RESUMO
Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperferritinemic systemic inflammatory disorders. Although profound cytotoxic impairment causes familial HLH (fHLH), the mechanisms driving non-fHLH and MAS are largely unknown. MAS occurs in patients with suspected rheumatic disease, but the mechanistic basis for its distinction is unclear. Recently, a syndrome of recurrent MAS with infantile enterocolitis caused by NLRC4 inflammasome hyperactivity highlighted the potential importance of interleukin-18 (IL-18). We tested this association in hyperferritinemic and autoinflammatory patients and found a dramatic correlation of MAS risk with chronic (sometimes lifelong) elevation of mature IL-18, particularly with IL-18 unbound by IL-18 binding protein, or free IL-18. In a mouse engineered to carry a disease-causing germ line NLRC4T337S mutation, we observed inflammasome-dependent, chronic IL-18 elevation. Surprisingly, this NLRC4T337S-induced systemic IL-18 elevation derived entirely from intestinal epithelia. NLRC4T337S intestines were histologically normal but showed increased epithelial turnover and upregulation of interferon-γ-induced genes. Assessing cellular and tissue expression, classical inflammasome components such as Il1b, Nlrp3, and Mefv predominated in neutrophils, whereas Nlrc4 and Il18 were distinctly epithelial. Demonstrating the importance of free IL-18, Il18 transgenic mice exhibited free IL-18 elevation and more severe experimental MAS. NLRC4T337S mice, whose free IL-18 levels were normal, did not. Thus, we describe a unique connection between MAS risk and chronic IL-18, identify epithelial inflammasome hyperactivity as a potential source, and demonstrate the pathogenicity of free IL-18. These data suggest an IL-18-driven pathway, complementary to the cytotoxic impairment of fHLH, with potential as a distinguishing biomarker and therapeutic target in MAS.
Assuntos
Interleucina-18/imunologia , Síndrome de Ativação Macrofágica/imunologia , Transdução de Sinais/imunologia , Substituição de Aminoácidos , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/imunologia , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/imunologia , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/imunologia , Humanos , Inflamassomos/genética , Inflamassomos/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Interleucina-18/genética , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/patologia , Síndrome de Ativação Macrofágica/genética , Síndrome de Ativação Macrofágica/patologia , Camundongos , Camundongos Knockout , Mutação de Sentido Incorreto , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Pirina/genética , Pirina/imunologia , Transdução de Sinais/genéticaRESUMO
OBJECTIVE: IL-18 is a pro-inflammatory cytokine of the IL-1 family that is naturally inhibited by IL-18 binding protein (IL-18BP). High levels of IL-18 have been described in the serum of adult-onset Still's disease (AOSD) patients, but only total IL-18 levels (including inactive IL-18 bound to IL-18BP) have been measured. With a specific immunoassay, we aimed to measure free IL-18 serum levels in AOSD patients and other rheumatic diseases. METHODS: An ELISA was developed to measure free IL-18. Its sensitivity and specificity were tested by spiking recombinant IL-18 or IL-18BP in serum and PBS supplemented with 5% BSA. The binding affinity of IL-18 to IL-18BP was calculated by titration experiments using the ELISA and by Biacore analysis. Sera of 37 AOSD patients and 138 controls (40 healthy controls, 30 RA, 29 SLE, 21 AS and 18 PsA) were assayed for free IL-18, IL-18BP, total IL-18 and other cytokines. Correlations were performed between free IL-18 and markers of disease activity in AOSD patients. RESULTS: Free IL-18 serum levels were significantly higher in AOSD patients (median 8.89 pg/ml) than in healthy and disease controls (1.37 pg/ml; P < 0.01). Free IL-18 serum levels correlated with AOSD activity. The affinity of IL-18 to IL-18BP was found to be much higher than previously described, with a dissociation constant ranging from 30 to 50 pM. CONCLUSION: Free IL-18 levels are specifically elevated in AOSD compared with other inflammatory diseases, suggesting that IL-18 represents a potential target for the treatment of AOSD.
