TY  - CONF
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Ilić, Nataša
AU  - Đokić, Jelena
AU  - Stojanović, Dušica
AU  - Vasilev, Saša
AU  - Gruden-Movsesijan, Alisa
AU  - Tomić, Sergej
PY  - 2023
UR  - https://www.microbiota-site.com/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2188
AB  - ntroduction: Recent studies implicated overactivated myeloid cells and gut microbiome, along with our work, 
in multiple sclerosis (MS) pathogenesis. As we have shown before, prostaglandin (PG)E2 promotes 
suppressive properties of myeloid cells leading to amelioration of symptoms in myelin oligodendrocyte 
glycoprotein 
(MOG)-induced experimental autoimmune encephalomyelitis 
(EAE). Additionally, we 
investigated how the changes of gut microbiota associate with EAE and the effects of therapy.
Materials & Methods: MOG35-55 in Complete Freund Adjuvans was used for EAE induction in C57BL/6 
mice. Gold nanoparticles (GNP) conjugated with PGE2 and MOG were applied on the day 1, 3, 5, 7, and 9 
post-immunization. We performed extensive immunophenotyping and metagenomic analysis in order to 
decipher association between gut microbiome and efficacy of GNP-MOG-PGE2 treatment.
Results: GNP-MOG-PGE2 treatment alleviates EAE symptoms, decreased levels of pro-inflammatory 
cytokines in sera, and increased proportion of suppressive MDSCs in CNS-infiltrates. Furthermore, EAE 
induction significantly affected species richness, while GNP-MOG-PGE2 treatment increased the gut 
microbiota diversity and preserved the richness of species with immunomodulatory properties.
Conclusion: Taken together, our data indicate that targeted activation of myeloid cells by GNP-MOG-PGE2 
together with gut microbiota modification is very promising therapeutic strategy for MS.
C3  - 10th ISM World Congress on Targeting Microbiota
T1  - NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION
EP  - 77
SP  - 77
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2188
ER  - 

@conference{
author = "Radojević, Dušan and Bekić, Marina and Ilić, Nataša and Đokić, Jelena and Stojanović, Dušica and Vasilev, Saša and Gruden-Movsesijan, Alisa and Tomić, Sergej",
year = "2023",
abstract = "ntroduction: Recent studies implicated overactivated myeloid cells and gut microbiome, along with our work, 
in multiple sclerosis (MS) pathogenesis. As we have shown before, prostaglandin (PG)E2 promotes 
suppressive properties of myeloid cells leading to amelioration of symptoms in myelin oligodendrocyte 
glycoprotein 
(MOG)-induced experimental autoimmune encephalomyelitis 
(EAE). Additionally, we 
investigated how the changes of gut microbiota associate with EAE and the effects of therapy.
Materials & Methods: MOG35-55 in Complete Freund Adjuvans was used for EAE induction in C57BL/6 
mice. Gold nanoparticles (GNP) conjugated with PGE2 and MOG were applied on the day 1, 3, 5, 7, and 9 
post-immunization. We performed extensive immunophenotyping and metagenomic analysis in order to 
decipher association between gut microbiome and efficacy of GNP-MOG-PGE2 treatment.
Results: GNP-MOG-PGE2 treatment alleviates EAE symptoms, decreased levels of pro-inflammatory 
cytokines in sera, and increased proportion of suppressive MDSCs in CNS-infiltrates. Furthermore, EAE 
induction significantly affected species richness, while GNP-MOG-PGE2 treatment increased the gut 
microbiota diversity and preserved the richness of species with immunomodulatory properties.
Conclusion: Taken together, our data indicate that targeted activation of myeloid cells by GNP-MOG-PGE2 
together with gut microbiota modification is very promising therapeutic strategy for MS.",
journal = "10th ISM World Congress on Targeting Microbiota",
title = "NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION",
pages = "77-77",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2188"
}

Radojević, D., Bekić, M., Ilić, N., Đokić, J., Stojanović, D., Vasilev, S., Gruden-Movsesijan, A.,& Tomić, S.. (2023). NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION. in 10th ISM World Congress on Targeting Microbiota, 77-77.
https://hdl.handle.net/21.15107/rcub_imagine_2188

Radojević D, Bekić M, Ilić N, Đokić J, Stojanović D, Vasilev S, Gruden-Movsesijan A, Tomić S. NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION. in 10th ISM World Congress on Targeting Microbiota. 2023;:77-77.
https://hdl.handle.net/21.15107/rcub_imagine_2188 .

