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1
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Chen X, Li Q, Xie J, Nie S. Immunomodulatory Effects of Probiotic-Derived Extracellular Vesicles: Opportunities and Challenges. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:19259-19273. [PMID: 39177683 DOI: 10.1021/acs.jafc.4c04223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/24/2024]
Abstract
Probiotics are known to modulate host immune responses in the course of many diseases. Recently, bacterial extracellular vesicles (EVs), which contain bioactive proteins, lipids, nucleic acids, and metabolites released by bacteria, have been identified as potentially important mediators of bacteria-bacterium and bacteria-host interactions. With the deepening of research, it has been found that probiotic-derived EVs play a significant role in regulating host immune function and, thus, exerting health-promoting effects. Nevertheless, current research is in its early stages, and there remains a long way to go to bridge the gap between basic research and clinical practice. In this review, we describe the fundamental aspects of probiotic-derived EVs, including their biogenesis, cargo sorting mechanism, and transport capabilities. We further discussed the potential mechanisms of probiotic-derived EVs in regulating the host's gut microbiota and immune responses. Finally, we speculate about the potential of probiotic-derived EVs as new postbiotics for applications in functional food, disease treatment substitutes, and immune regulatory adjuvants.
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Affiliation(s)
- Xinyang Chen
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China
| | - Qiqiong Li
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China
| | - Junhua Xie
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China
| | - Shaoping Nie
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China
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2
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Rückle X, Rühle J, Judd L, Hebel J, Dietz S, Poets CF, Gille C, Köstlin-Gille N. Different probiotic strains alter human cord blood monocyte responses. Pediatr Res 2022:10.1038/s41390-022-02400-5. [PMID: 36476746 DOI: 10.1038/s41390-022-02400-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 10/24/2022] [Accepted: 11/09/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Probiotics have a protective effect on various diseases. In neonatology, they are predominantly used to prevent necrotising enterocolitis (NEC), a severe inflammatory disease of the neonatal intestine. The mechanisms by which probiotics act are diverse; little is known about their direct effect on neonatal immune cells. METHODS In this study, we investigated the effect of probiotics on the functions of neonatal monocytes in an in vitro model using three different strains (Lactobacillus rhamnosus (LR), Lactobacillus acidophilus (LA) and Bifidobacterium bifidum (BB)) and mononuclear cells isolated from cord blood. RESULTS We show that stimulation with LR induces proinflammatory effects in neonatal monocytes, such as increased expression of surface molecules involved in monocyte activation, increased production of pro-inflammatory and regulatory cytokines and increased production of reactive oxygen species (ROS). Similar effects were observed when monocytes were stimulated simultaneously with LPS. Stimulation with LA and BB alone or in combination also induced cytokine production in monocytes, with BB showing the least effects. CONCLUSIONS Our results suggest that probiotics increase the defence functions of neonatal monocytes and thus possibly favourably influence the newborn's ability to fight infections. IMPACT Probiotics induce a proinflammatory response in neonatal monocytes in vitro. This is a previously unknown mechanism of how probiotics modulate the immune response of newborns. Probiotic application to neonates may increase their ability to fight off infections.
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Affiliation(s)
- Xenia Rückle
- Department of Neonatology, Tübingen University Children's Hospital, Tübingen, Germany
| | - Jessica Rühle
- Department of Neonatology, Tübingen University Children's Hospital, Tübingen, Germany
| | - Leonie Judd
- Department of Neonatology, Tübingen University Children's Hospital, Tübingen, Germany
| | - Janine Hebel
- Department of Neonatology, Tübingen University Children's Hospital, Tübingen, Germany
| | - Stefanie Dietz
- Department of Neonatology, Tübingen University Children's Hospital, Tübingen, Germany.,Department of Neonatology, Heidelberg University Children's Hospital, Heidelberg, Germany
| | - Christian F Poets
- Department of Neonatology, Tübingen University Children's Hospital, Tübingen, Germany
| | - Christian Gille
- Department of Neonatology, Heidelberg University Children's Hospital, Heidelberg, Germany
| | - Natascha Köstlin-Gille
- Department of Neonatology, Tübingen University Children's Hospital, Tübingen, Germany. .,Department of Neonatology, Heidelberg University Children's Hospital, Heidelberg, Germany.
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3
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Effect of cultured white soft cheese on the histopathological changes in the kidneys and liver of albino rats. Sci Rep 2022; 12:2564. [PMID: 35169197 PMCID: PMC8847355 DOI: 10.1038/s41598-022-06522-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 02/01/2022] [Indexed: 11/29/2022] Open
Abstract
Three different types of lactic acid bacteria (Lactobacillus helveticus, Lactobacillus rhamnosus and Streptococcus thermophilus S3855) were used to manufacture white soft cheese. The resultant white soft cheeses were pickled for 28 days at refrigerator temperatures and were fed to the experimental rats. The chemical and microbiological analyses of white soft cheese were conducted at different storage periods (fresh, 7 days, 14 days, 21 days, and 28 days). The pH values and protein content of white soft cheese gradually decreased during the storage peroid. Conversely, the moisture content, titratable acidity, and fat/DM % of white soft cheese were found to increase with of the increase in pickling periods of up to 28 days. Microbiologically, the total viable count of bacteria in the control samples was lower than that in the other treatments. Furthermore, the treatments containing the L. helveticus and L. rhamnosus strains had the highest lactoacilli counts whereas the treatment containing the S. thermophilus strain had the highest streptococci counts. Twenty-five male Albino rats were used for experiemntal technique. Rats were fed with 70% basal diet with addition of 30% white soft cheese. Several pathological findings were present in all experimental groups apart from the control rats, and the kidney samples exhibited renal vascular congestion especially in the cortical area. The changes of the glomeruli comprise atrophy, distortion, hypocellularity of the glomerular tuft, and focal lymphoid cell reactions. The renal tubular epithelium showed a series of degenerative changes ranging up to necrosis. The liver samples showed variable hepatic injury in the form of thickening in the Glisson capsule, as well as dissociation and disorganization of hepatic cords. Hepatocellular vacuolar degeneration, presence of focal areas of nodular hyperplasia, the hyperplastic cells mixed with lymphocytic infiltration, congestion in the portal vein, periportal fibrosis and edema with the presence of newly formed nonfunctional bile ductulus. Based on the histopathology scores, the severity of renal and hepatic changes was significantly increased (P ≤ 0.05) in all of the experimental groups compared with the control group. Generally, the chemical composition, microbiological analysis and vital organs were significantly affected by using cultured white soft cheese.
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Engevik MA, Ruan W, Esparza M, Fultz R, Shi Z, Engevik KA, Engevik AC, Ihekweazu FD, Visuthranukul C, Venable S, Schady DA, Versalovic J. Immunomodulation of dendritic cells by Lactobacillus reuteri surface components and metabolites. Physiol Rep 2021; 9:e14719. [PMID: 33463911 PMCID: PMC7814497 DOI: 10.14814/phy2.14719] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 12/16/2020] [Accepted: 12/17/2020] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Lactic acid bacteria are commensal members of the gut microbiota and are postulated to promote host health. Secreted factors and cell surface components from Lactobacillus species have been shown to modulate the host immune system. However, the precise role of L. reuteri secreted factors and surface proteins in influencing dendritic cells (DCs) remains uncharacterized. HYPOTHESIS We hypothesize that L. reuteri secreted factors will promote DC maturation, skewing cells toward an anti-inflammatory phenotype. In acute colitis, we speculate that L. reuteri promotes IL-10 and dampens pro-inflammatory cytokine production, thereby improving colitis. METHODS & RESULTS Mouse bone marrow-derived DCs were differentiated into immature dendritic cells (iDCs) via IL-4 and GM-CSF stimulation. iDCs exposed to L. reuteri secreted factors or UV-irradiated bacteria exhibited greater expression of DC maturation markers CD83 and CD86 by flow cytometry. Additionally, L. reuteri stimulated DCs exhibited phenotypic maturation as denoted by cytokine production, including anti-inflammatory IL-10. Using mouse colonic organoids, we found that the microinjection of L. reuteri secreted metabolites and UV-irradiated bacteria was able to promote IL-10 production by DCs, indicating potential epithelial-immune cross-talk. In a TNBS-model of acute colitis, L. reuteri administration significantly improved histological scoring, colonic cytokine mRNA, serum cytokines, and bolstered IL-10 production. CONCLUSIONS Overall these data demonstrate that both L. reuteri secreted factors and its bacterial components are able to promote DC maturation. This work points to the specific role of L. reuteri in modulating intestinal DCs. NEW & NOTEWORTHY Lactobacillus reuteri colonizes the mammalian gastrointestinal tract and exerts beneficial effects on host health. However, the mechanisms behind these effects have not been fully explored. In this article, we identified that L. reuteri ATTC PTA 6475 metabolites and surface components promote dendritic cell maturation and IL-10 production. In acute colitis, we also demonstrate that L. reuteri can promote IL-10 and suppress inflammation. These findings may represent a crucial mechanism for maintaining intestinal immune homeostasis.
