TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Cepić, Aleksa
AU  - Bojić, Svetlana
AU  - Veljović, Katarina
AU  - Mihajlović, Sanja
AU  - Dedović, Neda
AU  - Jevtić, Bojan
AU  - Momcilović, Miljana
AU  - Lazarević, Milica
AU  - Mostarica-Stojković, Marija
AU  - Miljković, Đorđe
AU  - Golić, Nataša
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1272
AB  - Gut microbiota dysbiosis has been considered the essential element in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Antibiotics were administered orally to Dark Agouti (DA) rats early in their life with the aim of perturbing gut microbiota and investigating the effects of such intervention on the course of EAE. As a result, the diversity of the gut microbiota was reduced under the influence of antibiotics. Mainly, Firmicutes and Actinobacteria were replaced by Proteobacteria and Bacteroidetes, while decreased proportions of Clostridia and Bacilli classes were accompanied by an increase in Gamma-Proteobacteria in antibiotic-treated animals. Interestingly, a notable decrease in the Helicobacteraceae, Spirochaetaceae and Turicibacteriaceae was scored in antibiotic-treated groups. Also, levels of short chain fatty acids were reduced in the faeces of antibiotic-treated rats. Consequently, aggravation of EAE, paralleled with stronger immune response in lymph nodes draining the site of immunization, and increased inflammation within the CNS, were observed in antibiotic-treated DA rats. Thus, the alteration of gut microbiota leads to an escalation of CNS-directed autoimmunity in DA rats. The results of this study indicate that antibiotic use in early life may have subsequent unfavourable effects on the regulation of the immune system.
PB  - Nature Publishing Group, London
T2  - Scientific Reports
T1  - Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats
SP  - 918
VL  - 9
DO  - 10.1038/s41598-018-37505-7
ER  - 

@article{
author = "Stanisavljević, Suzana and Cepić, Aleksa and Bojić, Svetlana and Veljović, Katarina and Mihajlović, Sanja and Dedović, Neda and Jevtić, Bojan and Momcilović, Miljana and Lazarević, Milica and Mostarica-Stojković, Marija and Miljković, Đorđe and Golić, Nataša",
year = "2019",
abstract = "Gut microbiota dysbiosis has been considered the essential element in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Antibiotics were administered orally to Dark Agouti (DA) rats early in their life with the aim of perturbing gut microbiota and investigating the effects of such intervention on the course of EAE. As a result, the diversity of the gut microbiota was reduced under the influence of antibiotics. Mainly, Firmicutes and Actinobacteria were replaced by Proteobacteria and Bacteroidetes, while decreased proportions of Clostridia and Bacilli classes were accompanied by an increase in Gamma-Proteobacteria in antibiotic-treated animals. Interestingly, a notable decrease in the Helicobacteraceae, Spirochaetaceae and Turicibacteriaceae was scored in antibiotic-treated groups. Also, levels of short chain fatty acids were reduced in the faeces of antibiotic-treated rats. Consequently, aggravation of EAE, paralleled with stronger immune response in lymph nodes draining the site of immunization, and increased inflammation within the CNS, were observed in antibiotic-treated DA rats. Thus, the alteration of gut microbiota leads to an escalation of CNS-directed autoimmunity in DA rats. The results of this study indicate that antibiotic use in early life may have subsequent unfavourable effects on the regulation of the immune system.",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats",
pages = "918",
volume = "9",
doi = "10.1038/s41598-018-37505-7"
}

Stanisavljević, S., Cepić, A., Bojić, S., Veljović, K., Mihajlović, S., Dedović, N., Jevtić, B., Momcilović, M., Lazarević, M., Mostarica-Stojković, M., Miljković, Đ.,& Golić, N.. (2019). Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats. in Scientific Reports
Nature Publishing Group, London., 9, 918.
https://doi.org/10.1038/s41598-018-37505-7

Stanisavljević S, Cepić A, Bojić S, Veljović K, Mihajlović S, Dedović N, Jevtić B, Momcilović M, Lazarević M, Mostarica-Stojković M, Miljković Đ, Golić N. Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats. in Scientific Reports. 2019;9:918.
doi:10.1038/s41598-018-37505-7 .

Stanisavljević, Suzana, Cepić, Aleksa, Bojić, Svetlana, Veljović, Katarina, Mihajlović, Sanja, Dedović, Neda, Jevtić, Bojan, Momcilović, Miljana, Lazarević, Milica, Mostarica-Stojković, Marija, Miljković, Đorđe, Golić, Nataša, "Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats" in Scientific Reports, 9 (2019):918,
https://doi.org/10.1038/s41598-018-37505-7 . .

TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Dinić, Miroslav
AU  - Jevtić, Bojan
AU  - Dedović, Neda
AU  - Momcilović, Miljana
AU  - Đokić, Jelena
AU  - Golić, Nataša
AU  - Mostarica-Stojković, Marija
AU  - Miljković, Đorđe
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1179
AB  - Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-. and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Immunology
T1  - Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis
VL  - 9
DO  - 10.3389/fimmu.2018.00942
ER  - 

@article{
author = "Stanisavljević, Suzana and Dinić, Miroslav and Jevtić, Bojan and Dedović, Neda and Momcilović, Miljana and Đokić, Jelena and Golić, Nataša and Mostarica-Stojković, Marija and Miljković, Đorđe",
year = "2018",
abstract = "Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-. and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Immunology",
title = "Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis",
volume = "9",
doi = "10.3389/fimmu.2018.00942"
}

Stanisavljević, S., Dinić, M., Jevtić, B., Dedović, N., Momcilović, M., Đokić, J., Golić, N., Mostarica-Stojković, M.,& Miljković, Đ.. (2018). Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis. in Frontiers in Immunology
Frontiers Media Sa, Lausanne., 9.
https://doi.org/10.3389/fimmu.2018.00942

Stanisavljević S, Dinić M, Jevtić B, Dedović N, Momcilović M, Đokić J, Golić N, Mostarica-Stojković M, Miljković Đ. Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis. in Frontiers in Immunology. 2018;9.
doi:10.3389/fimmu.2018.00942 .