Radojević, Dušan, Bekić, Marina, Ilić, Nataša, Đokić, Jelena, Stojanović, Dušica, Vasilev, Saša, Gruden-Movsesijan, Alisa, Tomić, Sergej, "NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION" in 10th ISM World Congress on Targeting Microbiota (2023):77-77,
https://hdl.handle.net/21.15107/rcub_imagine_2188 .

TY  - CONF
AU  - Bekić, Marina
AU  - Đokić, Jelena
AU  - Radojević, Dušan
AU  - Vučević, Dragana
AU  - Vasilev, Saša
AU  - Tomić, Sergej
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2042
AB  - Although genetic predisposition to Multiple Sclerosis (MS) may play an essential role in disease
development, myeloid cell overactivation and gut microbiota dysbiosis are key contributors to MS
pathogenesis. Myeloid-Derived Suppressor Cells (MDSC)s are immature myeloid cells with strong
immunosuppressive functions which can be exploited in the treatment of autoimmune diseases.
Considering the limited data on MDSCs application in MS therapy and their poorly studied effects
on the gut microbiota, we have investigated the therapeutic potential of mice MDSC differentiated
according to the standard protocol (MDSC) and modified with the addition of prostaglandin (PG)
E2 (MDSC-PGE2) to ameliorate experimental autoimmune encephalomyelitis (EAE) induced with
MOG35-55/CFA/PtX in C57BL/6 mice. Additionally, we analyzed the changes in gut microbiota
features in control and MDSC-treated animals by using a shotgun metagenomics approach. In
mice, PGE2-activated MDSC significantly inhibited the onset and clinical course of EAE. This effect
correlated with increased IL-10, TGF-β, IL-4 production, and Arginase-1 level in MDSC-PGE2,
as well as with reduced leukocyte infiltrates in the spinal cord. MDSC-PGE2 protective effect is
also reflected in the maintenance of gut microbiota composition based on Kraken2/Bracken2
and LEfSe analysis. We observed an increase of MS-associated species Romboutsia ilealis in
the control EAE group, while in both MDSC treatments the increase in relative abundances of
Muribaculum gordoncarteri and Duncaniella dubiosis, associated with immunoregulatory properties,
was observed. Microbial metabolic pathways profiling using Humann3 pipeline also reveals the
increase in pathways involved in the production of potentially immunoregulatory metabolites
in the MDSC-PGE2 group. In conclusion, we pointed to the significant association between the
efficacy of MDSC-PGE2 treatment and gut microbiota features which can be further exploited in
order to improve MDSC-based EAE therapy.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation
EP  - 97
SP  - 97
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2042
ER  - 

@conference{
author = "Bekić, Marina and Đokić, Jelena and Radojević, Dušan and Vučević, Dragana and Vasilev, Saša and Tomić, Sergej",
year = "2023",
abstract = "Although genetic predisposition to Multiple Sclerosis (MS) may play an essential role in disease
development, myeloid cell overactivation and gut microbiota dysbiosis are key contributors to MS
pathogenesis. Myeloid-Derived Suppressor Cells (MDSC)s are immature myeloid cells with strong
immunosuppressive functions which can be exploited in the treatment of autoimmune diseases.
Considering the limited data on MDSCs application in MS therapy and their poorly studied effects
on the gut microbiota, we have investigated the therapeutic potential of mice MDSC differentiated
according to the standard protocol (MDSC) and modified with the addition of prostaglandin (PG)
E2 (MDSC-PGE2) to ameliorate experimental autoimmune encephalomyelitis (EAE) induced with
MOG35-55/CFA/PtX in C57BL/6 mice. Additionally, we analyzed the changes in gut microbiota
features in control and MDSC-treated animals by using a shotgun metagenomics approach. In
mice, PGE2-activated MDSC significantly inhibited the onset and clinical course of EAE. This effect
correlated with increased IL-10, TGF-β, IL-4 production, and Arginase-1 level in MDSC-PGE2,
as well as with reduced leukocyte infiltrates in the spinal cord. MDSC-PGE2 protective effect is
also reflected in the maintenance of gut microbiota composition based on Kraken2/Bracken2
and LEfSe analysis. We observed an increase of MS-associated species Romboutsia ilealis in
the control EAE group, while in both MDSC treatments the increase in relative abundances of
Muribaculum gordoncarteri and Duncaniella dubiosis, associated with immunoregulatory properties,
was observed. Microbial metabolic pathways profiling using Humann3 pipeline also reveals the
increase in pathways involved in the production of potentially immunoregulatory metabolites
in the MDSC-PGE2 group. In conclusion, we pointed to the significant association between the
efficacy of MDSC-PGE2 treatment and gut microbiota features which can be further exploited in
order to improve MDSC-based EAE therapy.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation",
pages = "97-97",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2042"
}