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Affiliation(s)
- Melinda A Engevik
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.,Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Wenly Ruan
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.,Section of Gastroenterology, Hepatology, and Nutrition, Texas Children's Hospital, Houston, TX, USA
| | - Magdalena Esparza
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.,Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Robert Fultz
- Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX, USA
| | - Zhongcheng Shi
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.,Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Kristen A Engevik
- Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Amy C Engevik
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Faith D Ihekweazu
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.,Section of Gastroenterology, Hepatology, and Nutrition, Texas Children's Hospital, Houston, TX, USA
| | - Chonnikant Visuthranukul
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.,Pediatric Nutrition Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Susan Venable
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.,Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Deborah A Schady
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.,Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - James Versalovic
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.,Department of Pathology, Texas Children's Hospital, Houston, TX, USA
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Shukla R, Ruwali M, Sharath Pawar N, Flora SJS. Role of Probiotics in Rheumatoid Arthritis. PROBIOTIC RESEARCH IN THERAPEUTICS 2021:273-294. [DOI: 10.1007/978-981-15-8214-1_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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6
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Sotoudegan F, Daniali M, Hassani S, Nikfar S, Abdollahi M. Reappraisal of probiotics’ safety in human. Food Chem Toxicol 2019; 129:22-29. [DOI: 10.1016/j.fct.2019.04.032] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 04/16/2019] [Accepted: 04/17/2019] [Indexed: 02/07/2023]
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7
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Effect of whey-pearl millet-barley based probiotic beverage on Shigella-induced pathogenicity in murine model. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.01.049] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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Roh YS, Cho A, Cha YS, Oh SH, Lim CW, Kim B. Lactobacillus Aggravate Bile Duct Ligation-Induced Liver Inflammation and Fibrosis in Mice. Toxicol Res 2018; 34:241-247. [PMID: 30057698 PMCID: PMC6057294 DOI: 10.5487/tr.2018.34.3.241] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 03/08/2018] [Accepted: 05/31/2018] [Indexed: 01/07/2023] Open
Abstract
Lactobacillus (LAB) have been reported to exert both harmful and beneficial effects on human and animal health. Recently, it has been reported that dysbiosis and bacterial translocation contribute to liver fibrosis. However, the role of Gram-positive LAB in the situation of chronic liver diseases has not been yet elucidated. Liver injury was induced by bile duct ligation (BDL) in LAB or control-administered mice. Liver fibrosis was enhanced in LAB-administered mice compared with control-treated mice as demonstrated by quantification of Sirius-red positive area, hydroxyproline contents and fibrosis-related genes (Col1α1, Acta2, Timp1, Tgfb1). Moreover, LAB-administered mice were more susceptible to BDL-induced liver injury as shown by increased ALT and AST level of LAB group compared with control group at 5 days post BDL. Consistent with serum level, inflammatory cytokines (TNF-α, IL-6 and IL-1β) were also significantly increased in LAB-treated mice. Of note, LAB-treated liver showed increased lipoteichoic acid (LTA) expression compared with control-treated liver, indicating that LAB-derived LTA may translocate from intestine to liver via portal vein. Indeed, responsible receptor or inflammatory factor (PAFR and iNOS) for LTA were upregulated in LAB-administered group. The present findings demonstrate that administration of LAB increases LTA translocation to liver and induces profibrogenic inflammatory milieu, leading to aggravation of liver fibrosis. The current study provides new cautious information of LAB for liver fibrosis patients to prevent the detrimental effect of LAB supplements.
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Affiliation(s)
- Yoon Seok Roh
- Department of Pharmacy, Chungbuk National University, College of Pharmacy and Medical Research Center, Cheongju, Korea
| | - Ara Cho
- Biosafety Research Institute and College of Veterinary Medicine (BK21 Plus Program), Chonbuk National University, Iksan, Korea
| | - Youn-Soo Cha
- Department of Food Science and Human Nutrition, Fermented Food Research Center, Chonbuk National University, Jeonju, Korea
| | - Suk-Heung Oh
- Department of Food & Biotechnology, Woosuk University, Jeonju, Korea
| | - Chae Woong Lim
- Biosafety Research Institute and College of Veterinary Medicine (BK21 Plus Program), Chonbuk National University, Iksan, Korea
| | - Bumseok Kim
- Biosafety Research Institute and College of Veterinary Medicine (BK21 Plus Program), Chonbuk National University, Iksan, Korea
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9
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Consonni A, Cordiglieri C, Rinaldi E, Marolda R, Ravanelli I, Guidesi E, Elli M, Mantegazza R, Baggi F. Administration of bifidobacterium and lactobacillus strains modulates experimental myasthenia gravis and experimental encephalomyelitis in Lewis rats. Oncotarget 2018; 9:22269-22287. [PMID: 29854277 PMCID: PMC5976463 DOI: 10.18632/oncotarget.25170] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Accepted: 04/03/2018] [Indexed: 12/15/2022] Open
Abstract
Probiotics beneficial effects on the host are associated with regulation of the intestinal microbial homeostasis and with modulation of inflammatory immune responses in the gut and in periphery. In this study, we investigated the clinical efficacy of two lactobacillus and two bifidobacterium probiotic strains in experimental autoimmune myasthenia gravis (EAMG) and experimental autoimmune encephalomyelitis (EAE) models, induced in Lewis rats. Treatment with probiotics led to less severe disease manifestation in both models; ex vivo analyses showed preservation of neuromuscular junction in EAMG and myelin content in EAE spinal cord. Immunoregulatory transcripts were found differentially expressed in gut associated lymphoid tissue and in peripheral immunocompetent organs. Feeding EAMG animals with probiotics resulted in increased levels of Transforming Growth Factor-β (TGFβ) in serum, and increased percentages of regulatory T cells (Treg) in peripheral blood leukocyte. Exposure of immature dendritic cells to probiotics induced their maturation toward an immunomodulatory phenotype, and secretion of TGFβ. Our data showed that bifidobacteria and lactobacilli treatment effectively modulates disease symptoms in EAMG and EAE models, and support further investigations to evaluate their use in autoimmune diseases.
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Affiliation(s)
- Alessandra Consonni
- Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute 'Carlo Besta', Milan, Italy
| | - Chiara Cordiglieri
- Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute 'Carlo Besta', Milan, Italy
| | - Elena Rinaldi
- Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute 'Carlo Besta', Milan, Italy
| | - Roberta Marolda
- Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute 'Carlo Besta', Milan, Italy
| | - Ilaria Ravanelli
- Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute 'Carlo Besta', Milan, Italy
| | - Elena Guidesi
- AAT-Advanced Analytical Technologies, Fiorenzuola d'Arda, Piacenza, Italy
| | - Marina Elli
- AAT-Advanced Analytical Technologies, Fiorenzuola d'Arda, Piacenza, Italy
| | - Renato Mantegazza
- Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute 'Carlo Besta', Milan, Italy
| | - Fulvio Baggi
- Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute 'Carlo Besta', Milan, Italy
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10
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Ge A, Fu F, Wang X. The enhancing effect of Klebsiella pneumoniae lysate on cellular immunity. EUR J INFLAMM 2018. [DOI: 10.1177/2058739218776476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Cellular immunity plays important roles in clearing intracellular pathogens or tumor cells. It is of significance to develop an adjuvant able to efficaciously induce cellular immunity, but such an approved adjuvant is not currently available. Klebsiella pneumoniae ( K. pneumoniae) possesses lipopolysaccharide and capsular polysaccharide, both of which have been demonstrated to be able to induce humoral immunity. In this study, we investigated the effect of K. pneumoniae on epidermal cellular immunity, in vitro. The effects of K. pneumoniae on the maturation of Langerhans cells (LCs), the capacity to induce T-cell proliferation, and the secretion of interferon gamma (IFN-γ) by T cells were examined. The results showed that K. pneumoniae induced significant upregulation of CD86 and human leukocyte antigen-deterodimer (HLA-DR) levels on LCs, but not CD40 and CD80. K. pneumoniae-loaded LCs induced significant CD4+ and CD8+ T-cell proliferation. Significant increases in extracellular IFN-γ secretion by CD4+ and CD8+ T cells stimulated with K. pneumoniae-pulsed LCs using enzyme-linked immunospot assay (ELISPOT) were demonstrated, while only a part of the subjects showed increases in intracellular secretion of IFN-γ using intracellular staining assay. In sum, K. pneumoniae has the potential to enhance epidermal cellular immunity and may act as a potential adjuvant in intradermal vaccines designed to enhance cellular immunity.
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Affiliation(s)
- Anxing Ge
- Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China
- Research Center of Biomedical Technology, Jiangsu Vocational College of Medicine, Yancheng, China
| | - Fangjie Fu
- Third Department of Clinical Medicine, China Medical University, Shenyang, China
| | - Xuelian Wang
- Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China
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11
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Wang P, Tao JH, Pan HF. Probiotic bacteria: a viable adjuvant therapy for relieving symptoms of rheumatoid arthritis. Inflammopharmacology 2016; 24:189-196. [PMID: 27581587 DOI: 10.1007/s10787-016-0277-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 08/23/2016] [Indexed: 01/05/2023]
Abstract
The burgeoning use of probiotics has proliferated during the past two decades. However, the effect of probiotic administration for either the prevention or treatment of rheumatoid arthritis (RA) has been investigated in a limited number of studies. Randomized controlled clinical trials have provided evidences that specific probiotics supplementation exhibit anti-inflammatory effects, help to increase daily activities and alleviate symptoms in patients with RA. Therefore, using probiotic bacteria as an adjuvant therapy may be considered as a promising treatment option for RA. This review summarizes the available data about the therapeutic and preventive effect of probiotics in RA, together with probiotic supplement as a possible therapy in clinical treatment.