Assuntos
Interleucina-18/metabolismo , Doença de Still de Início Tardio/sangue , Adulto , Idoso , Alanina Transaminase/metabolismo , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Ferritinas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Leucocitose/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ligação ProteicaRESUMO
To estimate the number of fallers and risk factors for falls in a cohort with dementia, we did a secondary analysis of a cluster-randomized controlled trial (NutriAlz) in 11 outpatient and day care centers in Catalonia (Spain) including 626 community-dwelling patients with dementia, followed for 12 months. Participants' characteristics were assessed at baseline, at 6 and 12 months [fall in the earlier 6 mo, anthropometric data, comorbidities, Mini-Mental State Examination, Clinical Dementia Rating, Basic Activities of Daily Living (BADL), Instrumental Activities of Daily Living, Neuropsychiatric Inventory Questionnaire, Zarit Caregiver Burden Interview and Mini-Nutritional Assessment]. Multivariate logistic regression models and generalized linear models were used to explore risk factors for falls and changes in health and function. Two hundred twenty-three participants fell during the 12 months follow-up (35.62%). Risk factors identified for falls were age (odds ratio (OR)=1.03, 95% confidence interval (CI), 1.00-1.05), BADL (OR=1.18, 95% CI, 1.05-1.32), and earlier fall (OR=2.30, 95% CI, 1.57-3.35). Fallers had worse health than nonfallers, and their dependence increased significantly more in BADL during the study, compared with nonfallers. Dependence in BADL is a risk factor and a consequence of falls; interventions aimed at preventing falls in dementia patients could promote autonomy in BADL and slow its decline.
Assuntos
Acidentes por Quedas/prevenção & controle , Acidentes por Quedas/estatística & dados numéricos , Demência , Atividades Cotidianas/psicologia , Doença de Alzheimer , Estudos de Coortes , Demência/diagnóstico , Demência/etiologia , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Características de Residência , Fatores de Risco , Espanha , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: The aim of this study was to demonstrate the tolerance and safety of an enteral formula containing prebiotics/probiotics, and its effect on the faecal microbiota in critically ill children. SUBJECTS AND METHODS: Ninety-four patients between 1 and 3 years old under mechanical ventilation requiring enteral feeding were randomised to receive either a test formula containing a synbiotic blend (composed of 2 probiotic strains [Lactobacillus paracasei NCC 2461 and Bifidobacterium longum NCC 3001], fructooligosaccharides [FOS], inulin, and Acacia gum), or a control formula. Patients remained in the intensive care unit for 7 days and were examined at day 14. Tolerance was assessed by overall caloric intake and time to reach caloric goal. Safety was assessed by abdominal distention, vomiting, and stool frequency. Microbiota was analysed by culture- and molecular-based methods. RESULTS: Overall caloric intake and time to reach caloric goal were similar between groups (noninferiority was shown). Abdominal distention, vomiting, and stool frequency were not affected by the supplementation with pre- and probiotics. Faecal bifidobacteria were higher in the test group at the end of the study. A similar trend was observed for total lactobacilli. L paracasei NCC 2461 and B longum NCC 3001 were detected in 80.4% and 17% of the test group patients, respectively. Enterobacteria levels remained unchanged during hospitalisation in the control group but diminished in the test group. CONCLUSIONS: The enteral formula supplemented with synbiotics was well tolerated by children in intensive care units; it was safe and produced an increase in faecal bacterial groups of previously reported beneficial effects.
