), high-density lipoprotein (+3.21 mg/dL [95% CI: 2.20; 4.22], p < 0.0001), very-low-density lipoprotein (-4.52 mg/dL [95% CI: -6.36; -2.67], p < 0.0001) and triglyceride (-22.93 mg/dL [95% CI: -33.99; -11.87], p < 0.001). These results are influenced by patient characteristics such as age or baseline BMI, and intervention characteristics such as dosage and duration. CONCLUSIONS Our study shows that adjunct supplementation with a subset of pro/pre/synbiotics ameliorates dyslipidemia in diabetic individuals and has the potential to reduce CVD risk. However, widespread inter-study heterogeneity and the presence of several unknown confounders limit their adoption in clinical practice; future trials should be designed with these in mind.
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Affiliation(s)
- Ridhima Kaul
- Medical Education Division, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - Pradipta Paul
- Medical Education Division, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - Manale Harfouche
- Infectious Disease Epidemiology Group, Weill Cornell Medicine - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
- World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - Reya Saliba
- Health Sciences Library, Weill Cornell Medicine - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar
| | - Ali Chaari
- Premedical Division, Weill Cornell Medicine - Qatar, Qatar Foundation - Education City, Doha, Qatar
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Rong L, Ch'ng D, Jia P, Tsoi KKF, Wong SH, Sung JJY. Use of probiotics, prebiotics, and synbiotics in non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2023; 38:1682-1694. [PMID: 37409560 DOI: 10.1111/jgh.16256] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 05/18/2023] [Accepted: 05/29/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND AND AIM Patients with non-alcoholic fatty liver disease (NAFLD) exhibit compositional changes in their gut microbiome, which represents a potential therapeutic target. Probiotics, prebiotics, and synbiotics are microbiome-targeted therapies that have been proposed as treatment for NAFLD. We aim to systematically review the effects of these therapies in liver-related outcomes of NAFLD patients. METHODS We conducted a systematic search in Embase (Ovid), Medline (Ovid), Scopus, Cochrane, and EBSCOhost from inception to August 19, 2022. We included randomized controlled trials (RCTs) that treated NAFLD patients with prebiotics and/or probiotics. We meta-analyzed the outcomes using standardized mean difference (SMD) and assessed study heterogeneity using Cochran's Q test and I2 statistics. Risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool. RESULTS A total of 41 (18 probiotics, 17 synbiotics, and 6 prebiotics) RCTs were included. Pooled data demonstrated that the intervention had significantly improved liver steatosis (measured by ultrasound grading) (SMD: 4.87; 95% confidence interval [CI]: 3.27, 7.25), fibrosis (SMD: -0.61 kPa; 95% CI: -1.12, -0.09 kPa), and liver enzymes including alanine transaminase (SMD: -0.86 U/L; 95% CI: -1.16, -0.56 U/L), aspartate transaminase (SMD: -0.87 U/L; 95% CI: -1.22, -0.52 U/L), and gamma-glutamyl transferase (SMD: -0.77 U/L; 95% CI: -1.26, -0.29 U/L). CONCLUSIONS Microbiome-targeted therapies were associated with significant improvements in liver-related outcomes in NAFLD patients. Nevertheless, limitations in existing literature like heterogeneity in probiotic strains, dosage, and formulation undermine our findings. This study was registered with PROSPERO (CRD42022354562) and supported by the Nanyang Technological University Start-up Grant and Wang Lee Wah Memorial Fund.
