Cholinergic immunomodulation in inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are chronic intestinal disorders characterized by dysregulated immune responses to resident microbiota in genetically susceptible hosts. The activation of the cholinergic system has been proposed for the treatment of IBD patients according to its potential anti-inflammatory effect in vivo. The α-7-nicotinic-acetylcholine receptor (α7nAChR) is involved in the inhibition of inflammatory processes, modulating the production of cytokines, suppressing dendritic cells and macrophage activity, leading to the suppression of T cells. In this review, we address the most recent studies and clinical trials concerning cholinergic signaling and its therapeutic potential for inflammatory bowel diseases.

Environmental rearing conditions are key determinants of changes in immune gene expression patterns in shrimp midgut.

The super-intensive BioFloc Technology (BFT) system has been highlighted as a promising eco-friendly alternative to the traditional shrimp rearing systems. To gain insight into the impact of environmental rearing conditions on shrimp intestinal immunity, we assessed the expression profile of key immunological genes in the midgut of Litopenaeus vannamei shrimp reared in two contrasting culture systems: the indoor super-intensive BFT and the outdoor intensive Green-Water System (GWS). From the 30 analyzed genes, the expression levels of 25 genes were higher in the midgut of shrimp reared in BFT than in GWS. The main functional categories represented in BFT-shrimp were the prophenoloxidase-activating system, immune signaling, antimicrobial peptides, and RNA interference pathway. Comparatively, only the RNAi pathway gene Dicer-1 (LvDcr1) was more expressed in animals from the GWS group. However, despite the differences in gene expression, the total midgut bacterial abundance was similar between the experimental groups. Altogether, our results suggest that the microbial-rich environment offered by the BFT system can be acting as an immunostimulant by altering the immune expression profile of the midgut. The gene expression level found in GWS animals could be related to the chronic presence of the IMNV in the Brazilian Northeast. Knowing the effects of environmental stress factors on the intestinal immune defenses can provide an in-depth understanding of the relationship between cultivated shrimp and the major pathogens affecting the shrimp industry.

Evaluation of the Immunomodulatory Activities of the Probiotic Strain Lactobacillus fermentum UCO-979C.

Lactobacillus fermentum UCO-979C, a strain isolated from a human stomach, was previously characterized by its potential probiotic properties. The UCO-979C strain displayed the ability to beneficially regulate the innate immune response triggered by Helicobacter pylori infection in human gastric epithelial cells. In this work, we conducted further in vitro studies in intestinal epithelial cells (IECs) and in vivo experiments in mice in order to characterize the potential immunomodulatory effects of L. fermentum UCO-979C on the intestinal mucosa. Results demonstrated that the UCO-979C strain is capable to differentially modulate the immune response of IECs triggered by Toll-like receptor 4 (TLR4) activation through the modulation of TLR negative regulators' expression. In addition, we demonstrated for the first time that L. fermentum UCO-979C is able to exert its immunomodulatory effect in the intestinal mucosa in vivo. The feeding of mice with L. fermentum UCO-979C significantly increased the production of intestinal IFN-γ, stimulated intestinal and peritoneal macrophages and increased the number of Peyer's patches CD4+ T cells. In addition, L. fermentum UCO-979C augmented intestinal IL-6, reduced the number of immature B220+CD24high B cells from Peyer's patches, enhanced the number of mature B B220+CD24low cells, and significantly increased intestinal IgA content. The results of this work revealed that L. fermentum UCO-979C has several characteristics making it an excellent candidate for the development of immunobiotic functional foods aimed to differentially regulate immune responses against gastric and intestinal pathogens.

Potential immunomodulatory and protective effects of the Arthrospira-based dietary supplement on shrimp intestinal immune defenses.

Herein, we evaluated the immunomodulatory and the antiviral protective properties of a cyanobacteria-enriched diet on the immune responses of the Pacific white shrimp Litopenaeus vannamei challenged with the White spot syndrome virus (WSSV). Shrimp were fed with an Arthrospira platensis supplemented feed during 20 days, and its effects were examined by evaluating well-known standardized shrimp immune parameters (total hemocyte counts, total protein concentration, phenoloxidase activity, and serum agglutination titer). Additionally, we assessed the expression of crucial genes involved in both hemolymph- and gut-based immunities related to the shrimp capacity to circumvent viral and microbial infections. Dietary supplementation improved shrimp survival rates after challenge with a median lethal dose of WSSV. From all immune parameters tested, only the serum agglutination titer was higher in treated animals. On the other hand, the expression of some representative marker genes from different immune response pathways was only modulated in the midgut and not in the circulating hemocytes, suggesting that this feed supplementation can be used as an attractive strategy to enhance immunity in shrimp gut. Altogether, our results evidence the immunomodulatory properties of A. platensis supplemented feed in shrimp humoral and intestinal defenses and highlight the potential use of cyanobacteria-based immunostimulants in shrimp farming for protection against infectious diseases.