Assuntos
Nutrição Enteral , Fezes/microbiologia , Alimentos Formulados/efeitos adversos , Homeostase , Prebióticos/efeitos adversos , Probióticos/efeitos adversos , Dor Abdominal/epidemiologia , Bifidobacterium/isolamento & purificação , Pré-Escolar , Diarreia/epidemiologia , Método Duplo-Cego , Ingestão de Energia , Enterococcaceae/isolamento & purificação , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Lactobacillus/isolamento & purificação , Masculino , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Vômito/epidemiologiaRESUMO
A common finding in the elderly population is a chronic subclinical inflammatory status that coexists with immune dysfunction. These interconnected processes are of sufficient magnitude to impact health and survival time. In this review we discuss the different signals that may stimulate the inflammatory process in the aging population as well as the molecular and cellular components that can participate in the initiation, the modulation or termination of the said process. A special interest has been devoted to the intestine as a source of signals that can amplify local and systemic inflammation. Sentinel cells in the splanchnic area are normally exposed to more than one stimulus at a given time. In the intestine of the elderly, endogenous molecules produced by the cellular aging process and stress as well as exogenous evolutionarily conserved molecules from bacteria, are integrated into a network of receptors and molecular signalling pathways that result in chronic inflammatory activation. It is thus possible that nutritional interventions which modify the intestinal ecology can diminish the pro-inflammatory effects of the microbiota and thereby reinforce the mucosal barrier or modulate the cellular activation pathways.
Assuntos
Inflamação/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Intestinos/imunologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Humanos , Imunidade Celular , Inflamação/microbiologia , Inflamação/prevenção & controle , Mediadores da Inflamação/metabolismo , Metagenoma , Probióticos/farmacologiaRESUMO
A study was conducted in healthy elderly living independently in senior housing to assess the impact of a probiotic yoghurt supplement on small intestinal bacterial overgrowth. Twenty-three participants with positive and thirteen participants with negative hydrogen breath test were studied before and after a period of 4 weeks of probiotic yoghurt administration. Intestinal permeability, plasma endotoxin levels, phagocytic activity of leucocytes, cytokine production by monocytes and free radical response of neutrophils were determined. Intestinal permeability was similar for the two groups and was unaffected by probiotic treatment. Both plasma endotoxin levels and the basal phagocytic activity of leucocytes decreased after yoghurt intake in the two groups. Exposure of monocytes and neutrophils ex vivo led to an increased cytokine response and free radical response, respectively. The normalisation of the various cytokine responses was more apparent in the group with positive breath test. In addition, the plasma levels of lipoplysaccharide binding protein and soluble CD14, lipoplysaccharide pattern recognition receptors and surrogate markers of lipoplysaccharide permeability were diminished by the end of the study. In conclusion, probiotic administration in the elderly normalises the response to endotoxin, and modulates activation markers in blood phagocytes, and therefore may help reduce low-grade chronic inflammation.
Assuntos
Infecções Bacterianas/dietoterapia , Ileíte/dietoterapia , Mucosa Intestinal/microbiologia , Intestino Delgado , Probióticos/administração & dosagem , Iogurte , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/diagnóstico , Translocação Bacteriana , Testes Respiratórios , Estudos de Casos e Controles , Citocinas/metabolismo , Endotoxemia/dietoterapia , Feminino , Seguimentos , Humanos , Ileíte/diagnóstico , Ileíte/microbiologia , Absorção Intestinal , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Fagocitose , Espécies Reativas de Oxigênio/análise , Estatísticas não ParamétricasRESUMO
Fructooligosaccharides (FOS) are considered prebiotics because of their ability to promote growth of specific beneficial gut bacteria, such as bifidobacteria. Some studies reported potential immune-modulating properties. The aim of this study was to investigate the effect of FOS:inulin mix on murine response to Salmonella vaccine and evaluate the relevance toward protection against Salmonella infection. Balb/c mice were fed a diet containing 5% FOS:inulin mix or a control diet 1 wk before oral immunization with a suboptimal dose of live attenuated Salmonella typhimurium vaccine. Four weeks after vaccination, mice were infected with LD100 of virulent S. typhimurium. Specific blood Salmonella immunoglobulin G and fecal immunoglobulin A significantly increased in mice fed the diet containing prebiotics compared with control mice 4 wk postimmunization. Peritoneal macrophage phagocytic activity also significantly increased in FOS:inulin-fed mice at 1 wk postimmunization compared with control mice. No detectable effects were observed on the percentage of lymphoid cell subsets in the spleen. However, production of cytokines, interferon-gamma, interleukin-12, and tumor necrosis factor alpha, was numerically increased in spleen cell cultures stimulated with mitogens from FOS:inulin-fed mice 1 and 4 wk postimmunization. Salmonella translocation to lymphoid organs was not affected by feeding FOS:inulin. However, the improved response to Salmonella vaccine was concomitant with an increase in the survival rate of FOS:inulin-fed mice upon challenge with virulent Salmonella. No detectable effects were observed on the composition or the metabolic activity of the microbiota. Overall, the data suggest that a diet supplemented with FOS:inulin mix stimulates mucosal immunity and seems to improve efficacy of an oral vaccine.