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Affiliation(s)
- Lim Rong
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Daniel Ch'ng
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Pingping Jia
- The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR
| | - Kelvin K F Tsoi
- The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR
- Stanley Ho Big Data Analytics Research Centre, The Chinese University of Hong Kong, Shatin, Hong Kong SAR
| | - Sunny H Wong
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Joseph J Y Sung
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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Zhou X, Wang J, Zhou S, Liao J, Ye Z, Mao L. Efficacy of probiotics on nonalcoholic fatty liver disease: A meta-analysis. Medicine (Baltimore) 2023; 102:e32734. [PMID: 36705359 PMCID: PMC9875992 DOI: 10.1097/md.0000000000032734] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 01/04/2023] [Indexed: 01/28/2023] Open
Abstract
OBJECTIVES The intestinal flora is closely related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). This study intends to systematically evaluate the efficacy and safety of probiotics in the treatment of NAFLD through a meta-analysis of published randomized controlled trials. METHODS This study was conducted through a search of published randomized controlled trials using probiotic-related drugs for the treatment of nonalcoholic fatty liver disease (up to April 6, 2022). The JADAD evaluation table was used to evaluate the quality of the literatures included in the search, and the risk of bias was evaluated according to the Cochrane evaluation manual. Finally, RevMan5.4 software was used for meta-analysis. RESULTS A total of 21 randomized clinical trials involving 1037 patients with NAFLD were included in this study. Meta-analysis results showed that after probiotic intervention, liver function, blood lipid level, blood glucose levels and insulin levels were significantly reduced, which had a good effect on improving hepatic steatosis. However, it did not significantly improve BMI, inflammatory factors, or homeostasis model assessment of insulin resistance. Through the subgroup analysis of the course of treatment, it was found that ALT, GGT, TG, and blood sugar improved better in the probiotic treatment course of greater than or equal to 12 weeks. CONCLUSION This study shows that the use of probiotics therapy has a good regulating effect on liver function, steatosis, blood glucose level, insulin level and blood lipid level in NAFLD patients.
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Affiliation(s)
- Xiangyu Zhou
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jincheng Wang
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Sufang Zhou
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Jiajia Liao
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Zuoyu Ye
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
- The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Leiming Mao
- Guizhou University of Traditional Chinese Medicine, Guiyang, China
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
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Al-Najjar Y, Arabi M, Paul P, Chaari A. Can probiotic, prebiotic, and synbiotic supplementation modulate the gut-liver axis in type 2 diabetes? A narrative and systematic review of clinical trials. Front Nutr 2022; 9:1052619. [PMID: 36532552 PMCID: PMC9751375 DOI: 10.3389/fnut.2022.1052619] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 11/16/2022] [Indexed: 07/25/2024] Open
Abstract
BACKGROUND Type 2 diabetes, one of the most common noncommunicable diseases, is a metabolic disorder that results in failed homeostatic control in several body systems, including hepatic function. Due to the gut microbiome's potential role in diabetes' pathogenesis, prebiotics, probiotics, and synbiotics have been proposed as complimentary therapeutic approaches aimed at microbiota readjustment. METHODS A systematic review was conducted on PubMed, Scopus, Web of Science, Embase, and the Cochrane Library examining the effect of probiotics, prebiotics, and synbiotics on hepatic biomarkers in patients with diabetes. RESULTS From 9,502 search hits, 10 studies met the inclusion criteria and were included in this review. A total of 816 participants (460 intervention and 356 control) were investigated for the effects of nine different hepatic biomarker measurements including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, bilirubin, liver steatosis, liver stiffness, fatty liver index, and gamma-glutamyl transferase levels. Of the 13 intervention groups analyzed from the 10 studies, 3 were prebiotic interventions, 3 were single species probiotic interventions, 3 were multi-species probiotic interventions, and 4 were synbiotic interventions. Nutraceuticals used in these trials included six genera of bacteria (Lactobacillus, Bifidobacterium, Streptococcus, Acetobacter, Lactococcus, and Propionibacterium), five different prebiotic formulations (inulin, inulin and beta carotene, chicory inulin enriched with oligofructose, galacto-oligosaccharides syrup, and powdered cinnamon), or a combination of these to form multi-species probiotics or synbiotics. CONCLUSION Although some studies showed insignificant changes in hepatic biomarkers, generally the results yielded a decrease in liver damage due to reduced oxidative stress, pro-inflammatory cytokines, gut dysbiosis, and insulin resistance which led to improvements in hepatic biomarker levels.
