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Fecal microbial transplant for the treatment of pediatric inflammatory bowel disease

World Journal of Gastroenterology 2016年第47期22卷 10304-10315页

作者： Alice Yuxin Wang jelena popov Nikhil Pai Michael G DeG roote School of Medicine McM aster University Department of Pediatrics Division of Pediatric Gastroenterology Mc Master Children’s Hospital McM aster University Mc Master Integrative Neuroscience Discovery and Study Graduate Program Mc Master University

The role of fecal microbial transplant(FMT) in the treatment of pediatric gastrointestinal disease has become increasingly popular among pediatric practitioners, patients, and parents. The success of FMT for the treatment of recurrent Clostridium difficile infection(RCDI) has bolstered interest in its potential application to other disease states, such as inflammatory bowel disease(IBD). FMT has particular interest in pediatrics, given the concerns of patients and parents about rates of adverse events with existing therapeutic options, and the greater cumulative medication burden associated with childhoodonset disease. Published literature on the use of FMT in pediatrics is sparse. Only 45 pediatric patients treated for RCDI have been reported, and only 27 pediatric patients with pediatric IBD. The pediatric microbiome may uniquely respond to microbial-based therapies. This review will provide a comprehensive overview of fecal microbial transplant and its potential role in the treatment of pediatric inflammatory bowel disease. We will discuss the microbiome in pediatric inflammatory bowel disease, existing adult and pediatric literature on the use of FMT in IBD treatment, and pediatric FMT trials that are currently recruiting patients. This review will also discuss features of the microbiome that may be associated with host response in fecal transplant, and potential challenges and opportunities for the future of FMT in pediatric IBD treatment.

关键词： Inflammatory bowel disease Microbiome Microbiota fecal microbial transplant Pediatric Crohn’s disease Ulcerative colitis

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Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats

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Biomedical and Environmental Sciences 2019年第7期32卷 508-519页

作者： KULAS jelena NINKOV Marina TUCOVIC Dina popov Aleksandrov Aleksandra UKROPINA Mirela CAKIC MILOSEVIC Maja MUTIC jelena KATARANOVSKI Milena MIKROV Ivana Immunotoxicology group Department of Ecology Institute for Biological Research 'Sinisa Stankovic ' University of Belgrade 142 Bulevar despota Stefana Belgrade 11000 Serbia Institute of Zoology Faculty of Biology University of Belgrade 16 Studentskitrg Belgrade 11000 Serbia Innovation center of the Faculty of Chemistry University of Belgrade 12-16 Studentskitrg 11000 Belgrade Serbia Institute of Physiology and Biochemistry Faculty of Biology University of Belgrade 16 Studentskitrg Belgrade 11000 Serbia

Objective The aim of this study is to investigate the effects of oral cadmium(Cd) ingestion on the pulmonary immune response. Methods Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration(5 and 50 mg/L). Antioxidant enzyme defense(superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor(TNF) and interferon(IFN)-γ, as well as the activity of myeloperoxidase(MPO), nitric oxide(NO), and various cytokines [interleukin(IL)-1β, IL-6, IL-10, and IL-17] were investigated. Results Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. Conclusion The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.

关键词： Rats Oral cadmium administration Lungs Cytokine response

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Aryl Hydrocarbon Receptor is Involved in the Proinflammatory Cytokine Response to Cadmium

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Biomedical and Environmental Sciences 2021年第3期34卷 192-202页

作者： KULAS jelena TUCOVIC Dina ZELJKOVIC Milica popovIC Dusanka popov ALEKSANDROV Aleksandra KATARANOVSKI Milena MIRKOV Ivana Immunotoxicology Group Department of EcologyInstitute for Biological Research‘Sinisa Stankovic'-National Institute of Republic of SerbiaUniversity of Belgrade142 Bulevar despota StefanaBelgrade 11000Serbia