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Affiliation(s)
- Peng Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China
- Anhui Provincial Laboratory of Population Health & Major Disease Screening and Diagnosis, Hefei, Anhui, China
| | - Jin-Hui Tao
- Department of Rheumatology, Anhui Provincial Hospital, Hefei, Anhui, China
| | - Hai-Feng Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.
- Anhui Provincial Laboratory of Population Health & Major Disease Screening and Diagnosis, Hefei, Anhui, China.
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12
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Immunoregulatory effects triggered by immunobiotic Lactobacillus jensenii TL2937 strain involve efficient phagocytosis in porcine antigen presenting cells. BMC Immunol 2016; 17:21. [PMID: 27342653 PMCID: PMC4921007 DOI: 10.1186/s12865-016-0160-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 06/17/2016] [Indexed: 11/21/2022] Open
Abstract
Background Immunobiotic Lactobacillus jensenii TL2937 modulates porcine mononuclear phagocytes from Peyer’s patches (PPMPs) and induces a differential production of pro- and anti-inflammatory cytokines in response to Toll-like receptor (TLR)-4 activation. In view of the important role played by phagocytosis in the activation of antigen presenting cells (APCs), the aim of the present work was to examine the interaction of TL2937 with porcine PPMPs focusing on phagocytosis. In addition, this study aimed to investigate whether the effects of L. jensenii TL2937 in porcine blood monocyte-derived dendritic cells (MoDCs) are similar to those found in PPMPs considering that MoDCs do not recapitulate all functions of mucosal APCs. Results Studies showed a high ability of porcine CD172a+ PPMPs to phagocytose L. jensenii TL2937. Interestingly, our results also revealed a reduced capacity of the non-immunomodulatory L. plantarum TL2766 to be phagocytosed by those immune cells. Phagocytosis of L. jensenii TL2937 by porcine PPMPs was partially dependent on TLR2. In addition, we demonstrated that TL2937 strain was able to improve the expression of IL-1β, IL-12 and IL-10 in immature MoDCs resembling the effect of this immunobiotic bacterium on PPMPs. Moreover, similarly to PPMPs those immunomodulatory effects were related to the higher capacity of TL2937 to be phagocytosed by immature MoDCs. Conclusions Microbial recognition in APCs could be effectively mediated through ligand-receptor interactions that then mediate phagocytosis and signaling. For the immunobiotic strain TL2937, TLR2 has a partial role for its interaction with porcine APCs and it is necessary to investigate the role of other receptors. A challenge for future research will be advance in the full understanding of the molecular interactions of immunobiotic L. jensenii TL2937 with porcine APCs that will be crucial for the successful development of functional feeds for the porcine host. This study is a step in that direction.
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13
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Parker D, Ahn D, Cohen T, Prince A. Innate Immune Signaling Activated by MDR Bacteria in the Airway. Physiol Rev 2016; 96:19-53. [PMID: 26582515 DOI: 10.1152/physrev.00009.2015] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation.
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Affiliation(s)
- Dane Parker
- Departments of Pediatrics and Pharmacology, Columbia University, New York, New York
| | - Danielle Ahn
- Departments of Pediatrics and Pharmacology, Columbia University, New York, New York
| | - Taylor Cohen
- Departments of Pediatrics and Pharmacology, Columbia University, New York, New York
| | - Alice Prince
- Departments of Pediatrics and Pharmacology, Columbia University, New York, New York
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14
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Abstract
Probiotics have been used safely for years. Safety outcomes are inconsistently reported in published clinical trials. In 2011, a report released by the Agency for Healthcare Research and Quality concluded that, although the existing probiotic clinical trials reveal no evidence of increased risk, "the current literature is not well equipped to answer questions on the safety of probiotics in intervention studies with confidence." Critics point out that the preponderance of evidence, including the long history of safe probiotic use as well as data from clinical trials, and animal and in vitro studies all support the assumption that probiotics are generally safe for most populations. Theoretical risks have been described in case reports, clinical trial results and experimental models, include systemic infections, deleterious metabolic activities, excessive immune stimulation in susceptible individuals, gene transfer and gastrointestinal side effects. More research is needed to properly describe the incidence and severity of adverse events related to probiotics.
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Affiliation(s)
- Shira Doron
- Division of Infectious Diseases, Tufts Medical Center, Boston, Massachusetts
| | - David R Snydman
- Division of Infectious Diseases, Tufts Medical Center, Boston, Massachusetts
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15
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T cell polarizing properties of probiotic bacteria. Immunol Lett 2015; 168:337-42. [DOI: 10.1016/j.imlet.2015.11.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Revised: 10/29/2015] [Accepted: 11/04/2015] [Indexed: 12/30/2022]
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16
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Lactic acid bacteria strains exert immunostimulatory effect on H. pylori-induced dendritic cells. J Immunol Res 2015; 2015:106743. [PMID: 25759836 PMCID: PMC4352478 DOI: 10.1155/2015/106743] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2014] [Revised: 09/11/2014] [Accepted: 09/15/2014] [Indexed: 01/15/2023] Open
Abstract
The aim of this study was to find out if selected lactic acid bacteria (LAB) strains (antagonistic or nonantagonistic against H. pylori in vitro) would differ in their abilities to modulate the DCs maturation profiles reflected by their phenotype and cytokine expression patterns. Methods. Monocyte-derived DCs maturation was elicited by their direct exposure to the LAB strains of L. rhamnosus 900 or L. paracasei 915 (antagonistic and nonantagonistic to H. pylori, resp.), in the presence or absence of H. pylori strain cagA+. The DCs maturation profile was assessed on the basis of surface markers expression and cytokines production. Results. We observed that the LAB strains and the mixtures of LAB with H. pylori are able to induce mature DCs. At the same time, the L. paracasei 915 leads to high IL-10/IL-12p70 cytokine ratio, in contrast to L. rhamnosus 900. Conclusions. This study showed that the analyzed lactobacilli strains are more potent stimulators of DC maturation than H. pylori. Interestingly from the two chosen LAB strains the antagonistic to H. pylori-L. rhamnosus strain 900 has more proinflammatory and probably antibactericidal properties.
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Abstract
Probiotic organisms are claimed to offer several functional properties including stimulation of immune system. This review is presented to provide detailed informations about how probiotics stimulate our immune system. Lactobacillus rhamnosus GG, Lactobacillus casei Shirota, Bifidobacterium animalis Bb-12, Lactobacillus johnsonii La1, Bifidobacterium lactis DR10, and Saccharomyces cerevisiae boulardii are the most investigated probiotic cultures for their immunomodulation properties. Probiotics can enhance nonspecific cellular immune response characterized by activation of macrophages, natural killer (NK) cells, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in strain-specific and dose-dependent manner. Mixture and type (gram-positive and gram-negative) of probiotic organisms may induce different cytokine responses. Supplementation of probiotic organisms in infancy could help prevent immune-mediated diseases in childhood, whereas their intervention in pregnancy could affect fetal immune parameters, such as cord blood interferon (IFN)-γ levels, transforming growth factor (TGF)-β1 levels, and breast milk immunoglobulin (Ig)A. Probiotics that can be delivered via fermented milk or yogurt could improve the gut mucosal immune system by increasing the number of IgA(+) cells and cytokine-producing cells in the effector site of the intestine.
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Affiliation(s)
- Rabia Ashraf
- a Faculty of Health Engineering and Science, School of Biomedical and Health Sciences , Victoria University , Werribee Campus, P.O. Box 14428 , Melbourne , Victoria , 8001 , Australia
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18
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Villena J, Kitazawa H. Modulation of Intestinal TLR4-Inflammatory Signaling Pathways by Probiotic Microorganisms: Lessons Learned from Lactobacillus jensenii TL2937. Front Immunol 2014; 4:512. [PMID: 24459463 PMCID: PMC3890654 DOI: 10.3389/fimmu.2013.00512] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Accepted: 12/26/2013] [Indexed: 12/21/2022] Open
Abstract
The intestinal mucosa plays a critical role in the host’s interactions with innocuous commensal microbiota and invading pathogenic microorganisms. Intestinal epithelial cells (IECs) and gut associated immune cells recognize the bacterial components via pattern-recognition receptors (PRRs) and are responsible for maintaining tolerance to the large communities of resident luminal bacteria while being also able to mount inflammatory responses against pathogens. Toll-like receptors (TLRs) are a major class of PRRs that are present on IECs and immune cells which are involved in the induction of both tolerance and inflammation. A growing body of experimental and clinical evidence supports the therapeutic and preventive application of probiotics for several gastrointestinal inflammatory disorders in which TLRs exert a significant role. This review aims to summarize the current knowledge of the beneficial effects of probiotic microorganisms with the capacity to modulate the immune system (immunobiotics) in the regulation of intestinal inflammation in pigs, which are very important as both livestock and human model. Especially we discuss the role of TLRs, their signaling pathways, and their negative regulators in both the inflammatory intestinal injury and the beneficial effects of immunobiotics in general, and Lactobacillus jensenii TL2937 in particular. This review article emphasizes the cellular and molecular interactions of immunobiotics with IECs and immune cells through TLRs and their application for improving animal and human health.