Assuntos
Dieta , Inulina/administração & dosagem , Oligossacarídeos/administração & dosagem , Vacinas contra Salmonella/imunologia , Administração Oral , Animais , Anticorpos Antibacterianos , Citocinas/metabolismo , Feminino , Imunoglobulina A/metabolismo , Imunoglobulina G/sangue , Inulina/farmacologia , Metaloporfirinas , Camundongos , Camundongos Endogâmicos BALB C , Oligossacarídeos/farmacologia , Fagócitos , Infecções por Salmonella/prevenção & controle , Vacinas contra Salmonella/administração & dosagem , Baço/citologia , Baço/metabolismoAssuntos
Antioxidantes/farmacologia , Translocação Bacteriana/efeitos dos fármacos , Lactobacillus , Cirrose Hepática Experimental/microbiologia , Probióticos/farmacologia , Animais , Tetracloreto de Carbono/toxicidade , Cirrose Hepática Experimental/induzido quimicamente , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: A casein-based formula containing TGF-beta has been successfully used in adolescents during acute episodes of Crohn's disease. The role played by this molecule requires confirmation. We have examined the capacity of a TGF-beta containing diet to control the intestinal inflammation in HLA-B27 transgenic rats, and compared its effects with a similar diet devoid of TGF-beta. METHODS: Three groups of rats were studied. HLA-B27/hbeta2M transgenic rats were fed with a casein-based rat-adapted diet containing TGF-beta or a control casein-based diet without TGF-beta. Fischer control animals were fed the latter. Body weight, dietary intake, tissue weights, fecal samples, leukocyte counts, and acute phase response were analyzed. Intestinal inflammation was assessed by histology, myeloperoxidase, and mRNA expression of cytokines. MUC2 protein expression was assessed by immunohistochemistry. Breakdown of muscle protein was examined. RESULTS: The test diet improved diarrhea increasing the fecal dry matter and the colonic inflammation as shown by a lower inflammatory score (2.43 +/- 1.13 vs 4.42 +/- 0.53, p < .05), lower mucosal thickness (431.25 +/- 72.29 vs 508.57 +/- 81.32 microm, p = .08) and decreased IFNgamma mRNA expression. MUC2 protein expression was increased in HLA rats fed the TGF-beta diet compared with HLA rats fed the control diet, but restitution to normal pattern was not observed. The test diet also decreased leukocytosis and the acute phase response and improved the muscle catabolic response. CONCLUSION: The TGF-beta containing diet has a beneficial effect in an animal model of intestinal inflammation. Our observations support a potential role for dietary TGF-beta in the restoration of immune homeostasis.
Assuntos
Animais Geneticamente Modificados , Doença de Crohn/terapia , Nutrição Enteral , Antígeno HLA-B27/genética , Fator de Crescimento Transformador beta/uso terapêutico , Reação de Fase Aguda , Animais , Peso Corporal/efeitos dos fármacos , Caseínas , Modelos Animais de Doenças , Imuno-Histoquímica , Mucina-2 , Mucinas/metabolismo , Músculo Esquelético/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Endogâmicos F344 , Resultado do TratamentoRESUMO
The intestinal mucosa is unique in that it can be tolerant to the resident, symbiotic microbiota but remaining, at the same time, responsive to and able to fight pathogens. The close interaction between host-symbiotic microbiota at the mucosal level poses important challenges since microbial breaches through the gut barrier can result in the breakdown of gut homeostasis. In this paper, hosts-integrated components that help to preserve intestinal homeostasis including barrier and immune function are discussed. In addition global alterations of the microbiota that can play a role in the initiation of an exaggerated inflammatory response through an abnormal signaling of the innate and adaptive immune response are briefly described.