Objective To investigate involvement of the aryl hydrocarbon receptor(Ah R)in the immunomodulatory effects of cadmium(Cd).Methods The effect of Cd on Ah R activation(CYP1 A1 and CYP1 B1 m RNA expression)was examined in lung leukocytes of Cd-exposed rats(5 and 50 mg/L,30 d orally)and by in vitro leukocyte *** involvement of Ah R signaling in the effects of Cd on the interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)lung leukocyte response was investigated in vitro using the receptor antagonist *** Cd increased CYP1 B1(in vivo and in vitro)and CYP1 A1(in vitro)m RNA,indicating Ah R involvement in the action of *** response to Cd,lung leukocytes increased IL-6 and decreased TNF at the gene expression and protein levels,but decreased IL-1βproduction due to reduced *** Ah R antagonist CH-223191 abrogated the observed effects of Cd on the cytokine *** absence of Ah R reactivity and cytokine response to Cd of leukocytes from the lungs of a rat strain that is less sensitive to Cd toxicity coincided with a high Ah R repressor m RNA *** Ah R signaling is involved in the lung leukocyte proinflammatory cytokine response to *** relevance of the Ah R to the cytokine response to Cd provides new insight into the mechanisms of Cd immunotoxicity.

关键词： Cadmium Lung leukocytes Aryl hydrocarbon receptor Cytokine(IL-6,TNF,IL-1β)response

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Physiological strategies in wild rodents:immune defenses of commensal rats

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Integrative Zoology 2024年第3期19卷 350-370页

作者： Ivana MIRKOV Dina TUCOVIC jelena KULAS Anastasija MALESEVIC Dragan KATARANOVSKI Milena KATARANOVSKI Aleksandra popov ALEKSANDROV Immunotoxicology Group Department of EcologyInstitute for Biological Research“Sinisa Stankovic”—National Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia

The importance of issues associated with urban/commensal rats and mice(property damage,management costs,and health risks)press upon research on these *** the demography of commensal rodents is mostly studied,the need for understanding factors influencing their natural morbidity/mortality is also *** this respect,more attention is expected to be paid to immunity,the physiological mechanism of defense against host survival threats(pathogens,parasites,diseases).Commensal rats and mice carry numerous pathogens that evoke diverse immune *** state of immunity in commensal house mice is studied in great detail,owing to the use of laboratory strains in biomedical *** commensal rats are,compared to mice,carriers of more zoonotic agents,rats’immunity is studied mainly in that *** of these zoonotic agents cause chronic,asymptomatic infections,which justified studies of immunological mechanisms of pathogen tolerance versus clearance regulation in *** of some infections in specific tissues/organs pressed upon analysis of local/regional immune responses and/or immunopathology.A survey of immunological activity/responses in commensal rats is given in this review,with mention of existing data in commensal *** should throw some light on the factors relevant to their morbidity and lifespan,supplementing the knowledge of commensal rodent ecology.

关键词： commensal rats and mice immunopathology infection inflammation tolerance

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Oral Cadmium Intake Enhances Contact Allergen-induced Skin Reaction in Rats

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Biomedical and Environmental Sciences 2022年第11期35卷 1038-1050页

作者： Dina Tucovic jelena Kulas Ivana Mirkov Dusanka popovic Lidija Zolotarevski Marta Despotovic Milena Kataranovski Aleksandra popov Aleksandrov Immunotoxicology Group Department of EcologyInstitute for Biological Research"Sinisa Stankovic"-National Institute of Republic of SerbiaUniversity of Belgrade142 Bulevar despota Stefana11060 BelgradeSerbia Medical College of Applied Sciences 254 Cara Dusana11080 BelgradeSerbia Centre of Research Excellence in Nutrition and Metabolism Institute for Medical ResearchUniversity of Belgrade11 Tadeusa Koscuska 111000 BelgradeSerbia

Objective The effect of oral cadmium(Cd)intake to influence contact skin allergies was examined,since it is known that Cd is a heavy metal that affects many tissues,including the skin,in which it disturbs homeostasis,thus resulting in inflammation and *** Male rats were evoked with experimental contact hypersensitivity reaction(CHS)to hapten dinitrochlorobenzene(DNCB),after prolonged(30 day)oral exposure to an environmentally relevant Cd dose(5 ppm).The ear cell population was analyzed with flow *** production by ear skin cells and the activity of skin-draining lymph node(DLN)cells were measured using enzyme-linked immunosorbent assay(ELISA).Results Orally acquired Cd(5 ppm)increased CHS intensity only in Dark Agouti(DA)rats by affecting inflammatory responses in both the sensitization(an increase of IFN-γ and IL-17 cytokine production)and challenge(an increase of CD8^(+)and CD4^(+)cell number and TNF,IFN-γ and IL-17 cytokine production)*** increased CHS reaction was seen in Albino Oxford(AO)rats only at a high Cd dose(50 ppm),during the challenge phase(an increase of CD8^(+)and CD4^(+)cell number and TNF,IFN-γ and IL-17 cytokine production).Conclusion These novel data indicate that oral Cd intensifies the skin response to sensitizing chemicals such as DNCB.

