TY  - JOUR
AU  - Mitrović, Miloš
AU  - Stanković-Popović, Verica
AU  - Tolinački, Maja
AU  - Golić, Nataša
AU  - Soković Bajić, Svetlana
AU  - Veljović, Katarina
AU  - Nastasijević, Branislav
AU  - Soldatović, Ivan
AU  - Svorcan, Petar
AU  - Dimković, Nada
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S1051227622001522
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1753
AB  - ObjectiveAltering dysbiotic gut flora through synbiotic supplementation has recently been recognized as a potential treatment strategy to reduce the levels of gut-derived uremic toxins and decrease inflammation. Assessing its efficacy and safety has been the main goal of our randomized, double-blind, placebo-controlled study.MethodsA total of 34 nondialyzed chronic kidney disease patients, aged ≥18 years, with an estimated glomerular filtration rate between 15 and 45 mL/minute, were randomized either to an intervention group (n = 17), receiving synbiotic (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium lactis, 32 billion colony forming units per day plus 3.2 g of inulin), or control group (n = 17), receiving placebo during 12 weeks. The impact of treatment on the dynamic of serum levels of gut-derived uremic toxins, total serum indoxyl sulfate, p-cresyl sulfate, and trimethylamine N-oxide, was defined as the primary outcome of the study. Secondary outcomes included changes in the stool microbiome, serum interleukin-6 levels, high-sensitivity C-reactive protein, estimated glomerular filtration rate, albuminuria, diet, gastrointestinal symptom dynamics, and safety. Serum levels of uremic toxins were determined using ultraperformance liquid chromatography. The stool microbiome analysis was performed using the 16S ribosomal ribonucleic acid gene sequencing approach.ResultsSynbiotic treatment significantly modified gut microbiome with Bifidobacteria, Lactobacillus, and Subdoligranulum genera enrichment and consequently reduced serum level of indoxyl sulfate (ΔIS –21.5% vs. 5.3%, P < .001), improved estimated glomerular filtration rate (ΔeGFR 12% vs. 8%, P = .029), and decreased level of high-sensitivity C-reactive protein (–39.5 vs. –8.5%, P < .001) in treated patients. Two patients of the intervention arm complained of increased flatulence. No other safety issues were noted.ConclusionSynbiotics could be available, safe, and an effective therapeutic strategy we could use in daily practice in order to decrease levels of uremic toxins and microinflammation in chronic kidney disease patients.
T2  - Journal of Renal Nutrition
T2  - Journal of Renal NutritionJournal of Renal Nutrition
T1  - The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial
EP  - 288
IS  - 2
SP  - 278
VL  - 33
DO  - 10.1053/j.jrn.2022.07.008
ER  - 

@article{
author = "Mitrović, Miloš and Stanković-Popović, Verica and Tolinački, Maja and Golić, Nataša and Soković Bajić, Svetlana and Veljović, Katarina and Nastasijević, Branislav and Soldatović, Ivan and Svorcan, Petar and Dimković, Nada",
year = "2023",
abstract = "ObjectiveAltering dysbiotic gut flora through synbiotic supplementation has recently been recognized as a potential treatment strategy to reduce the levels of gut-derived uremic toxins and decrease inflammation. Assessing its efficacy and safety has been the main goal of our randomized, double-blind, placebo-controlled study.MethodsA total of 34 nondialyzed chronic kidney disease patients, aged ≥18 years, with an estimated glomerular filtration rate between 15 and 45 mL/minute, were randomized either to an intervention group (n = 17), receiving synbiotic (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium lactis, 32 billion colony forming units per day plus 3.2 g of inulin), or control group (n = 17), receiving placebo during 12 weeks. The impact of treatment on the dynamic of serum levels of gut-derived uremic toxins, total serum indoxyl sulfate, p-cresyl sulfate, and trimethylamine N-oxide, was defined as the primary outcome of the study. Secondary outcomes included changes in the stool microbiome, serum interleukin-6 levels, high-sensitivity C-reactive protein, estimated glomerular filtration rate, albuminuria, diet, gastrointestinal symptom dynamics, and safety. Serum levels of uremic toxins were determined using ultraperformance liquid chromatography. The stool microbiome analysis was performed using the 16S ribosomal ribonucleic acid gene sequencing approach.ResultsSynbiotic treatment significantly modified gut microbiome with Bifidobacteria, Lactobacillus, and Subdoligranulum genera enrichment and consequently reduced serum level of indoxyl sulfate (ΔIS –21.5% vs. 5.3%, P < .001), improved estimated glomerular filtration rate (ΔeGFR 12% vs. 8%, P = .029), and decreased level of high-sensitivity C-reactive protein (–39.5 vs. –8.5%, P < .001) in treated patients. Two patients of the intervention arm complained of increased flatulence. No other safety issues were noted.ConclusionSynbiotics could be available, safe, and an effective therapeutic strategy we could use in daily practice in order to decrease levels of uremic toxins and microinflammation in chronic kidney disease patients.",
journal = "Journal of Renal Nutrition, Journal of Renal NutritionJournal of Renal Nutrition",
title = "The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial",
pages = "288-278",
number = "2",
volume = "33",
doi = "10.1053/j.jrn.2022.07.008"
}