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Affiliation(s)
- Julio Villena
- Immunobiotics Research Group , Tucuman , Argentina ; Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET) , Tucuman , Argentina
| | - Haruki Kitazawa
- Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University , Sendai , Japan
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Juarez GE, Villena J, Salva S, de Valdez GF, Rodriguez AV. Lactobacillus reuteri CRL1101 beneficially modulate lipopolysaccharide-mediated inflammatory response in a mouse model of endotoxic shock. J Funct Foods 2013. [DOI: 10.1016/j.jff.2013.08.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
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20
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Sung MK, Park MY. Nutritional modulators of ulcerative colitis: Clinical efficacies and mechanistic view. World J Gastroenterol 2013; 19:994-1004. [PMID: 23467687 PMCID: PMC3582011 DOI: 10.3748/wjg.v19.i7.994] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Revised: 11/17/2012] [Accepted: 12/27/2012] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is an inflammation-associated disease of the colon and rectum. The onset and progress of the disease are directly influenced by the nature of the intestinal microflora, the intestinal barrier function, and the immunological responses of the host. The epithelial invasion of pathogenic bacteria due to excess contact and/or barrier dysfunction is related to inflammation mediated by intestinal immune responses. Although the etiology of UC is not clearly understood, recent studies have shown a rising incidence of UC worldwide, and this phenomenon is more prominent in Asian countries and in Asian immigrants in Western countries. The increased prevalence of UC also contributes to an increased risk of developing colorectal cancer. Environmental factors, including changes in dietary habits, have been suggested as major risk factors of UC. A systematic review showed a negative association between UC risk and vegetable intake, whereas total fat, omega-6 fatty acids and meat intake were positively associated with an increased risk of UC. Individual dietary factors and energy balance have been suggested as having important roles in inducing changes in the microbial population and intestinal barrier integrity and in regulating inflammatory immune responses, directly or indirectly. Excess energy intake is now known to increase pathogenic microbial populations. Likewise, the application of appropriate probiotics may reverse the pathogenic progression of the disease. In the meantime, dietary anti-inflammatory compounds, including omega-3 fatty acids and other phytochemicals, may directly suppress inflammatory responses in the course of UC development. In this review, the increased prevalence of UC and its management are interpreted from the standpoint of nutritional modulation to regulate the intestinal microflora population, intestinal epithelium permeability, and inflammatory responses.
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21
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Zhao JJ, Feng XP, Zhang XL, Le KY. Effect of Porphyromonas gingivalis and Lactobacillus acidophilus on secretion of IL1B, IL6, and IL8 by gingival epithelial cells. Inflammation 2013; 35:1330-7. [PMID: 22382516 DOI: 10.1007/s10753-012-9446-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Porphyromonas gingivalis alters cytokine expression in gingival epithelial cells, stimulating inflammatory responses that may lead to periodontal disease. This study explored the effect of Lactobacillus acidophilus on the specific expressions of the interleukins (ILs) IL1B, IL6, and IL8 induced by the pathogen. Human gingival epithelial cells were co-cultured with P. gingivalis, L. acidophilus, or L. acidophilus + P. gingivalis; the control group consisted of the cells alone. Protein and gene expression levels of the ILs were detected using ELISA and qRT-PCR, respectively. The supernatant from the P. gingivalis group held significantly higher protein and mRNA levels of IL1B, IL6, and IL8, compared to the control group. In the mixed bacterial group (L. acidophilus + P. gingivalis), the levels of all three ILs decreased with increasing concentrations of L. acidophilus and were significantly different from the P. gingivalis group. This suggests that in gingival cells, L. acidophilus offsets the P. gingivalis-induced secretion of these ILs in a dose-dependent manner.
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Affiliation(s)
- Jun-jun Zhao
- Shanghai Key Laboratory of Stomatology, 9th People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200011, People's Republic of China
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22
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Saad N, Delattre C, Urdaci M, Schmitter J, Bressollier P. An overview of the last advances in probiotic and prebiotic field. Lebensm Wiss Technol 2013. [DOI: 10.1016/j.lwt.2012.05.014] [Citation(s) in RCA: 174] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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23
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Immunobiotic Lactobacillus jensenii modulates the Toll-like receptor 4-induced inflammatory response via negative regulation in porcine antigen-presenting cells. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2012; 19:1038-53. [PMID: 22573738 DOI: 10.1128/cvi.00199-12] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Previously, we demonstrated that Lactobacillus jensenii TL2937 attenuates the inflammatory response triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal epithelial cells. In view of the critical importance of antigen-presenting cell (APC) polarization in immunoregulation, the objective of the present study was to examine the effect of strain TL2937 on the activation patterns of APCs from swine Peyer's patches (PPs). We demonstrated that direct exposure of porcine APCs to L. jensenii in the absence of inflammatory signals increased expression of interleukin-10 (IL-10) and transforming growth factor β in CD172a(+) APCs and caused them to display tolerogenic properties. In addition, pretreatment of CD172a(+) APCs with L. jensenii resulted in differential modulation of the production of pro- and anti-inflammatory cytokines in response to TLR4 activation. The immunomodulatory effect of strain TL2937 was not related to a downregulation of TLR4 but was related to an upregulation of the expression of three negative regulators of TLRs: single immunoglobulin IL-1-related receptor (SIGIRR), A20, and interleukin-1 receptor-associated kinase M (IRAK-M). Our results also indicated that TLR2 has an important role in the anti-inflammatory activity of L. jensenii TL2937, since anti-TLR2 antibodies blocked the upregulation of SIGIRR and IRAK-M in CD172a(+) APCs and the production of IL-10 in response to TLR4 activation. We performed, for the first time, a precise functional characterization of porcine APCs from PPs, and we demonstrated that CD172a(+) cells were tolerogenic. Our findings demonstrate that adherent cells and isolated CD172a(+) cells harvested from swine PPs were useful for in vitro study of the inflammatory responses in the porcine gut and the immunomodulatory effects of immunobiotic microorganisms.
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Langa S, Maldonado-Barragán A, Delgado S, Martín R, Martín V, Jiménez E, Ruíz-Barba JL, Mayo B, Connor RI, Suárez JE, Rodríguez JM. Characterization of Lactobacillus salivarius CECT 5713, a strain isolated from human milk: from genotype to phenotype. Appl Microbiol Biotechnol 2012; 94:1279-87. [DOI: 10.1007/s00253-012-4032-1] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2012] [Revised: 03/08/2012] [Accepted: 03/15/2012] [Indexed: 11/28/2022]
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25
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Verbeek R, Bsibsi M, Plomp A, van Neerven RJJ, te Biesebeke R, van Noort JM. Late rather than early responses of human dendritic cells highlight selective induction of cytokines, chemokines and growth factors by probiotic bacteria. Benef Microbes 2011; 1:109-19. [PMID: 21840799 DOI: 10.3920/bm2009.0026] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The probiotic properties of commensal bacteria including lactobacilli and bifidobacteria are likely to be determined at least in part by their effects on dendritic cells. Like traditional immune stimulants such as lipopolysaccharides (LPS), probiotic bacteria promote maturation of cultured human dendritic cells (DC) by inducing elevated expression of MHC-II and co-stimulatory molecules. Different effects have been reported on cytokine induction, especially of major regulatory cytokines such as TNF-α, IL-12 and IL-10. Yet, these previous analyses have failed to reveal consistent differences between such effects of probiotics on the one hand, and of LPS on the other. Selective response markers for probiotics, however, would be important for our understanding of their biological properties and for a rational selection of strains for in vivo studies. In this study, we compared in detail both early and late effects on cultured human DC of 4 different probiotics with those of LPS. At the early stages of stimulation, all stimuli induced qualitatively very similar responses in DC at the level of surface markers and secretion of cytokines and chemokines. A lower immune stimulatory effect was observed by Bifidobacterium animalis BB-12 as compared to lactobacilli. Late responses, on the other hand, tended to diverge. Microarray transcript profiling for 268 cytokines, chemokines, growth factors and their receptors after 2 days of culture revealed various transcripts to be selectively induced by certain probiotics but not LPS. Our data indicate that late rather than early DC responses may be helpful to clarify the divergent biological effects of probiotics on human innate immune responses.