关键词： Cadmium(Cd) Contact hypersensitivity reaction(CHS) Dinitrochlorobenzene(DNCB)

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Gender Differences in Pulmonary Inflammation Following Systemic Cadmium Administration in Rats

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Biomedical and Environmental Sciences 2010年第4期23卷 293-299页

作者： jelena STOSIC IVANA MIRKOV SANDRA BELIJ MIROSLAV NIKOLIC ALEKSANDRA popov DRAGAN KATARANOVSKI MILENA KATARANOVSKI Department of Ecology Institute for Biological Research "Sinisa Stankovic" Institute for Multidisciplinary Research University of Belgrade Institute of Zoology Faculty of BiologyUniversity of Belgrade Institute of Physiology and Biochemistry Faculty of BiologyUniversity of Belgrade

Objective To examine the presence of gender differences in pulmonary inflammation evoked by acute systemic cadmium administration in rats. Methods Presence of basic indicators of lung inflammation （inflammatory cytokine lung content, leukocyte infiltration and activity of cells recovered from lungs by enzyme digestion） was analyzed and compared in animals of the two sexes. Results Intraperitoneal administration of cadmium （1.0 mg/kg） resulted in higher cadmium content in lungs of female rats. Higher tumor necrosis factor （TNF） content was noted in lung homogenates of male rats, while interleukin-6 （IL-6） content was slightly, but signifaicantly greater in lungs of female rats. Increased leukocyte infiltration was observed in lungs of male rats, mainly due to neutrophils. Increased responsiveness to phorbol myristate acetate （PMA） stimulation was noted in cells recovered from lungs of male rats. Rise in intracellular content of myeloperoxidase （MPO） was noted in lung cells from cadmium-treated rats of both sexes, but higher in cells from male rats. Conclusion Presented data documented a more intense pulmonary inflammatory response to systemic cadmium administration in males, with higher IL-6 levels in lungs of female individuals. These sex differences in proinflamatory activity of cadmium in lungs should be taken into consideration in studying the remote toxicity of this heavy metal.

关键词： Rats Sex Intraperitoneal cadmium Pulmonary inflammation

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Pulmonary Immune Responses to Aspergillus Fumigatus in Rats

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Biomedical and Environmental Sciences 2014年第9期27卷 684-694页

作者： MIRKOV Ivana EL-MUZGHI Amal Atia Mhfuod DJOKIC jelena NINKOV Marina popov ALEKSANDROV Aleksandra GLAMOCLIJA Jasmina KATARANOVSKI Milena Department of Ecology Institute for Biological Research ‘Sinisa Stankovic'University of Belgrade Department of Plant Physiology (Mycology Lab) Institute for Biological Research ‘Sinisa Stankovic'University of Belgrade Institute of Physiology and Biochemistry Faculty of BiologyUniversity of Belgrade

Objective To evaluate immunologic mechanisms underlying Aspergillus fumigatus pulmonary infections in immunocompetent Dark Agouti （DA） and Albino Oxford （AO） rats recognized as being susceptible to some inflammatory diseases in different manners. Methods Lung fungal burden （quantitative colony forming units, CFU, assay）, leukocyte infiltration （histology, cell composition） and their function （phagocytosis, oxidative activity, CDllb adhesion molecule expression） and cytokine interferon-y （IFN-y） and interleukin-17 and -4 （IL-17 and IL-4） lung content were evaluated following infection （intratracheally, lxl07 conidia）. Results Slower reduction of fungal burden was observed in AO rats in comparison with that in DA rats, which was coincided with less intense histologically evident lung cell infiltration and leukocyte recovery as well as lower level of most of the their activities including intracellular myeloperoxidase activity, the capacity of nitroblue tetrazolium salt reduction and CDllb adhesion molecule expression （except for phagocytosis of conidia） in these rats. Differential patterns of changes in proinflammatory cytokine levels （unchanged levels of IFN-v and transient increase of IL-17 in AO rats vs continuous increase of both cytokines in DA rats） and unchanged levels of IL-4 were observed. Conclusion Genetically-based differences in the pattern of antifungal lung leukocyte activities and cytokine milieu, associated with differential efficiency of fungal elimination might be useful in the future use of rat models in studies of pulmonary aspergillosis.

关键词： A. fumigatus Rats Lung immune responses

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