Mitrović, M., Stanković-Popović, V., Tolinački, M., Golić, N., Soković Bajić, S., Veljović, K., Nastasijević, B., Soldatović, I., Svorcan, P.,& Dimković, N.. (2023). The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial. in Journal of Renal Nutrition, 33(2), 278-288.
https://doi.org/10.1053/j.jrn.2022.07.008

Mitrović M, Stanković-Popović V, Tolinački M, Golić N, Soković Bajić S, Veljović K, Nastasijević B, Soldatović I, Svorcan P, Dimković N. The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial. in Journal of Renal Nutrition. 2023;33(2):278-288.
doi:10.1053/j.jrn.2022.07.008 .

Mitrović, Miloš, Stanković-Popović, Verica, Tolinački, Maja, Golić, Nataša, Soković Bajić, Svetlana, Veljović, Katarina, Nastasijević, Branislav, Soldatović, Ivan, Svorcan, Petar, Dimković, Nada, "The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial" in Journal of Renal Nutrition, 33, no. 2 (2023):278-288,
https://doi.org/10.1053/j.jrn.2022.07.008 . .

TY  - JOUR
AU  - Protić, Marijana B.
AU  - Pavlović, Sonja
AU  - Bojić, Daniela Z.
AU  - Krstić, Miodrag N.
AU  - Radojicić, Zoran A.
AU  - Tarabar, Dino K.
AU  - Stevanović, Ana Z.
AU  - Karan-Đurašević, Teodora
AU  - Godjevac, Mina V.
AU  - Svorcan, Petar V.
AU  - Dapcević, Branka D.
AU  - Jojić, Njegica Z.
PY  - 2008
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/335
AB  - Objective Genetic heterogeneity and incomplete phenotype penetrance complicate genetic analysis of Crohn's disease (M. Studies in western Europe have shown that CARD15 polymorphisms increase susceptibility to CD, but frequencies vary within different European populations. The aim here was to evaluate the prevalence of CARD15 mutations and their phenotypic correlation in a Serbian population. Materials and methods 131 patients with CD, 65 patients with ulcerative colitis, and 88 healthy controls were genotyped for three common mutations (R702W, G908R, Leu1007insC) by PCR-restriction fragment length polymorphism. chi(2) and Student's t-test were used for statistical assessment. Results At least one CARD15 disease-associated allele was found in 35.11 % patients with CD, 14.77% of healthy controls (P=0.001), and 7.69% patients with ulcerative colitis (P= 0.0001). The L1007fs mutation showed a significant association with CD (P lt 0.0001). The frequency of R702W mutant allele was almost equal in the control group and CD patients Univariate analyses established that CARD15 carriers had a significantly higher risk of isolated ileal location [P=0.042; odds ratio (OR) 2.30; 95% confidence interval (CI): 1.02-5.191, fibrostenotic behavior (P lt 0.0001; OR 9.86; 95% CI: 4.29-22.62), surgical resection (P=0.036; OR 2.2; CI, 1.046-4.626), and earlier onset of disease (P=0.026). Conclusion This study confirms that CARD15 carriers, especially L1007fs mutants, in central Europeans have an increased risk of CD and it is associated with earlier onset, ileal, fibrostenotic disease and a higher risk of surgery. Any influence of latitude is not matched by an east-west divide on the genotype frequency and phenotype of CD within Europe.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - European Journal of Gastroenterology & Hepatology
T1  - CARD15 gene polyrnorphisms in Serbian patients with Crohn's disease: genotype-phenotype analysis
EP  - 984
IS  - 10
SP  - 978
VL  - 20
DO  - 10.1097/MEG.0b013e328302f45e
ER  - 