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Affiliation(s)
- R Verbeek
- TNO Quality of Life, Leiden, the Netherlands
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26
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Ha EM. The Impact of Gut Microbiota in Human Health and Diseases: Implication for Therapeutic Potential. Biomol Ther (Seoul) 2011. [DOI: 10.4062/biomolther.2011.19.2.155] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
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27
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Ng SC, Plamondon S, Kamm MA, Hart AL, Al-Hassi HO, Guenther T, Stagg AJ, Knight SC. Immunosuppressive effects via human intestinal dendritic cells of probiotic bacteria and steroids in the treatment of acute ulcerative colitis. Inflamm Bowel Dis 2010; 16:1286-98. [PMID: 20155842 DOI: 10.1002/ibd.21222] [Citation(s) in RCA: 101] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND In ulcerative colitis (UC) gut bacteria drive inflammation. Bacterial recognition and T-cell responses are shaped by intestinal dendritic cells (DCs); therapeutic effects of probiotic bacteria may relate to modulation of intestinal DC. The probiotic mixture, VSL#3, increases interleukin (IL)-10 and downregulates IL-12p40 production by DC in vitro. We evaluated in vivo effects of oral VSL#3 and steroids on colonic DC in patients with acute UC. METHODS Rectal biopsies were obtained from patients with active UC before and after treatment with VSL#3, corticosteroids, or placebo, and from healthy controls. Myeloid colonic DC were studied from freshly isolated lamina propria cells using multicolor flow cytometry. Surface expression of activation markers, CD40, CD86, pattern recognition receptors, Toll-like receptor (TLR)-2 and TLR-4 were assessed. Changed function was measured from ongoing intracellular IL-10, IL-12p40, IL-6, and IL-13 production. RESULTS Acute UC colonic myeloid DC were producing more IL-10 and IL-12p40 than control DC (P = 0.01). In VSL#3-treated patients DC TLR-2 expression decreased (P < 0.05), IL-10 production increased and IL-12p40 production decreased (P < 0.005); 10/14 patients on VSL#3 showed a clinical response. Corticosteroids also resulted in increased IL-10 and reduced IL-12p40 production by DC. Conversely, in patients on placebo, TLR-2 expression and intensity of staining for IL-12p40 and IL-6 increased (all P < 0.05); 5/14 patients on placebo showed a clinical response (P = NS). CONCLUSIONS Despite small numbers of human colonic DC available, we showed that treatment of UC patients with probiotic VSL#3 and corticosteroids induced "favorable" intestinal DC function in vivo, increasing regulatory cytokines and lowering proinflammatory cytokines and TLR expression. These effects may contribute to therapeutic benefit.
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Affiliation(s)
- Siew C Ng
- Antigen Presentation Research Group, Faculty of Medicine, Imperial College London, Northwick Park and St Mark's Campus, Watford Road, Harrow, UK
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Hol J, de Jongste JC, Nieuwenhuis EE. Quoting a landmark paper on the beneficial effects of probiotics. J Allergy Clin Immunol 2010; 124:1354-6.e9. [PMID: 19818483 DOI: 10.1016/j.jaci.2009.07.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2009] [Revised: 07/21/2009] [Accepted: 07/23/2009] [Indexed: 02/06/2023]
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Roles of capsule and lipopolysaccharide O antigen in interactions of human monocyte-derived dendritic cells and Klebsiella pneumoniae. Infect Immun 2009; 78:210-9. [PMID: 19841082 DOI: 10.1128/iai.00864-09] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
In humans, Klebsiella pneumoniae is a saprophytic bacterium of the nasopharyngeal and intestinal mucosae that is also frequently responsible for severe nosocomial infections. Two major factors of virulence, capsular polysaccharide (CPS) and lipopolysaccharide (LPS) O antigen, are involved in mucosal colonization and the development of infections. These bacterial surface structures are likely to play major roles in interactions with the mucosal immune system, which are orchestrated by a network of surveillance based on dendritic cells (DCs). To determine the roles of K. pneumoniae CPS and LPS in the DC response, we investigated the response of immature human monocyte-derived DCs to bacterial challenge with a wild-type strain and its isogenic mutants deficient in CPS or LPS O-antigen production. As observed by flow cytometry and confocal laser microscopy, the rate of phagocytosis was inversely proportional to the amount of CPS on the bacterial cell surface, with LPS playing little or no role. The K. pneumoniae wild-type strain induced DC maturation with upregulation of CD83, CD86, and TLR4 and downregulation of CD14 and DC-SIGN. With CPS mutants, we observed a greater decrease in DC-SIGN, suggesting a superior maturation of DCs. In addition, incubation of DCs with CPS mutants, and to a lesser extent with LPS mutants, resulted in significantly higher Th1 cytokine production. Combined, our findings suggest that K. pneumoniae CPS, by hampering bacterial binding and internalization, induces a defective immunological host response, including maturation of DCs and pro-Th1 cytokine production, whereas the LPS O antigen seems to be involved essentially in DC activation.
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Borchers AT, Selmi C, Meyers FJ, Keen CL, Gershwin ME. Probiotics and immunity. J Gastroenterol 2009; 44:26-46. [PMID: 19159071 DOI: 10.1007/s00535-008-2296-0] [Citation(s) in RCA: 306] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2008] [Accepted: 09/03/2008] [Indexed: 02/04/2023]
Abstract
Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, including the gastrointestinal tract. While this beneficial effect was originally thought to stem from improvements in the intestinal microbial balance, there is now substantial evidence that probiotics can also provide benefits by modulating immune functions. In animal models, probiotic supplementation is able to provide protection from spontaneous and chemically induced colitis by downregulating inflammatory cytokines or inducing regulatory mechanisms in a strain-specific manner. In animal models of allergen sensitization and murine models of asthma and allergic rhinitis, orally administered probiotics can strain-dependently decrease allergen-specific IgE production, in part by modulating systemic cytokine production. Certain probiotics have been shown to decrease airway hyperresponsiveness and inflammation by inducing regulatory mechanisms. Promising results have been obtained with probiotics in the treatment of human inflammatory diseases of the intestine and in the prevention and treatment of atopic eczema in neonates and infants. However, the findings are too variable to allow firm conclusions as to the effectiveness of specific probiotics in these conditions.
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Affiliation(s)
- Andrea T Borchers
- Department of Nutrition, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA
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31
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Ng SC, Hart AL, Kamm MA, Stagg AJ, Knight SC. Mechanisms of action of probiotics: recent advances. Inflamm Bowel Dis 2009; 15:300-10. [PMID: 18626975 DOI: 10.1002/ibd.20602] [Citation(s) in RCA: 323] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The intestinal microbiota plays a fundamental role in maintaining immune homeostasis. In controlled clinical trials probiotic bacteria have demonstrated a benefit in treating gastrointestinal diseases, including infectious diarrhea in children, recurrent Clostridium difficile-induced infection, and some inflammatory bowel diseases. This evidence has led to the proof of principle that probiotic bacteria can be used as a therapeutic strategy to ameliorate human diseases. The precise mechanisms influencing the crosstalk between the microbe and the host remain unclear but there is growing evidence to suggest that the functioning of the immune system at both a systemic and a mucosal level can be modulated by bacteria in the gut. Recent compelling evidence has demonstrated that manipulating the microbiota can influence the host. Several new mechanisms by which probiotics exert their beneficial effects have been identified and it is now clear that significant differences exist between different probiotic bacterial species and strains; organisms need to be selected in a more rational manner to treat disease. Mechanisms contributing to altered immune function in vivo induced by probiotic bacteria may include modulation of the microbiota itself, improved barrier function with consequent reduction in immune exposure to microbiota, and direct effects of bacteria on different epithelial and immune cell types. These effects are discussed with an emphasis on those organisms that have been used to treat human inflammatory bowel diseases in controlled clinical trials.
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Affiliation(s)
- S C Ng
- Antigen Presentation Research Group, Imperial College London, London, UK
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32
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Konstantinov SR, Smidt H, de Vos WM, Bruijns SCM, Singh SK, Valence F, Molle D, Lortal S, Altermann E, Klaenhammer TR, van Kooyk Y. S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc Natl Acad Sci U S A 2008; 105:19474-9. [PMID: 19047644 PMCID: PMC2592362 DOI: 10.1073/pnas.0810305105] [Citation(s) in RCA: 410] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2008] [Indexed: 12/17/2022] Open
Abstract
Dendritic cells (DCs) are antigen-presenting cells that play an essential role in mucosal tolerance. They regularly encounter beneficial intestinal bacteria, but the nature of these cellular contacts and the immune responses elicited by the bacteria are not entirely elucidated. Here, we examined the interactions of Lactobacillus acidophilus NCFM and its cell surface compounds with DCs. L. acidophilus NCFM attached to DCs and induced a concentration-dependent production of IL-10, and low IL-12p70. We further demonstrated that the bacterium binds to DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a DC- specific receptor. To identify the DC-SIGN ligand present on the bacterium, we took advantage of a generated array of L. acidophilus NCFM mutants. A knockout mutant of L. acidophilus NCFM lacking the surface (S) layer A protein (SlpA) was significantly reduced in binding to DC-SIGN. This mutant incurred a chromosomal inversion leading to dominant expression of a second S layer protein, SlpB. In the SlpB-dominant strain, the nature of the interaction of this bacterium with DCs changed dramatically. Higher concentrations of proinflammatory cytokines such as IL-12p70, TNFalpha, and IL-1beta were produced by DCs interacting with the SlpB-dominant strain compared with the parent NCFM strain. Unlike the SlpA-knockout mutant, T cells primed with L. acidophilus NCFM stimulated DCs produced more IL-4. The SlpA-DC-SIGN interaction was further confirmed as purified SlpA protein ligated directly to the DC-SIGN. In conclusion, the major S layer protein, SlpA, of L. acidophilus NCFM is the first probiotic bacterial DC-SIGN ligand identified that is functionally involved in the modulation of DCs and T cells functions.