RESUMO
Mucosal dendritic cells are at the heart of decision-making processes that dictate immune reactivity to intestinal microbes. They ensure tolerance to commensal bacteria and a vigorous immune response to pathogens. It has recently been demonstrated that the former involves a limited migration of bacterially loaded dendritic cells from the Peyer's patches to the mesenteric lymph nodes. During lactation, cells from gut-associated lymphoid tissue travel to the breast via the lymphatics and peripheral blood. Here, we show that human peripheral blood mononuclear cells and breast milk cells contain bacteria and their genetic material during lactation. Furthermore, we show an increased bacterial translocation from the mouse gut during pregnancy and lactation and the presence of bacterially loaded dendritic cells in lactating breast tissue. Our observations show bacterial translocation as a unique physiological event, which is increased during pregnancy and lactation. They suggest endogenous transport of intestinally derived bacterial components within dendritic cells destined for the lactating mammary gland. They also suggest neonatal immune imprinting by milk cells containing commensal-associated molecular patterns.
Assuntos
Translocação Bacteriana , Aleitamento Materno , Células Dendríticas/fisiologia , Sistema Imunitário/crescimento & desenvolvimento , Recém-Nascido , Mucosa Intestinal/microbiologia , Leite Humano/imunologia , Adulto , Animais , Bactérias/genética , Sangue/microbiologia , Movimento Celular , Feminino , Humanos , Sistema Imunitário/microbiologia , Mucosa Intestinal/imunologia , Lactação/fisiologia , Leucócitos Mononucleares/microbiologia , Linfa/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Leite Humano/microbiologia , GravidezRESUMO
PURPOSE OF REVIEW: Recent studies suggest an association between inflammation status and the presence of chronic disease in the elderly. The review examines publications that address the low level of chronic inflammation and emphasizes how an altered host-microbiota interaction at the gut level could contribute to maintaining a low systemic inflammatory status in the elderly. RECENT FINDINGS: The first population cross-sectional studies with relevant numbers of healthy elderlies show age-related global changes in gut microbiota with a consistent increase in nonpathogenic Gram-negative mainly Enterobacteria and country-specific changes in bifidobacteria. Noninvasive methods have permitted us to detect subclinical intestinal inflammation in the elderly population. Furthermore, few studies report on immune and/or inflammatory response; however, prebiotics, probiotics or synbiotics might improve the inflammatory condition of the elderly. SUMMARY: A better understanding of the mechanisms of host-gut microbiota cross-talk would significantly help in the design of novel nutritional strategies targeting immune reactivity at the mucosal level.
Assuntos
Envelhecimento/imunologia , Bactérias/crescimento & desenvolvimento , Trato Gastrointestinal/microbiologia , Imunidade nas Mucosas , Inflamação/prevenção & controle , Probióticos , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Doença Crônica , Fenômenos Fisiológicos do Sistema Digestório , Humanos , Probióticos/administração & dosagem , Probióticos/uso terapêuticoRESUMO
OBJECTIVE: We examined the presence of a natural bacterial inoculum in breast milk and its intracellular transport from the maternal intestine to the breast through the circulation. METHODS: Breast milk and peripheral blood were collected aseptically from healthy donors at various times after delivery, and the presence of viable bacteria was determined through plating. Temporal temperature gradient gel electrophoresis was used to examine the bacterial ribosomal DNA content in milk cells, maternal peripheral blood mononuclear cells, and feces and in corresponding infant feces. Blood from nongravid nonlactating women served as control samples. Bacterial translocation to extraintestinal tissues was also evaluated in virgin, pregnant, and lactating mice. RESULTS: Breast milk contained a low total concentration of microbes of <10(3) colony-forming units per mL. Temporal temperature gradient gel electrophoresis revealed that maternal blood and milk cells contained the genetic material of a greater biodiversity of enteric bacteria. Some bacterial signatures were common to infant feces and to samples of maternal origin. Bacterial translocation from the gut to mesenteric lymph nodes and mammary gland occurred during late pregnancy and lactation in mice. CONCLUSIONS: Bacterial translocation is a unique physiologic event, which is increased during pregnancy and lactation in rodents. Human breast milk cells contain a limited number of viable bacteria but a range of bacterial DNA signatures, as also found in maternal peripheral blood mononuclear cells. Those peripheral blood mononuclear cells showed greater biodiversity than did peripheral blood mononuclear cells from control women. Taken together, our results suggest that intestinally derived bacterial components are transported to the lactating breast within mononuclear cells. We speculate that this programs the neonatal immune system to recognize specific bacterial molecular patterns and to respond appropriately to pathogens and commensal organisms.