Microbiota intestinal y salud infantil / Intestinal microbiota and child health

Introducción: la microbiota intestinal participa en eventos de homeostasis e inmunidad intestinal de trascendencia para la salud humana. Sus interacciones con el ecosistema intestinal, participación en distintas enfermedades, y el valor de los probióticos y prebióticos son revisados. Objetivo: evaluar los conocimientos de la literatura médica en las últimas décadas sobre los principales aspectos de la microbiota intestinal, su relación con la inmunidad, y beneficios de probióticos y prebióticos como terapia en distintas afecciones intestinales y extraintestinales. Métodos: se realiza búsqueda en bases de datos de PubMed, Scielo, Redalycs, Latindex de publicaciones acerca de microbiota intestinal, revisiones sistemáticas de probióticos y libros afines. Desarrollo: se revisan las características de los procesos de colonización, desarrollo, funciones y composición de la microbiota intestinal, su inmunidad y relación con el hígado. Se actualizan los principios de la terapia con probióticos y prebióticos, y sus distintas indicaciones en enfermedades digestivas. Conclusiones finales: se evidencia el papel del microbioma intestinal y su relación con el ecosistema intestinal, los mecanismos participantes y el consiguiente desarrollo de su inmunidad, resaltando el rol de la lactancia materna para un adecuado proceso de implantación de la microbiota. Se analiza el uso de probióticos y prebióticos, y su eficacia en distintas enfermedades digestivas(AU)

Introduction: the intestinal microbiota is involved in homeostasis and intestinal immunity events which are crucial to human health. An overview is provided of its interactions with the intestinal ecosystem, its participation in various conditions, and the value of probiotics and prebiotics. Objective: evaluate the information contained in the medical literature published in the past decades about the main features of the intestinal microbiota, its relationship to immunity, and the beneficial therapeutic action of probiotics and prebiotics in various intestinal and extra-intestinal disorders. Methods: a search was conducted in the databases PubMed, SciELO, Redalyc and Latindex for publications about the intestinal microbiota, systematic reviews about probiotics, and related books. Results: examination was carried out of the characteristics of colonization processes, development, functions and composition of the intestinal microbiota, as well as its immunity and relationship to the liver. Updating was also performed about the principles underlying the therapy with probiotics and prebiotics, and their various indications for digestive diseases. Final conclusions: a description is provided of the role of the intestinal microbiota and its relationship to the intestinal ecosystem, the mechanisms involved and the consequent development of its immunity, pointing out the role of breastfeeding for an adequate process of implantation of the microbiota. An analysis is made of the use of probiotics and prebiotics, and their efficacy for various digestive diseases(AU)

Microbiota intestinal y salud infantil / Intestinal microbiota and child health

Introducción: la microbiota intestinal participa en eventos de homeostasis e inmunidad intestinal de trascendencia para la salud humana. Sus interacciones con el ecosistema intestinal, participación en distintas enfermedades, y el valor de los probióticos y prebióticos son revisados. Objetivo: evaluar los conocimientos de la literatura médica en las últimas décadas sobre los principales aspectos de la microbiota intestinal, su relación con la inmunidad, y beneficios de probióticos y prebióticos como terapia en distintas afecciones intestinales y extraintestinales. Métodos: se realiza búsqueda en bases de datos de PubMed, Scielo, Redalycs, Latindex de publicaciones acerca de microbiota intestinal, revisiones sistemáticas de probióticos y libros afines. Desarrollo: se revisan las características de los procesos de colonización, desarrollo, funciones y composición de la microbiota intestinal, su inmunidad y relación con el hígado. Se actualizan los principios de la terapia con probióticos y prebióticos, y sus distintas indicaciones en enfermedades digestivas. Conclusiones finales: se evidencia el papel del microbioma intestinal y su relación con el ecosistema intestinal, los mecanismos participantes y el consiguiente desarrollo de su inmunidad, resaltando el rol de la lactancia materna para un adecuado proceso de implantación de la microbiota. Se analiza el uso de probióticos y prebióticos, y su eficacia en distintas enfermedades digestivas(AU)