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Affiliation(s)
- Yousef Al-Najjar
- Medical Education Division, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation – Education City, Doha, Qatar
| | - Maryam Arabi
- Medical Education Division, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation – Education City, Doha, Qatar
| | - Pradipta Paul
- Medical Education Division, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation – Education City, Doha, Qatar
| | - Ali Chaari
- Premedical Division, Weill Cornell Medicine-Qatar, Qatar Foundation – Education City, Doha, Qatar
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Kobyliak N, Falalyeyeva T, Kyriachenko Y, Tseyslyer Y, Kovalchuk O, Hadiliia O, Eslami M, Yousefi B, Abenavoli L, Fagoonee S, Pellicano R. Akkermansia muciniphila as a novel powerful bacterial player in the treatment of metabolic disorders. Minerva Endocrinol (Torino) 2022; 47:242-252. [PMID: 35103461 DOI: 10.23736/s2724-6507.22.03752-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Abstract
Akkermansia muciniphila (A. muciniphila) is a mucin-degrading bacterium that commonly lives in the intestinal mucus layer. It is normally detected in human faecal specimens and is one of the few bacteria potentially associated to obesity development. In this narrative review, possible mechanisms that support how A. muciniphila is implicated in the pathogenesis of obesity and metabolic-associated disease are described with the evaluation of its role as an intermediary or independent agent whose manipulation could be useful in the management of metabolic disorders. The ampleness of A. muciniphila is notably diminished in obesity, type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), cardiometabolic diseases and low-grade inflammation. Furthermore, an inverse relationship between A. muciniphila, body weight and insulin sensitivity has been observed in both humans and animals. Antidiabetic drugs, gastric bypass surgery, prebiotics and biologically active compounds, such as polyphenols or saponins, have been shown to be associated with A. muciniphila relative abundance and thus could have favourable effects on metabolic disorders. Furthermore, A. muciniphila supplementation alone has been correlated with weight reduction and improvement of metabolic disorders, including fat mass gain, adipose tissue inflammation, metabolic endotoxaemia, and insulin resistance. Nevertheless, since the primary beneficial impacts of this bacterium have been predominantly investigated in various preclinical models, these results need to be confirmed in randomized clinical trials.
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Affiliation(s)
- Nazarii Kobyliak
- Department of Endocrinology, Bogomolets National Medical University, Kyiv, Ukraine -
- Medical Laboratory, CSD Health Care, Kyiv, Ukraine -
| | - Tetyana Falalyeyeva
- Medical Laboratory, CSD Health Care, Kyiv, Ukraine
- Taras Shevchenko National University, Kyiv, Ukraine
| | | | | | - Oleksandr Kovalchuk
- Taras Shevchenko National University, Kyiv, Ukraine
- Department of Human Anatomy, Bogomolets National Medical University, Kyiv, Ukraine
| | | | - Majid Eslami
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Bahman Yousefi
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Ludovico Abenavoli
- Department of Health Sciences, Magna Graecia University, Catanzaro, Italy
| | - Sharmila Fagoonee
- Institute of Biostructures and Bioimaging (CNR), Molecular Biotechnology Center, Turin, Italy
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette-S. Giovanni Antica Sede Hospital, Turin, Italy
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Paul P, Kaul R, Abdellatif B, Arabi M, Upadhyay R, Saliba R, Sebah M, Chaari A. The Promising Role of Microbiome Therapy on Biomarkers of Inflammation and Oxidative Stress in Type 2 Diabetes: A Systematic and Narrative Review. Front Nutr 2022; 9:906243. [PMID: 35711547 PMCID: PMC9197462 DOI: 10.3389/fnut.2022.906243] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 04/08/2022] [Indexed: 12/12/2022] Open
Abstract
Background One in 10 adults suffer from type 2 diabetes (T2D). The role of the gut microbiome, its homeostasis, and dysbiosis has been investigated with success in the pathogenesis as well as treatment of T2D. There is an increasing volume of literature reporting interventions of pro-, pre-, and synbiotics on T2D patients. Methods Studies investigating the effect of pro-, pre-, and synbiotics on biomarkers of inflammation and oxidative stress in T2D populations were extracted from databases such as PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to January 2022. Results From an initial screening of 5,984 hits, 47 clinical studies were included. Both statistically significant and non-significant results have been compiled, analyzed, and discussed. We have found various promising pro-, pre-, and synbiotic formulations. Of these, multistrain/multispecies probiotics are found to be more effective than monostrain interventions. Additionally, our findings show resistant dextrin to be the most promising prebiotic, followed closely by inulin and oligosaccharides. Finally, we report that synbiotics have shown excellent effect on markers of oxidative stress and antioxidant enzymes. We further discuss the role of metabolites in the resulting effects in biomarkers and ultimately pathogenesis of T2D, bring attention toward the ability of such nutraceuticals to have significant role in COVID-19 therapy, and finally discuss few ongoing clinical trials and prospects. Conclusion Current literature of pro-, pre- and synbiotic administration for T2D therapy is promising and shows many significant results with respect to most markers of inflammation and oxidative stress.