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Affiliation(s)
- Sergey R. Konstantinov
- Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB, Wageningen, The Netherlands
- VU University Medical Center Amsterdam, v.d. Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
| | - Hauke Smidt
- Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB, Wageningen, The Netherlands
| | - Willem M. de Vos
- Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB, Wageningen, The Netherlands
- Department of Basic Veterinary Sciences, Helsinki University, FIN-00014, Helsinki, Finland
| | - Sven C. M. Bruijns
- VU University Medical Center Amsterdam, v.d. Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
| | - Satwinder Kaur Singh
- VU University Medical Center Amsterdam, v.d. Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
| | - Florence Valence
- Institut National de la Recherche Agronomique, 65 rue de Saint Brieuc, 35000 Rennes, France; and
| | - Daniel Molle
- Institut National de la Recherche Agronomique, 65 rue de Saint Brieuc, 35000 Rennes, France; and
| | - Sylvie Lortal
- Institut National de la Recherche Agronomique, 65 rue de Saint Brieuc, 35000 Rennes, France; and
| | | | - Todd R. Klaenhammer
- Department of Microbiology and
- Southeast Dairy Foods Research Center, North Carolina State University, Raleigh, NC 27695
| | - Yvette van Kooyk
- VU University Medical Center Amsterdam, v.d. Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
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Vanderpool C, Yan F, Polk DB. Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases. Inflamm Bowel Dis 2008; 14:1585-96. [PMID: 18623173 DOI: 10.1002/ibd.20525] [Citation(s) in RCA: 221] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Probiotics are defined as nonpathogenic living microorganisms, including some commensal bacterial flora, which have beneficial effects on host health and disease prevention and/or treatment. Clinical trials have shown beneficial effects of probiotics on several human diseases, such as inflammatory bowel diseases (IBDs), which are among the most-studied diseases testing probiotics as a potential therapy. However, a significant question regarding clinical use of probiotics is the mechanism underlying the wide range of actions. Studies discussed in this review suggest 3 distinct cellular and molecular mechanisms for probiotic regulation in IBD therapy: 1) Probiotics block pathogenic bacterial effects by producing bactericidal substances and competing with pathogens and toxins for adherence to the intestinal epithelium; 2) Probiotics regulate immune responses by enhancing the innate immunity and modulating pathogen-induced inflammation via toll-like receptor-regulated signaling pathways; and 3) Probiotics regulate intestinal epithelial homeostasis by promoting intestinal epithelial cell survival, enhancing barrier function, and stimulating protective responses. Probiotics modulate host cell signaling pathways, including Akt, mitogen-activated protein kinases, and nuclear factor-kappaB to mediate these intestinal epithelial functions. It is hoped that developing a mechanistic understanding of probiotic action will provide the rationale to support the development of new hypothesis-driven studies to define the clinical efficacy in preventive, adjunctive, or alternative treatments for IBD.
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Affiliation(s)
- Charles Vanderpool
- Department of Pediatrics, Division of Gastroenterology, Hepatology & Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0696, USA
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Oral immunization with recombinant lactobacillus plantarum induces a protective immune response in mice with Lyme disease. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2008; 15:1429-35. [PMID: 18632920 PMCID: PMC2546682 DOI: 10.1128/cvi.00169-08] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Mucosal immunization is advantageous over other routes of antigen delivery because it can induce both mucosal and systemic immune responses. Our goal was to develop a mucosal delivery vehicle based on bacteria generally regarded as safe, such as Lactobacillus spp. In this study, we used the Lyme disease mouse model as a proof of concept. We demonstrate that an oral vaccine based on live recombinant Lactobacillus plantarum protects mice from tick-transmitted Borrelia burgdorferi infection. Our method of expressing vaccine antigens in L. plantarum induces both systemic and mucosal immunity after oral administration. This platform technology can be applied to design oral vaccine delivery vehicles against several microbial pathogens.
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Hoarau C, Martin L, Faugaret D, Baron C, Dauba A, Aubert-Jacquin C, Velge-Roussel F, Lebranchu Y. Supernatant from bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells. PLoS One 2008; 3:e2753. [PMID: 18648505 PMCID: PMC2447180 DOI: 10.1371/journal.pone.0002753] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2008] [Accepted: 06/20/2008] [Indexed: 01/01/2023] Open
Abstract
Background Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, the signaling pathways engaged by probiotics are poorly understood. We have previously reported that a fermentation product from Bifidobacterium breve C50 (BbC50sn) could induce maturation, high IL-10 production and prolonged survival of DCs via a TLR2 pathway. We therefore studied the roles of mitogen-activated protein kinases (MAPK), glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K) pathways on biological functions of human monocyte-derived DCs treated with BbC50sn. Methodology/Principal Findings DCs were differentiated from human monocytes with IL-4 and GM-CSF for 5 days and cultured with BbC50sn, lipopolysaccharide (LPS) or Zymosan, with or without specific inhibitors of p38MAPK (SB203580), ERK (PD98059), PI3K (LY294002) and GSK3 (SB216763). We found that 1) the PI3K pathway was positively involved in the prolonged DC survival induced by BbC50sn, LPS and Zymosan in contrast to p38MAPK and GSK3 which negatively regulated DC survival; 2) p38MAPK and PI3K were positively involved in DC maturation, in contrast to ERK and GSK3 which negatively regulated DC maturation; 3) ERK and PI3K were positively involved in DC-IL-10 production, in contrast to GSK3 that was positively involved in DC-IL-12 production whereas p38MAPK was positively involved in both; 4) BbC50sn induced a PI3K/Akt phosphorylation similar to Zymosan and a p38MAPK phosphorylation similar to LPS. Conclusion/Significance We report for the first time that a fermentation product of a bifidobacteria can differentially activate MAPK, GSK3 and PI3K in order to modulate DC biological functions. These results give new insights on the fine-tuned balance between the maintenance of normal mucosal homeostasis to commensal and probiotic bacteria and the specific inflammatory immune responses to pathogen bacteria.
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Affiliation(s)
- Cyrille Hoarau
- UPRES EA 4245 Cellules Dendritiques & Greffes, Université François-Rabelais, Tours, France.
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Baba N, Samson S, Bourdet-Sicard R, Rubio M, Sarfati M. Commensal bacteria trigger a full dendritic cell maturation program that promotes the expansion of non-Tr1 suppressor T cells. J Leukoc Biol 2008; 84:468-76. [PMID: 18511576 DOI: 10.1189/jlb.0108017] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Dendritic cells (DCs) orchestrate the immune response establishing immunity versus tolerance. These two opposite functions may be dictated by DC maturation status with maturity linked to immunogenicity. DCs directly interact with trillions of noninvasive intestinal bacteria in vivo, a process that contributes to gut homeostasis. We here evaluated the maturation program elicited in human DCs by direct exposure to commensal-related bacteria (CB) in the absence of inflammatory signals. We showed that eight gram(+) and gram(-) CB strains up-regulated costimulatory molecule expression in DCs and provoked a chemokine receptor switch similar to that activated by gram(+) pathogens. CB strains may be classified into three groups according to DC cytokine release: high IL-12 and low IL-10; low IL-12 and high IL-10; and low IL-12 and IL-10. All CB-treated DCs produced IL-1beta and IL-6 and almost no TGF-beta. Yet, CB instructed DCs to convert naive CD4+ T cells into hyporesponsive T cells that secreted low or no IFN-gamma, IL-10, and IL-17 and instead, displayed suppressor function. These data demonstrate that phenotypic DC maturation combined to an appropriate cytokine profile is insufficient to warrant Th1, IL-10-secreting T regulatory Type 1 (Tr1), or Th17 polarization. We propose that commensal flora and as such, probiotics manipulate DCs by a yet-unidentified pathway to enforce gut tolerance.
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Affiliation(s)
- Nobuyasu Baba
- Immunoregulation Laboratory, Centre Hospitalier de l'Université de Montréal Research Center, University of Montréal, Québec, Canada
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Ratajczak C, Duez C, Grangette C, Pochard P, Tonnel AB, Pestel J. Impact of lactic Acid bacteria on dendritic cells from allergic patients in an experimental model of intestinal epithelium. J Biomed Biotechnol 2007; 2007:71921. [PMID: 17497025 PMCID: PMC1847481 DOI: 10.1155/2007/71921] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2006] [Revised: 12/04/2006] [Accepted: 12/06/2006] [Indexed: 11/17/2022] Open
Abstract
Lactic acid bacteria (LAB) are Gram positive nonpathogenic commensal organisms present in human gastrointestinal tract. In vivo, LAB are separated from antigen-presenting cells such as dendritic cells (DC) by the intestinal epithelial barrier. In this study, the impact of one LAB strain (Lactobacillus casei ATCC393) on human monocyte-derived DC from allergic and healthy donors was assessed by using a polarized epithelium model. Confocal and flow cytometer analyses showed that immature DC efficiently captured FITC-labelled L. casei through the epithelial layer. After interaction with L. casei, DC acquired a partial maturation status (i.e., CD86 and CD54 increase) and increased their interleukin (IL)-10 and IL-12 production. Interestingly, after activation by L. casei in the presence of experimental epithelium, DC from allergic patients instructed autologous naïve CD4(+) T cells to produce more interferon-gamma than without the epithelium. Thus by modulating human DC reactivity, LAB and intestinal epithelium might modify T cell immune response and regulate the development of allergic reaction.