Stanisavljević, Suzana, Dinić, Miroslav, Jevtić, Bojan, Dedović, Neda, Momcilović, Miljana, Đokić, Jelena, Golić, Nataša, Mostarica-Stojković, Marija, Miljković, Đorđe, "Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis" in Frontiers in Immunology, 9 (2018),
https://doi.org/10.3389/fimmu.2018.00942 . .

TY  - JOUR
AU  - Jevtić, Bojan
AU  - Timotijević, Gordana
AU  - Stanisavljević, Suzana
AU  - Momcilović, Miljana
AU  - Mostarica-Stojković, Marija
AU  - Miljković, Djordje
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/821
AB  - MicroRNAs (miR) are small non-coding RNAs involved in the immune response regulation. miR-155 has been attributed a major pro-inflammatory role in the pathogenesis of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Here, a role of miR-155 in re-activation of encephalitogenic CD4(+) T cells was investigated. Dark Agouti rats were immunized with myelin basic protein (MBP) emulsified in complete Freund's adjuvant. CD4(+) T cells were purified from draining lymph node cells (DLNC) obtained in the inductive phase and from spinal cord immune cells (SCIC) isolated at the peak of EAE. CD4(+) T cells obtained from SCIC (i.e., in vivo re-activated cells) had markedly higher expression of miR-155 in comparison to those purified from DLNC (not re-activated). Likewise, in vitro re-activation of DLNC with MBP led to increase in miR-155 expression. Further, DLNC and DLNC CD4(+) T cells were transfected with an inhibitor of miR-155 during in vitro re-activation. As a result, expression of important CD4(+) T cell effector cytokines IFN-gamma and IL-17, but not of regulatory cytokines IL-10 and TGF-beta, was reduced. These results imply that miR-155 supports re-activation of encephalitogenic CD4+ T cells. Our results contribute to a view that miR-155 might be a valuable target in multiple sclerosis therapy.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2  - Biomedicine & Pharmacotherapy
T1  - Micro RNA-155 participates in re-activation of encephalitogenic T cells
EP  - 210
SP  - 206
VL  - 74
DO  - 10.1016/j.biopha.2015.08.011
ER  - 

@article{
author = "Jevtić, Bojan and Timotijević, Gordana and Stanisavljević, Suzana and Momcilović, Miljana and Mostarica-Stojković, Marija and Miljković, Djordje",
year = "2015",
abstract = "MicroRNAs (miR) are small non-coding RNAs involved in the immune response regulation. miR-155 has been attributed a major pro-inflammatory role in the pathogenesis of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Here, a role of miR-155 in re-activation of encephalitogenic CD4(+) T cells was investigated. Dark Agouti rats were immunized with myelin basic protein (MBP) emulsified in complete Freund's adjuvant. CD4(+) T cells were purified from draining lymph node cells (DLNC) obtained in the inductive phase and from spinal cord immune cells (SCIC) isolated at the peak of EAE. CD4(+) T cells obtained from SCIC (i.e., in vivo re-activated cells) had markedly higher expression of miR-155 in comparison to those purified from DLNC (not re-activated). Likewise, in vitro re-activation of DLNC with MBP led to increase in miR-155 expression. Further, DLNC and DLNC CD4(+) T cells were transfected with an inhibitor of miR-155 during in vitro re-activation. As a result, expression of important CD4(+) T cell effector cytokines IFN-gamma and IL-17, but not of regulatory cytokines IL-10 and TGF-beta, was reduced. These results imply that miR-155 supports re-activation of encephalitogenic CD4+ T cells. Our results contribute to a view that miR-155 might be a valuable target in multiple sclerosis therapy.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "Biomedicine & Pharmacotherapy",
title = "Micro RNA-155 participates in re-activation of encephalitogenic T cells",
pages = "210-206",
volume = "74",
doi = "10.1016/j.biopha.2015.08.011"
}

Jevtić, B., Timotijević, G., Stanisavljević, S., Momcilović, M., Mostarica-Stojković, M.,& Miljković, D.. (2015). Micro RNA-155 participates in re-activation of encephalitogenic T cells. in Biomedicine & Pharmacotherapy
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 74, 206-210.
https://doi.org/10.1016/j.biopha.2015.08.011

Jevtić B, Timotijević G, Stanisavljević S, Momcilović M, Mostarica-Stojković M, Miljković D. Micro RNA-155 participates in re-activation of encephalitogenic T cells. in Biomedicine & Pharmacotherapy. 2015;74:206-210.
doi:10.1016/j.biopha.2015.08.011 .

Jevtić, Bojan, Timotijević, Gordana, Stanisavljević, Suzana, Momcilović, Miljana, Mostarica-Stojković, Marija, Miljković, Djordje, "Micro RNA-155 participates in re-activation of encephalitogenic T cells" in Biomedicine & Pharmacotherapy, 74 (2015):206-210,
https://doi.org/10.1016/j.biopha.2015.08.011 . .