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Affiliation(s)
- Pradipta Paul
- Division of Medical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Ridhima Kaul
- Division of Medical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Basma Abdellatif
- Division of Medical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Maryam Arabi
- Division of Premedical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Rohit Upadhyay
- Department of Medicine—Nephrology and Hypertension, Tulane University, School of Medicine, New Orleans, LA, United States
| | - Reya Saliba
- Distributed eLibrary, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Majda Sebah
- Division of Premedical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
| | - Ali Chaari
- Division of Premedical Education, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar
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12
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Manzhalii E, Moyseyenko V, Kondratiuk V, Molochek N, Falalyeyeva T, Kobyliak N. Effect of a specific Escherichia coli Nissle 1917 strain on minimal/mild hepatic encephalopathy treatment. World J Hepatol 2022; 14:634-646. [PMID: 35582294 PMCID: PMC9055191 DOI: 10.4254/wjh.v14.i3.634] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/01/2021] [Accepted: 02/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE) can be considered a result of dysregulated gut-liver-brain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by "gut-centric" therapies, such as the administration of nonabsorbable disaccharides, nonabsorbable antibiotics, probiotics and prebiotics. AIM To assess the short-term efficacy and safety of the probiotic Escherichia coli Nissle (EcN) 1917 strain compared to lactulose and rifaximin in patients with minimal/mild HE. METHODS From January 2017 to March 2020, a total of 45 patients with HE were enrolled in this prospective, single-centre, open-label, randomized study. Participants were randomly assigned at a ratio of 1:1:1 to one of the treatment groups: The EcN group (n = 15), lactulose group (n = 15) or rifaximin group (n = 15) for a 1 mo intervention period. The main primary outcomes of the study were changes in serum ammonia and Stroop test score. The secondary outcomes were markers of a chronic systemic inflammatory response (ІL-6, ІL-8, and IFN-γ) and bacteriology of the stool flora evaluated by specialized nonculture techniques after a 1 mo intervention period. RESULTS Patients who were given rifaximin or EcN showed a more significant reduction in serum ammonia and normalization of Bifidobacteria and Lactobacilli abundance compared to the lactulose group. However, the most pronounced restoration of the symbiotic microflora was associated with EcN administration and characterized by the absence of E. coli with altered properties and pathogenic enterobacteria in patient faeces. In the primary outcome analysis, improvements in the Stroop test parameters in all intervention groups were observed. Moreover, EcN-treated patients performed 15% faster on the Stroop test than the lactulose group patients (P = 0.017). Both EcN and rifaximin produced similar significant reductions in the proinflammatory cytokines INF-γ, IL-6 and IL-8. EcN was more efficient than lactulose in reducing proinflammatory cytokine levels. CONCLUSION The use of the probiotic EcN strain was safe and quite efficient for HE treatment. The probiotic reduced the ammonia content and the level of serum proinflammatory cytokines, normalized the gut microbiota composition and improved the cognitive function of patients with HE. The application of the EcN strain was more effective than lactulose treatment.