Bekić, M., Đokić, J., Radojević, D., Vučević, D., Vasilev, S.,& Tomić, S.. (2023). Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 97-97.
https://hdl.handle.net/21.15107/rcub_imagine_2042

Bekić M, Đokić J, Radojević D, Vučević D, Vasilev S, Tomić S. Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation. in 4th Belgrade Bioinformatics Conference. 2023;4:97-97.
https://hdl.handle.net/21.15107/rcub_imagine_2042 .

Bekić, Marina, Đokić, Jelena, Radojević, Dušan, Vučević, Dragana, Vasilev, Saša, Tomić, Sergej, "Shotgun metagenomics reveals gut microbiota features associated with the efficacy of myeloid derived suppressor cells in the prevention of neuroinflammation" in 4th Belgrade Bioinformatics Conference, 4 (2023):97-97,
https://hdl.handle.net/21.15107/rcub_imagine_2042 .

TY  - CONF
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Gruden-Movsesijan, Alisa
AU  - Ilić, Nataša
AU  - Vasilev, Saša
AU  - Dinić, Miroslav
AU  - Golić, Nataša
AU  - Vučević, Dragana
AU  - Čolić, Miodrag
AU  - Tomić, Sergej
AU  - Đokić, Jelena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1875
AB  - The role of gut microbiota composition in efficacy of various immune-based therapies is increasingly recognized.
Thus, the aim of our study was to investigate if the efficacy of myeloid-derived suppressor cells
(MDSC)-Prostaglandin E2 (PGE2) therapy for multiple sclerosis (MS) correlates with gut microbiota composition
and function. MDSC generated from bone marrow cells in the presence of PGE2 were applied to spinal
cord homogenate/CFA-induced experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA)
rats, an animal model of MS. MDSC-PGE2 therapy resulted in a significant attenuation of EAE symptoms
over 30 days of disease monitoring. These results correlated with lower percentage of proinflammatory interferon-
gamma and interleukin-17 producing cells and higher percentage of anti-inflammatory IL-4 producing
cells in spinal cord and spleen. Gut microbial composition were studied using amplicon(16S rRNA)-based
metagenomic analyses of fecal samples collected prior to the induction of EAE and MDSC-PGE2 therapy application,
and at the peak of the disease. The induction of EAE resulted in a decrease of microbiota diversity,
whereas the MDSC-PGE2 therapy preserved the diversity in EAE-induced animals. The induction of EAE
in control group associated with a higher relative abundance of Peptococcaceae, but the lower levels of Veillonellaceae
and different groups of Prevotellaceae, known to produce immunosuppressive short chain fatty
acid (SCFA), and Lactobacillus reuteri, known for its anti-inflammatory function. In contrast, there were no
changes in levels of these immunoregulatory taxa in EAE-animals treated with MDSC-PGE2 therapy. Also,
SCFA producing Ruminococcaceae, and Coriobacteriaceae, known to metabolize phytoestrogens to immunosuppressive
metabolites were more abundant in EAE-animals treated with MDSC-PGE2 therapy. Predicted
metabolic profiling obtained by PICRUSt2 revealed that pathways involved in biosynthesis of polyamines,
metabolites known to contribute to homeostasis of gastrointestinal mucosa, were enriched in MDSC-PGE2
treated animals. Considering these results, the modification of gut microbiota composition and function
could further increase efficacy of MDSC-PGE-2 based therapy of autoimmune diseases.
PB  - Novi Sad : Faculty of Sciences, Department of Biology and Ecology
C3  - Biologia Serbica
T1  - Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition
IS  - 1 (Special Edition)
SP  - 98
VL  - 43
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1875
ER  - 