Assuntos
Translocação Bacteriana/fisiologia , Recém-Nascido/imunologia , Lactação/fisiologia , Leite Humano/microbiologia , Animais , Sangue/microbiologia , Fezes/microbiologia , Feminino , Humanos , Intestinos/microbiologia , Camundongos , Modelos Animais , Gravidez , Valores de ReferênciaRESUMO
This study describes the in vivo activity of Lactobacillus johnsonii La1 (NCC533) in Giardia intestinalis-infected gerbils (Meriones unguiculatus). Daily administration of lactobacilli in the drinking water from 7 days before inoculation with Giardia trophozoites efficiently prevented G. intestinalis strain WB clone C6 from infecting gerbils. More specifically, shedding of fecal Giardia antigens (GSA65 protein) was diminished in the La1-treated group, and resolution of infection was observed by 21 days postinoculation. Histology and analysis of enzymatic markers of microvillus membrane integrity revealed that probiotic administration also protected against parasite-induced mucosal damage. In addition, a cellular response to Giardia antigens was stimulated in spleen cells from La1-treated gerbils. Results show for the first time the antigiardial effect of probiotic lactobacilli in vivo and provide further insight into the antagonistic properties of lactic acid bacteria against protozoa involved in intestinal infections.
Assuntos
Antígenos de Protozoários/imunologia , Giardia lamblia/metabolismo , Giardíase/prevenção & controle , Lactobacillus/metabolismo , Animais , Gerbillinae , Giardíase/imunologia , Giardíase/microbiologiaRESUMO
The intestinal microflora can be considered a postnatally acquired organ that is composed of a large diversity of bacteria that perform important functions for the host and can be modulated by environmental factors, such as nutrition. Specific components of the intestinal microflora, including lactobacilli and bifidobacteria, have been associated with beneficial effects on the host, such as promotion of gut maturation and integrity, antagonisms against pathogens and immune modulation. Beyond this, the microflora seems to play a significant role in the maintenance of intestinal immune homeostasis and prevention of inflammation. The contribution of the intestinal epithelial cell in the first line of defense against pathogenic bacteria and microbial antigens has been recognized. However, the interactions of intestinal epithelial cells with indigenous bacteria are less well understood. This review will summarize the increasing scientific attention to mechanisms of the innate immune response of the host towards different components of the microflora, and suggest a potential role for selected probiotic bacteria in the regulation of intestinal inflammation.
Assuntos
Imunidade nas Mucosas , Intestinos/imunologia , Intestinos/microbiologia , Probióticos , Animais , Bactérias/imunologia , Homeostase , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Mucosa Intestinal/imunologia , Modelos Imunológicos , Probióticos/uso terapêuticoRESUMO
Lactobacilli derived from the endogenous flora of normal donors are being increasingly used as probiotics in functional foods and as vaccine carriers. However, a variety of studies done with distinct strains of lactobacilli has suggested heterogeneous and strain-specific effects. To dissect this heterogeneity at the immunological level, we selected two strains of lactobacilli that displayed similar properties in vitro and studied their impact on mucosal and systemic B-cell responses in monoxenic mice. Germfree mice were colonized with Lactobacillus johnsonii (NCC 533) or Lactobacillus paracasei (NCC 2461). Bacterial loads were monitored for 30 days in intestinal tissues, and mucosal and systemic B-cell responses were measured. Although both Lactobacillus strains displayed similar growth, survival, and adherence properties in vitro, they colonized the intestinal lumen and translocated into mucosal lymphoid organs at different densities. L. johnsonii colonized the intestine very efficiently at high levels, whereas the number of L. paracasei decreased rapidly and it colonized at low levels. We determined whether this difference in colonization correlated with an induction of different types of immune responses. We observed that colonization with either strain induced similar germinal center formation and immunoglobulin A-bearing lymphocytes in the mucosa, suggesting that both strains were able to activate mucosal B-cell responses. However, clear differences in patterns of immunoglobulins were observed between the two strains in the mucosa and in the periphery. Therefore, despite similar in vitro probiotic properties, distinct Lactobacillus strains may colonize the gut differently and generate divergent immune responses.