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Affiliation(s)
- Elina Manzhalii
- Department of Propedeutics of Internal Medicine, Bogomolets National Medical University, Kyiv 01601, Ukraine.
| | - Valentyna Moyseyenko
- Department of Propedeutics of Internal Medicine, Bogomolets National Medical University, Kyiv 01601, Ukraine
| | - Vitalii Kondratiuk
- Department of Propedeutics of Internal Medicine, Bogomolets National Medical University, Kyiv 01601, Ukraine
| | - Nataliia Molochek
- Educational and Scientific Centre “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine
- Department of Pediatrics, Bogomolets National Medical University, Kyiv 01601, Ukraine
| | - Tetyana Falalyeyeva
- Educational and Scientific Centre “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine
- Department of Scientific, Medical Laboratory CSD, Kyiv 01004, Ukraine
| | - Nazarii Kobyliak
- Department of Endocrinology, Bogomolets National Medical University, Kyiv 01601, Ukraine
- Department of Scientific, Medical Laboratory CSD, Kyiv 01004, Ukraine.
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KAMINSKY R, YANCHYSHYN A, BELEMETS N, KURYK O, SAMBORSKA I, DZEVULSKA I, PELLICANO R. Hyperhomocysteinemia in the pathogenesis of cardiovascular and endocrine diseases: translational messages. MINERVA BIOTECHNOLOGY AND BIOMOLECULAR RESEARCH 2022; 34. [DOI: 10.23736/s2724-542x.21.02805-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
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14
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Current Status and Future Therapeutic Options for Fecal Microbiota Transplantation. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58010084. [PMID: 35056392 PMCID: PMC8780626 DOI: 10.3390/medicina58010084] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 12/23/2021] [Accepted: 01/04/2022] [Indexed: 12/12/2022]
Abstract
The intestinal microbiota plays an important role in maintaining human health, and its alteration is now associated with the development of various gastrointestinal (ulcerative colitis, irritable bowel syndrome, constipation, etc.) and extraintestinal diseases, such as cancer, metabolic syndrome, neuropsychiatric diseases. In this context, it is not surprising that gut microbiota modification methods may constitute a therapy whose potential has not yet been fully investigated. In this regard, the most interesting method is thought to be fecal microbiota transplantation, which consists of the simultaneous replacement of the intestinal microbiota of a sick recipient with fecal material from a healthy donor. This review summarizes the most interesting findings on the application of fecal microbiota transplantation in gastrointestinal and extraintestinal pathologies.
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15
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Falalyeyeva T, Mamula Y, Scarpellini E, Leshchenko I, Humeniuk A, Pankiv I, Kobyliak N. Probiotics and obesity associated disease: an extended view beyond traditional strains. Minerva Gastroenterol (Torino) 2021; 67:348-356. [PMID: 35040301 DOI: 10.23736/s2724-5985.21.02909-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Interaction between intestinal microbiota and obesity is becoming abundantly according to current many scientific investigations. In this article, probiotic therapy was offered as the promising strategy of metabolic disorders control through the recovery of microbiota composition and health maintenance with the help of impact on the abovementioned mechanisms. First, this therapy is safe, with minimal side effects, well-tolerated, and appropriate for long-term use. Second, it can improve body mass, glucose, and fat metabolism, increase insulin sensitivity, and decrease systemic chronic inflammation. In conclusion, the restorative role of gut microbiota on metabolic disorders and associated diseases could open new ways in the treatment of obesity, insulin resistance, and type 2 diabetes.