@article{
author = "Protić, Marijana B. and Pavlović, Sonja and Bojić, Daniela Z. and Krstić, Miodrag N. and Radojicić, Zoran A. and Tarabar, Dino K. and Stevanović, Ana Z. and Karan-Đurašević, Teodora and Godjevac, Mina V. and Svorcan, Petar V. and Dapcević, Branka D. and Jojić, Njegica Z.",
year = "2008",
abstract = "Objective Genetic heterogeneity and incomplete phenotype penetrance complicate genetic analysis of Crohn's disease (M. Studies in western Europe have shown that CARD15 polymorphisms increase susceptibility to CD, but frequencies vary within different European populations. The aim here was to evaluate the prevalence of CARD15 mutations and their phenotypic correlation in a Serbian population. Materials and methods 131 patients with CD, 65 patients with ulcerative colitis, and 88 healthy controls were genotyped for three common mutations (R702W, G908R, Leu1007insC) by PCR-restriction fragment length polymorphism. chi(2) and Student's t-test were used for statistical assessment. Results At least one CARD15 disease-associated allele was found in 35.11 % patients with CD, 14.77% of healthy controls (P=0.001), and 7.69% patients with ulcerative colitis (P= 0.0001). The L1007fs mutation showed a significant association with CD (P lt 0.0001). The frequency of R702W mutant allele was almost equal in the control group and CD patients Univariate analyses established that CARD15 carriers had a significantly higher risk of isolated ileal location [P=0.042; odds ratio (OR) 2.30; 95% confidence interval (CI): 1.02-5.191, fibrostenotic behavior (P lt 0.0001; OR 9.86; 95% CI: 4.29-22.62), surgical resection (P=0.036; OR 2.2; CI, 1.046-4.626), and earlier onset of disease (P=0.026). Conclusion This study confirms that CARD15 carriers, especially L1007fs mutants, in central Europeans have an increased risk of CD and it is associated with earlier onset, ileal, fibrostenotic disease and a higher risk of surgery. Any influence of latitude is not matched by an east-west divide on the genotype frequency and phenotype of CD within Europe.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "European Journal of Gastroenterology & Hepatology",
title = "CARD15 gene polyrnorphisms in Serbian patients with Crohn's disease: genotype-phenotype analysis",
pages = "984-978",
number = "10",
volume = "20",
doi = "10.1097/MEG.0b013e328302f45e"
}

Protić, M. B., Pavlović, S., Bojić, D. Z., Krstić, M. N., Radojicić, Z. A., Tarabar, D. K., Stevanović, A. Z., Karan-Đurašević, T., Godjevac, M. V., Svorcan, P. V., Dapcević, B. D.,& Jojić, N. Z.. (2008). CARD15 gene polyrnorphisms in Serbian patients with Crohn's disease: genotype-phenotype analysis. in European Journal of Gastroenterology & Hepatology
Lippincott Williams & Wilkins, Philadelphia., 20(10), 978-984.
https://doi.org/10.1097/MEG.0b013e328302f45e

Protić MB, Pavlović S, Bojić DZ, Krstić MN, Radojicić ZA, Tarabar DK, Stevanović AZ, Karan-Đurašević T, Godjevac MV, Svorcan PV, Dapcević BD, Jojić NZ. CARD15 gene polyrnorphisms in Serbian patients with Crohn's disease: genotype-phenotype analysis. in European Journal of Gastroenterology & Hepatology. 2008;20(10):978-984.
doi:10.1097/MEG.0b013e328302f45e .

Protić, Marijana B., Pavlović, Sonja, Bojić, Daniela Z., Krstić, Miodrag N., Radojicić, Zoran A., Tarabar, Dino K., Stevanović, Ana Z., Karan-Đurašević, Teodora, Godjevac, Mina V., Svorcan, Petar V., Dapcević, Branka D., Jojić, Njegica Z., "CARD15 gene polyrnorphisms in Serbian patients with Crohn's disease: genotype-phenotype analysis" in European Journal of Gastroenterology & Hepatology, 20, no. 10 (2008):978-984,
https://doi.org/10.1097/MEG.0b013e328302f45e . .