Assuntos
Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Lactobacillus/crescimento & desenvolvimento , Lactobacillus/imunologia , Probióticos/administração & dosagem , Animais , Linfócitos B/imunologia , Aderência Bacteriana , Células CACO-2 , Feminino , Vida Livre de Germes , Humanos , Imunoglobulina A Secretora/metabolismo , Camundongos , Camundongos Endogâmicos C3H , Especificidade da EspécieRESUMO
The gut microflora play a crucial role in several physiologic functions of the host, including maturation of the gut-associated lymphoid tissues during the first months of life. Oral administration of probiotic lactic acid bacteria (LAB) modulates the immune system of humans and some laboratory animals. This effect has never been examined in dogs; therefore, our aim was to study the capacity of a probiotic LAB to stimulate immune functions in young dogs. Puppies were allotted to two groups receiving either a control diet or a diet supplemented with 5 x 10(8) colony forming units (cfu)/d of probiotic Enterococcus faecium (SF68) from weaning to 1 y of age. Fecal and blood samples were collected from the dogs at different time points for the measurement of fecal immunoglobulin (Ig)A, circulating IgG and IgA, and the proportions of lymphoid cell subsets. Fecal IgA and canine distemper virus (CDV) vaccine-specific circulating IgG and IgA were higher in the group receiving the probiotic than in controls. There were no differences in the percentages of CD4(+) and CD8(+) T cells between the groups, but the proportion of mature B cells [CD21(+)/major histocompatibility complex (MHC) class II(+)] was greater in those fed the probiotic. These data show for the first time that a dietary probiotic LAB enhance specific immune functions in young dogs, thus offering new opportunities for the utilization of probiotics in canine nutrition.
Assuntos
Ração Animal/microbiologia , Formação de Anticorpos , Cães/imunologia , Enterococcus faecium , Imunidade Celular , Animais , Separação Celular , Feminino , Citometria de Fluxo , MasculinoRESUMO
BACKGROUND/AIMS: Probiotics and antioxidants could be alternatives to antibiotics in the prevention of bacterial infections in cirrhosis. The aim of the present study was to determine the effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora, endotoxemia, and bacterial translocation in cirrhotic rats. METHODS: Twenty-nine Sprague-Dawley rats with cirrhosis induced by CCl(4) and ascites received Lactobacillus johnsonii La1 10(9)cfu/day in vehicle (antioxidants: vitamin C+glutamate) (n=10), vehicle alone (n=11), or water (n=8) by gavage. Another eight non-cirrhotic rats formed the control group. After 10 days of treatment, a laparotomy was performed to determine microbiological study of ileal and cecal feces, bacterial translocation, endotoxemia, and intestinal malondialdehyde (MDA) levels as index of intestinal oxidative damage. RESULTS: Intestinal enterobacteria and enterococci, bacterial translocation (0/11 and 0/10 vs. 5/8, P<0.01), and ileal MDA levels (P<0.01) were lower in cirrhotic rats treated with antioxidants alone or in combination with Lactobacillus johnsonii La1 compared to cirrhotic rats receiving water. Only rats treated with antioxidants and Lactobacillus johnsonii La1 showed a decrease in endotoxemia with respect to cirrhotic rats receiving water (P<0.05). CONCLUSIONS: Antioxidants alone or in combination with Lactobacillus johnsonii La1 can be useful in preventing bacterial translocation in cirrhosis.