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Affiliation(s)
- Tetyana Falalyeyeva
- Institute of Biology and Medicine, Educational and Scientific Center, Taras Shevchenko National University, Kyiv, Ukraine
| | - Yelyzaveta Mamula
- Institute of Biology and Medicine, Educational and Scientific Center, Taras Shevchenko National University, Kyiv, Ukraine
| | - Emidio Scarpellini
- Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University, Leuven, Belgium
| | - Ivan Leshchenko
- Department of Physiology, Bogomolets National Medical University, Kyiv, Ukraine
| | - Alla Humeniuk
- Department of Physiology, Bogomolets National Medical University, Kyiv, Ukraine
| | - Ivan Pankiv
- Department of Clinical Immunology, Allergology and Endocrinology, Bukovinian State Medical University, Chernivtsi, Ukraine
| | - Nazarii Kobyliak
- Department of Endocrinology, Bogomolets National Medical University, Kyiv, Ukraine -
- Medical Laboratory CSD, Kyiv, Ukraine
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FALALYEYEVA T, KOMISARENKO I, YANCHYSHYN A, KOVALCHUK O, LOZKO Y, TSYRYUK O, FAGOONEE S, KOBYLIAK N. Vitamin D in the prevention and treatment of type-2 diabetes and associated diseases: a critical view during COVID-19 time. MINERVA BIOTECHNOLOGY AND BIOMOLECULAR RESEARCH 2021; 33. [DOI: 10.23736/s2724-542x.21.02766-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/10/2025]
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BAHMAN Y, MARYAM M, AISA B, FALALYEYEVA T, KOBYLIAK N, MAJID E. Immunomodulatory role of Faecalibacterium prausnitzii in obesity and metabolic disorders. MINERVA BIOTECHNOLOGY AND BIOMOLECULAR RESEARCH 2021. [DOI: 10.23736/s2724-542x.21.02759-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Eslami M, Bahar A, Hemati M, Rasouli Nejad Z, Mehranfar F, Karami S, Kobyliak NM, Yousefi B. Dietary pattern, colonic microbiota and immunometabolism interaction: new frontiers for diabetes mellitus and related disorders. Diabet Med 2021; 38:e14415. [PMID: 33025587 DOI: 10.1111/dme.14415] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 09/10/2020] [Accepted: 09/20/2020] [Indexed: 12/18/2022]
Abstract
In this review, the numerous possible mechanisms that provide supportive evidence for how colonic dysbiosis denotes metabolic dysfunction, dysregulates glucose homeostasis and leads to diabetes mellitus and related metabolic disorders are defined. Information was gathered from articles identified by systematic reviews and searches using Google, PubMed and Scopus. The composition of the colonic microbiota plays an integral role in maintaining host homeostasis by affecting both metabolic activities and underlying functional gene transcription in individuals with diabetes and related metabolic disorders. Increased colonic microbiome-derived concentrations of lipopolysaccharides, also known as 'metabolic endotoxaemia', as well as alterations in bile acid metabolism, short-chain fatty acids, intestinal hormones and branched-chain amino acid secretion have been associated with the diverse production of pro-inflammatory cytokines and the recruitment of inflammatory cells. It has been shown that changes to intestinal bacterial composition are significant even in early childhood and are associated with the pathogenesis of both types of diabetes. We hope that an improved understanding of related mechanisms linking the colonic microbiome with glucose metabolism might provide for innovative therapeutic approaches that would bring the ideal intestinal ecosystem to a state of optimal health, thus preventing and treating diabetes and related metabolic disorders.
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Affiliation(s)
- M Eslami
- Cancer Research Center, Semnan, Iran
| | - A Bahar
- Department of Biochemistry, Semnan, Iran
| | - M Hemati
- Department of Immunology, Semnan, Iran
| | | | - F Mehranfar
- Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran
| | - S Karami
- Department of Biochemistry, Semnan, Iran
| | - N M Kobyliak
- Department of Endocrinology, Bogomolets National Medical University, Kyiv, Ukraine
| | - B Yousefi
- Department of Immunology, Semnan, Iran
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Probiotic Composition and Chondroitin Sulfate Regulate TLR-2/4-Mediated NF-κB Inflammatory Pathway and Cartilage Metabolism in Experimental Osteoarthritis. Probiotics Antimicrob Proteins 2021; 13:1018-1032. [PMID: 33459997 DOI: 10.1007/s12602-020-09735-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2020] [Indexed: 02/07/2023]
Abstract
The therapeutic potential of using probiotics to treat osteoarthritis (OA) has only recently been recognized, with a small number of animal and human studies having been undertaken. The aim of this study was to describe the effect of a probiotic composition (PB) and chondroitin sulfate (CS), administered separately or in combination, on Tlr2, Tlr4, Nfkb1, and Comp gene expression in cartilage and levels of cytokines (IL-6, IL-8, TGF-β1, IGF-1) and COMP, ACAN, CHI3L1, CTSK, and TLR-2 in serum during monoiodoacetate (MIA)-induced OA in rats. Expression of Tlr2, Tlr4, Nfkb1, and Comp in cartilage was analyzed using one-step SYBR Green real-time RT-PCR. The levels of IL-6, IL-8, TGF-β1, IGF-1, COMP, ACAN, CHI3L1, CTSK, and TLR-2 were measured in serum by enzyme-linked immunosorbent assay. Experimental OA caused an upregulation in Tlr2, Tlr4, Nfkb1, and downregulation of Comp expression in the cartilage. MIA-OA caused a significant increase of TLR-2 soluble form and IL-6, IL-8, TGF-β1, COMP, ACAN, CHI3L1, and CTSK levels in the blood serum; the level of IGF-1, on contrary, decreased. Separate administration of PB and CS raised expression of Comp and reduced Tlr2, Tlr4, and Nfkb1 expressions in cartilage. The levels of the studied markers of cartilage metabolism in serum were decreased or increased (IGF-1). The combined use of PB and CS was more effective than separate application approaching above-mentioned parameters to control. The outcomes of our research prove that multistrain live probiotic composition amplifies the positive action of CS in osteoarthritis attenuation and necessitates further investigation with large-scale randomized controlled trial.