@conference{
author = "Radojević, Dušan and Bekić, Marina and Gruden-Movsesijan, Alisa and Ilić, Nataša and Vasilev, Saša and Dinić, Miroslav and Golić, Nataša and Vučević, Dragana and Čolić, Miodrag and Tomić, Sergej and Đokić, Jelena",
year = "2021",
abstract = "The role of gut microbiota composition in efficacy of various immune-based therapies is increasingly recognized.
Thus, the aim of our study was to investigate if the efficacy of myeloid-derived suppressor cells
(MDSC)-Prostaglandin E2 (PGE2) therapy for multiple sclerosis (MS) correlates with gut microbiota composition
and function. MDSC generated from bone marrow cells in the presence of PGE2 were applied to spinal
cord homogenate/CFA-induced experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA)
rats, an animal model of MS. MDSC-PGE2 therapy resulted in a significant attenuation of EAE symptoms
over 30 days of disease monitoring. These results correlated with lower percentage of proinflammatory interferon-
gamma and interleukin-17 producing cells and higher percentage of anti-inflammatory IL-4 producing
cells in spinal cord and spleen. Gut microbial composition were studied using amplicon(16S rRNA)-based
metagenomic analyses of fecal samples collected prior to the induction of EAE and MDSC-PGE2 therapy application,
and at the peak of the disease. The induction of EAE resulted in a decrease of microbiota diversity,
whereas the MDSC-PGE2 therapy preserved the diversity in EAE-induced animals. The induction of EAE
in control group associated with a higher relative abundance of Peptococcaceae, but the lower levels of Veillonellaceae
and different groups of Prevotellaceae, known to produce immunosuppressive short chain fatty
acid (SCFA), and Lactobacillus reuteri, known for its anti-inflammatory function. In contrast, there were no
changes in levels of these immunoregulatory taxa in EAE-animals treated with MDSC-PGE2 therapy. Also,
SCFA producing Ruminococcaceae, and Coriobacteriaceae, known to metabolize phytoestrogens to immunosuppressive
metabolites were more abundant in EAE-animals treated with MDSC-PGE2 therapy. Predicted
metabolic profiling obtained by PICRUSt2 revealed that pathways involved in biosynthesis of polyamines,
metabolites known to contribute to homeostasis of gastrointestinal mucosa, were enriched in MDSC-PGE2
treated animals. Considering these results, the modification of gut microbiota composition and function
could further increase efficacy of MDSC-PGE-2 based therapy of autoimmune diseases.",
publisher = "Novi Sad : Faculty of Sciences, Department of Biology and Ecology",
journal = "Biologia Serbica",
title = "Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition",
number = "1 (Special Edition)",
pages = "98",
volume = "43",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1875"
}

Radojević, D., Bekić, M., Gruden-Movsesijan, A., Ilić, N., Vasilev, S., Dinić, M., Golić, N., Vučević, D., Čolić, M., Tomić, S.,& Đokić, J.. (2021). Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition. in Biologia Serbica
Novi Sad : Faculty of Sciences, Department of Biology and Ecology., 43(1 (Special Edition)), 98.
https://hdl.handle.net/21.15107/rcub_imagine_1875

Radojević D, Bekić M, Gruden-Movsesijan A, Ilić N, Vasilev S, Dinić M, Golić N, Vučević D, Čolić M, Tomić S, Đokić J. Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition. in Biologia Serbica. 2021;43(1 (Special Edition)):98.
https://hdl.handle.net/21.15107/rcub_imagine_1875 .

Radojević, Dušan, Bekić, Marina, Gruden-Movsesijan, Alisa, Ilić, Nataša, Vasilev, Saša, Dinić, Miroslav, Golić, Nataša, Vučević, Dragana, Čolić, Miodrag, Tomić, Sergej, Đokić, Jelena, "Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition" in Biologia Serbica, 43, no. 1 (Special Edition) (2021):98,
https://hdl.handle.net/21.15107/rcub_imagine_1875 .