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Affiliation(s)
- Céline Ratajczak
- Institut National de la Santé et de la Recherche Médicale (INSERM) U 416, Institut Fédératif de Recherche 17 (IFR 17), Institut Pasteur de Lille, 59019 Lille, France
- Institut Pasteur de Lille, 59019 Lille, France
- Université de Lille 2, 59800 Lille, France
| | - Catherine Duez
- Institut National de la Santé et de la Recherche Médicale (INSERM) U 416, Institut Fédératif de Recherche 17 (IFR 17), Institut Pasteur de Lille, 59019 Lille, France
- Institut Pasteur de Lille, 59019 Lille, France
- Université de Lille 2, 59800 Lille, France
| | - Corinne Grangette
- Bactéries Lactiques et Immunité des Muqueuses, Institut Pasteur de Lille, 59019 Lille, France
| | - Pierre Pochard
- Institut National de la Santé et de la Recherche Médicale (INSERM) U 416, Institut Fédératif de Recherche 17 (IFR 17), Institut Pasteur de Lille, 59019 Lille, France
- Institut Pasteur de Lille, 59019 Lille, France
- Université de Lille 2, 59800 Lille, France
- The Department of Immunology, Faculty of Medicine, University of Manitoba, Basic Medical Sciences Building, Winnipeg, MB, Canada R3E 0W3
| | - André-Bernard Tonnel
- Institut National de la Santé et de la Recherche Médicale (INSERM) U 416, Institut Fédératif de Recherche 17 (IFR 17), Institut Pasteur de Lille, 59019 Lille, France
- Institut Pasteur de Lille, 59019 Lille, France
- Université de Lille 2, 59800 Lille, France
| | - Joël Pestel
- Institut National de la Santé et de la Recherche Médicale (INSERM) U 416, Institut Fédératif de Recherche 17 (IFR 17), Institut Pasteur de Lille, 59019 Lille, France
- Institut Pasteur de Lille, 59019 Lille, France
- Université de Lille 2, 59800 Lille, France
- *Joël Pestel:
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Milano F, van Baal JWPM, Rygiel AM, Bergman JJGHM, Van Deventer SJH, Kapsenberg ML, Peppelenbosch MP, Krishnadath KK. An improved protocol for generation of immuno-potent dendritic cells through direct electroporation of CD14+ monocytes. J Immunol Methods 2007; 321:94-106. [PMID: 17336322 DOI: 10.1016/j.jim.2007.01.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2006] [Revised: 01/09/2007] [Accepted: 01/10/2007] [Indexed: 10/23/2022]
Abstract
In this study we demonstrate a novel protocol showing that electroporation of CD14+ monocytes directly isolated from blood with green fluorescent protein (GFP) RNA results in a 3-fold higher yield of antigen presenting dendritic cells (DCs) when compared to conventional methods employing immature DCs for electroporation. We further show a stable electroporation efficacy resulting in 60% of GFP positive cells. Expression of co-stimulatory molecules and maturation markers such as CD80, CD86, CD83 as well of the chemokine receptor 7 (CCR7) was found in 90% of the mature DCs. Importantly, production of IL-12p70 was 10 times higher in cells electroporated at the monocyte stage compared to cells electroporated at the immature DC stage. Stimulation of autologous naïve lymphocytes by DCs electroporated at monocytes stage elicited proliferation of CD8+ T-cell with 7-fold increase in IFN-gamma release. Blocking of the MHC-Class I molecules significantly inhibited the IFN-gamma release, indicating that antigen presentation was MHC-Class I mediated. In summary, electroporation of CD14+ monocytes with RNA results in a high yield of antigen presenting DCs with high immuno-stimulatory capacity and antigen presentation on MHC-Class I molecules. This improved method may represent an attractive approach for RNA-based DC immunotherapy.
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Affiliation(s)
- Francesca Milano
- Department of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
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Ciabattini A, Cuppone AM, Pulimeno R, Iannelli F, Pozzi G, Medaglini D. Stimulation of human monocytes with the gram-positive vaccine vector Streptococcus gordonii. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2006; 13:1037-43. [PMID: 16960116 PMCID: PMC1563572 DOI: 10.1128/cvi.00110-06] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Streptococcus gordonii is a bacterial vaccine vector which has previously been shown to activate dendritic cells in vitro and to induce local and systemic immune responses in vivo. In the present study, human monocytes (THP-1 cell line and peripheral blood monocytes) were characterized following interaction with S. gordonii. Treatment of human monocytes with S. gordonii but not latex beads induced a clear up-regulation of CD83, CD40, CD80, and CD54 and the down-regulation of CD14. Furthermore, bacterial treatment stimulated an increased expression of Toll-like receptor 5 (TLR5), TLR6, and TLR7, production of the proinflammatory cytokines tumor necrosis factor alpha and interleukin 1 beta, and reduction of the phagocytic activity. This work shows that the immunostimulatory activity of S. gordonii is not restricted to induction of dendritic-cell maturation but also affects the differentiation process of human monocytes.
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Affiliation(s)
- Annalisa Ciabattini
- Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena, 53100 Siena, Italy
| | - Anna Maria Cuppone
- Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena, 53100 Siena, Italy
| | - Rita Pulimeno
- Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena, 53100 Siena, Italy
| | - Francesco Iannelli
- Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena, 53100 Siena, Italy
| | - Gianni Pozzi
- Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena, 53100 Siena, Italy
| | - Donata Medaglini
- Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena, 53100 Siena, Italy
- Corresponding author. Mailing address: Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biologia Molecolare, Università di Siena, Policlinico Le Scotte, Viale Bracci, 53100 Siena, Italy. Phone: 39 0577 233307. Fax: 39 0577 233334. E-mail:
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Doron S, Gorbach SL. Probiotics: their role in the treatment and prevention of disease. Expert Rev Anti Infect Ther 2006; 4:261-75. [PMID: 16597207 DOI: 10.1586/14787210.4.2.261] [Citation(s) in RCA: 100] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
A probiotic is a "live microbial food ingredients that, when ingested in sufficient quantities, exerts health benefits on the consumer". Probiotics exert their benefits through several mechanisms; they prevent colonization, cellular adhesion and invasion by pathogenic organisms, they have direct antimicrobial activity and they modulate the host immune response. The strongest evidence for the clinical effectiveness of probiotics has been in their use for the prevention of symptoms of lactose intolerance, treatment of acute diarrhea, attenuation of antibiotic-associated gastrointestinal side effects and the prevention and treatment of allergy manifestations. More research needs to be carried out to clarify conflicting findings on the use of probiotics for prevention of travelers' diarrhea, infections in children in daycare and dental caries, and elimination of nasal colonization with potentially pathogenic bacteria. Promising ongoing research is being conducted on the use of probiotics for the treatment of Clostridium difficile colitis, treatment of Helicobacter pylori infection, treatment of inflammatory bowel disease and prevention of relapse, treatment of irritable bowel syndrome, treatment of intestinal inflammation in cystic fibrosis patients, and prevention of necrotizing enterocolitis in premature infants. Finally, areas of future research include the use of probiotics for the treatment of rheumatoid arthritis, prevention of cancer and the treatment of graft-versus-host disease in bone marrow transplant recipients.
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Affiliation(s)
- Shira Doron
- Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Boston, MA 02111, USA.
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Saxelin M, Tynkkynen S, Mattila-Sandholm T, de Vos WM. Probiotic and other functional microbes: from markets to mechanisms. Curr Opin Biotechnol 2005; 16:204-11. [PMID: 15831388 DOI: 10.1016/j.copbio.2005.02.003] [Citation(s) in RCA: 248] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Insight into the diversity and function of the human intestinal microbiota has been stimulated by clinical studies with bacteria that exhibit specific functions and which are marketed as probiotics to positively affect our health. Initial efforts concentrated on establishing sound scientific support for the efficacy of these probiotic bacteria, which mainly include Lactobacillus and Bifidobacterium species. Following these evidence-based functional approaches, considerable research is now focused on the mechanisms of action of probiotic bacteria. The mechanisms identified to date mainly relate to the stimulation of host defence systems, immune modulation and the competitive exclusion of pathogens. Recent efficacy, molecular and genomics-based studies have also been reported for some probiotic strains that have found their position in the market place.
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Affiliation(s)
- Maija Saxelin
- Valio Ltd, R&D, Meijeritie 4A, PO Box 30, 00039 Valio, Helsinki, Finland
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Klaenhammer TR, Barrangou R, Buck BL, Azcarate-Peril MA, Altermann E. Genomic features of lactic acid bacteria effecting bioprocessing and health. FEMS Microbiol Rev 2005. [DOI: 10.1016/j.fmrre.2005.04.007] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
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Renkl AC, Wussler J, Ahrens T, Thoma K, Kon S, Uede T, Martin SF, Simon JC, Weiss JM. Osteopontin functionally activates dendritic cells and induces their differentiation toward a Th1-polarizing phenotype. Blood 2005; 106:946-55. [PMID: 15855273 DOI: 10.1182/blood-2004-08-3228] [Citation(s) in RCA: 130] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Osteopontin (OPN) has been shown to have T helper 1 (Th1) cytokine functions in cell-mediated immunity. Deficiency of OPN is linked to a reduced Th1 immune response in autoimmunity, infectious disease, and delayed-type allergy. Dendritic cells (DCs) are central for the induction of T-cell-mediated immunity, when initially flexible DCs are instructed by priming signals and tissue-derived factors to adopt Th1, Th2, or regulatory T-cell-inducing phenotypes. Although OPN influences the cytokine secretion of T cells and macrophages, its effects on DC polarization remain an important missing link in the understanding of OPN functions in Th1 immunity. Here we demonstrate that OPN promotes the emigration of human DCs from the epidermis and functionally activates myeloid-type DCs, augmenting their expression of HLA-DR, costimulatory, and adhesion molecules. OPN induces their Th1-promoting tumor necrosis factor alpha (TNF-alpha) and interleukin-12 (IL-12) secretion, and enhances their allostimulatory capacity. In mixed lymphocyte reactions (MLRs), OPN stimulates IL-12 secretion by DCs, inducing elevated interferon-gamma (IFN-gamma) production by T cells. Naive Th cells stimulated by OPN-activated DCs show a Th1-polarized cytokine production. Our findings identify OPN as an important tissue-derived factor that DCs encounter when traveling from peripheral sites of activation to secondary lymphatic organs, which induces DC maturation toward a Th1-promoting phenotype.