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Kobyliak N, Falalyeyeva T, Mykhalchyshyn G, Molochek N, Savchuk O, Kyriienko D, Komisarenko I. Probiotic and omega-3 polyunsaturated fatty acids supplementation reduces insulin resistance, improves glycemia and obesity parameters in individuals with type 2 diabetes: A randomised controlled trial. ACTA ACUST UNITED AC 2020. [DOI: 10.1016/j.obmed.2020.100248] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Kobyliak N, Falalyeyeva T, Tsyryuk O, Eslami M, Kyriienko D, Beregova T, Ostapchenko L. New insights on strain-specific impacts of probiotics on insulin resistance: evidence from animal study. J Diabetes Metab Disord 2020; 19:289-296. [PMID: 32550178 PMCID: PMC7270447 DOI: 10.1007/s40200-020-00506-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 02/05/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS сomparative animal study of effectiveness of intermittent administration of lyophilized single-, three- and alive multistrain probiotic in short courses on insulin resistance (IR) in rats with experimental obesity. METHODS 70 rats were divided into 7 groups (n = 10 in each). Rats of group I were left intact. Newborn rats in groups II-VII were administered monosodium glutamate (MSG) (4 mg/g) by injection. Rats in group II (MSG-obesity group) were left untreated. The rats in groups III-V received lyophilized mono-probiotics B.animalis VKL, B.animalis VKB, L.casei IMVB-7280 respectively. The rats in group VI received all three of these probiotic strains mixed together. Group VII was treated with multi-probiotic "Symbiter", containing 14 different live probiotic strains (Lactobacillus, Bifidobacterium, Propionibacterium, Acetobacter genera). RESULTS Treatment of newborn rats with MSG lead to the development of obesity in all MSG-obesity rats and up to 20-70% after probiotic administration. Additions to probiotic composition, with preference to alive strains (group VII), led to significantly lower rates of obesity, decrease in HOMA-IR (p < 0.001), proinflammatory cytokines levels - IL-1β (p = 0.003), IL-12Bp40 (p < 0.001) and elevation of adiponectin (p = 0.003), TGF-β (p = 0.010) in comparison with MSG-obesity group. Analysis of results in groups treated with single-strain probiotics (groups III-V) shows significant decrease in HOMA-IR, but changes were less pronounced as compared to mixture groups and did not achieve intact rats level. Other metabolic parameters were not affected significantly by single strains. CONCLUSION Our findings provide major clues for how to design and use probiotics with more efficient compositions in obesity and IR management and may bring new insights into how host-microbe interactions contribute to such protective effects.
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Affiliation(s)
- Nazarii Kobyliak
- Department Endocrinology, Bogomolets National Medical University, T. Shevchenko boulevard, 13, Kyiv, 01601 Ukraine
| | - Tetyana Falalyeyeva
- Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601 Ukraine
| | - Olena Tsyryuk
- Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601 Ukraine
| | - Majid Eslami
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | | | - Tetyana Beregova
- Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601 Ukraine
| | - Liudmila Ostapchenko
- Taras Shevchenko National University of Kyiv, Volodymyrska Str., 64/13, Kyiv, 01601 Ukraine
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