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Affiliation(s)
- Andreas C Renkl
- University of Ulm, Department of Dermatology and Allergology, Maienweg 12, 89081 Ulm, Germany.
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Mohamadzadeh M, Olson S, Kalina WV, Ruthel G, Demmin GL, Warfield KL, Bavari S, Klaenhammer TR. Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization. Proc Natl Acad Sci U S A 2005; 102:2880-5. [PMID: 15710900 PMCID: PMC549474 DOI: 10.1073/pnas.0500098102] [Citation(s) in RCA: 338] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Professional antigen-presenting dendritic cells (DCs) are critical in regulating T cell immune responses at both systemic and mucosal sites. Many Lactobacillus species are normal members of the human gut microflora and most are regarded as safe when administered as probiotics. Because DCs can naturally or therapeutically encounter lactobacilli, we investigated the effects of several well defined strains, representing three species of Lactobacillus on human myeloid DCs (MDCs) and found that they modulated the phenotype and functions of human MDCs. Lactobacillus-exposed MDCs up-regulated HLA-DR, CD83, CD40, CD80, and CD86 and secreted high levels of IL-12 and IL-18, but not IL-10. IL-12 was sustained in MDCs exposed to all three Lactobacillus species in the presence of LPS from Escherichia coli, whereas LPS-induced IL-10 was greatly inhibited. MDCs activated with lactobacilli clearly skewed CD4(+) and CD8(+) T cells to T helper 1 and Tc1 polarization, as evidenced by secretion of IFN-gamma, but not IL-4 or IL-13. These results emphasize a potentially important role for lactobacilli in modulating immunological functions of DCs and suggest that certain strains could be particularly advantageous as vaccine adjuvants, by promoting DCs to regulate T cell responses toward T helper 1 and Tc1 pathways.
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Hanniffy S, Wiedermann U, Repa A, Mercenier A, Daniel C, Fioramonti J, Tlaskolova H, Kozakova H, Israelsen H, Madsen S, Vrang A, Hols P, Delcour J, Bron P, Kleerebezem M, Wells J. Potential and opportunities for use of recombinant lactic acid bacteria in human health. ADVANCES IN APPLIED MICROBIOLOGY 2005; 56:1-64. [PMID: 15566975 DOI: 10.1016/s0065-2164(04)56001-x] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Sean Hanniffy
- Institute of Food Research, Norwich Research Park, Colney, Norwich, NR4 7UA, United Kingdom
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Kalliomäki MA, Isolauri E. Probiotics and down-regulation of the allergic response. Immunol Allergy Clin North Am 2004; 24:739-52, viii. [PMID: 15474869 DOI: 10.1016/j.iac.2004.06.006] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The first clinical trials with probiotics, especially in the treatment of atopic eczema, have yielded encouraging results. Experimental studies have found that probiotics exert strain-specific effects in the intestinal lumen and on epithelial cells and immune cells with anti-allergic potential. These effects include enhancement in antigen degradation and gut barrier function and induction of regulatory and proinflammatory immune responses, the latter of which occurs more likely beyond the intestinal epithelium. Future studies should address more accurately how these and other possible mechanisms operate in the complex gastrointestinal macroenvironment in vivo and how these mechanisms are related to the clinical effects in a dose-dependent manner.
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Affiliation(s)
- Marko A Kalliomäki
- Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Charlestown, MA 02129, USA.
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Lamine F, Eutamène H, Fioramonti J, Buéno L, Théodorou V. Colonic responses to Lactobacillus farciminis treatment in trinitrobenzene sulphonic acid-induced colitis in rats. Scand J Gastroenterol 2004; 39:1250-8. [PMID: 15743003 DOI: 10.1080/00365520410007953] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND It has recently been shown that Lactobacillus farciminis treatment exerts an anti-inflammatory effect in trinitrobenzene sulphonic acid (TNBS)-induced colitis partly through a nitric oxide release by this strain. The aim of this study was to evaluate whether L. farciminis treatment shares also the general mechanisms of action involved in the beneficial effect of probiotics in the colonic inflammatory process. METHODS Rats received L. farciminis for 15 days before and 4 days after intracolonic administration of TNBS or vehicle. The following parameters were evaluated: macroscopic damage of colonic mucosa, myeloperoxidase activity, cytokine mucosal levels, bacterial profile in colonic content and mucosa, bacterial translocation and colonic paracellular permeability. RESULTS In the absence of TNBS, L. farciminis treatment reduced colonic paracellular permeability and increased the IL-10 level in the colonic wall. TNBS administration induced colonic macroscopic damage, associated with an increase of myeloperoxidase activity, bacterial translocation, colonic paracellular permeability and IL-1beta mucosal level, and a decrease in IL-10 mucosal level. Moreover, the bacterial profile of colonic content and mucosa was modified. All these alterations were abolished or significantly reduced by L. farciminis treatment. CONCLUSIONS As previously shown, L. farciminis treatment improves TNBS-induced colitis. This study indicates that, in addition to the nitric oxide released by this bacterial strain, the anti-inflammatory action of L. farciminis involves also normalization of colonic microflora, prevention of bacterial translocation, enhancement of barrier integrity and a decrease in the IL-1beta mucosal level.
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Braat H, van den Brande J, van Tol E, Hommes D, Peppelenbosch M, van Deventer S. Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4+ T cells via modulation of dendritic cell function. Am J Clin Nutr 2004; 80:1618-25. [PMID: 15585777 DOI: 10.1093/ajcn/80.6.1618] [Citation(s) in RCA: 151] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Although it is widely recognized that the intake of so-called probiotic microorganisms is beneficial in chronic mucosal inflammation and topical allergic disease, the immunologic details explaining how such bacteria can exert these effects remain obscure. OBJECTIVE We determined whether Lactobacillus rhamnosus can modulate T cell responses in vitro and in vivo. DESIGN In vitro, human monocyte-derived dendritic cells (DCs) matured in the presence of L. rhamnosus were used to instruct naive CD4+ T cells; subsequently, the T cell response was assessed with the use of CD3/CD28 and interleukin (IL) 2. Cytokine production by ex vivo-stimulated naive cells and memory T cells was measured before and after oral supplementation with L. rhamnosus in 6 healthy volunteers and 6 patients with Crohn disease. RESULTS A decreased T cell proliferation and cytokine production, especially of IL-2, IL-4, and IL-10, was observed in CD3/CD28-stimulated T cells derived from L. rhamnosus-matured DCs. This T cell hyporesponsiveness was associated with enhanced DC-T cell interaction and normal responsiveness of T cells for IL-2. In vivo oral supplementation of L. rhamnosus for 2 wk induced a similar T cell hyporesponsiveness, including impaired ex vivo T helper subsets 1 and 2 responses without up-regulation of immunoregulatory cytokines in cohorts of both healthy volunteers and patients with Crohn disease. CONCLUSIONS We propose that L. rhamnosus modulates DC function to induce a novel form of T cell hyporesponsiveness; this mechanism might be an explanation for the observed beneficial effects of probiotic treatment in clinical disease.
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Affiliation(s)
- Henri Braat
- Laboratory of Experimental Internal Medicine and the Department of Gastroenterology, Academic Medical Center, Amsterdam, Netherlands.
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Abstract
The demonstration that immune and epithelial cells can discriminate between different microbial species has extended our understanding of the actions of probiotics beyond simple barrier and antimicrobial concepts. Several probiotic mechanisms of action, relative to inflammatory bowel disease, have been elucidated: (1) competitive exclusion, whereby probiotics compete with microbial pathogens for a limited number of receptors present on the surface epithelium; (2) immunomodulation and/or stimulation of an immune response of gut-associated lymphoid and epithelial cells; (3) antimicrobial activity and suppression of pathogen growth; (4) enhancement of barrier function; and (5) induction of T cell apoptosis in the mucosal immune compartment. The unraveling of these mechanisms of action has led to new support for the use of probiotics in the management of clinical inflammatory bowel disease. Though level 1 evidence now supports the therapeutic use of probiotics in the treatment of postoperative pouchitis, only levels 2 and 3 evidence is currently available in support of the use of probiotics in the treatment of ulcerative colitis and Crohn's disease. Nevertheless, one significant and consistent finding has emerged during the course of research in the past year: not all probiotic bacteria have similar therapeutic effects. Rigorously designed, controlled clinical trials are vital to investigate the unresolved issues related to efficacy, dose, duration of use, single or multi-strain formulation, and the concomitant use of probiotics, synbiotics, or antibiotics.
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Affiliation(s)
- Richard N Fedorak
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada.
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