Introduction: the intestinal microbiota is involved in homeostasis and intestinal immunity events which are crucial to human health. An overview is provided of its interactions with the intestinal ecosystem, its participation in various conditions, and the value of probiotics and prebiotics. Objective: evaluate the information contained in the medical literature published in the past decades about the main features of the intestinal microbiota, its relationship to immunity, and the beneficial therapeutic action of probiotics and prebiotics in various intestinal and extra-intestinal disorders. Methods: a search was conducted in the databases PubMed, SciELO, Redalyc and Latindex for publications about the intestinal microbiota, systematic reviews about probiotics, and related books. Results: examination was carried out of the characteristics of colonization processes, development, functions and composition of the intestinal microbiota, as well as its immunity and relationship to the liver. Updating was also performed about the principles underlying the therapy with probiotics and prebiotics, and their various indications for digestive diseases. Final conclusions: a description is provided of the role of the intestinal microbiota and its relationship to the intestinal ecosystem, the mechanisms involved and the consequent development of its immunity, pointing out the role of breastfeeding for an adequate process of implantation of the microbiota. An analysis is made of the use of probiotics and prebiotics, and their efficacy for various digestive diseases(AU)

An immune-related gene expression atlas of the shrimp digestive system in response to two major pathogens brings insights into the involvement of hemocytes in gut immunity.

Much of our current knowledge on shrimp immune system is restricted to the defense reactions mediated by the hemocytes and little is known about gut immunity. Here, we have investigated the transcriptional profile of immune-related genes in different organs of the digestive system of the shrimp Litopenaeus vannamei. First, the tissue distribution of 52 well-known immune-related genes has been assessed by semiquantitative analysis in the gastrointestinal tract (foregut, midgut and hindgut) and in the hepatopancreas and circulating hemocytes of shrimp stimulated or not with heat-killed bacteria. Then, the expression levels of 18 genes from key immune functional categories were quantified by fluorescence-based quantitative PCR in the midgut of animals experimentally infected with the Gram-negative Vibrio harveyi or the White spot syndrome virus (WSSV). Whereas the expression of some genes was induced at 48 h after the bacterial infection, any of the analyzed genes showed to be modulated in response to the virus. Whole-mount immunofluorescence assays confirmed the presence of infiltrating hemocytes in the intestines, indicating that the expression of some immune-related genes in gut is probably due to the migratory behavior of these circulating cells. This evidence suggests the participation of hemocytes in the delivery of antimicrobial molecules into different portions of the digestive system. Taken all together, our results revealed that gut is an important immune organ in L. vannamei with intimate association with hemocytes.

Inactivated polio vaccines from three different manufacturers have equivalent safety and immunogenicity when given as 1 or 2 additional doses after bivalent OPV: Results from a randomized controlled trial in Latin America.

BACKGROUND: Since April 2016 inactivated poliovirus vaccine (IPV) has been the only routine source of polio type 2 protection worldwide. With IPV supply constraints, data on comparability of immunogenicity and safety will be important to optimally utilize available supplies from different manufacturers. METHODS: In this multicenter phase IV study, 900 Latin American infants randomly assigned to six study groups received three doses of bOPV at 6, 10 and 14weeks and either one IPV dose at 14weeks (groups SP-1, GSK-1 and BBio-1) or two IPV doses at 14 and 36weeks (groups SP-2, GSK-2 and BBio-2) from three different manufacturers. Children were challenged with mOPV2 at either 18 (one IPV dose) or 40weeks (two IPV doses) and stools were collected weekly for 4weeks to assess viral shedding. Serum neutralizing antibodies were measured at various time points pre and post vaccination. Serious adverse events and important medical events (SAE and IME) were monitored for 6months after last study vaccine. RESULTS: At week 18, 4weeks after one dose of IPV, overall type 2 seroconversion rates were 80.4%, 80.4% and 73.3% for SP-1, GSK-1 and BBio-1 groups, respectively; and 92.6%, 96.8% and 88.0% in those who were seronegative before IPV administration. At 40weeks, 4weeks after a second IPV dose, type 2 seroconversion rates were ≥99% for any of the three manufacturers. There were no significant differences in fecal shedding index endpoint (SIE) after one or two IPV doses (SP: 2.3 [95% CI: 2.1-2.6]); GSK: 2.2 [1.7-2.5]; BBio 1.8 [1.5-2.3]. All vaccines appeared safe, with no vaccine-related SAE or IME. CONCLUSION: Current WHO prequalified IPV vaccines are safe and induce similar humoral and intestinal immunity after one or two doses. The parent study was registered with ClinicalTrials.gov, number NCT01831050.

Regulation of toll-like receptors-mediated inflammation by immunobiotics in bovine intestinal epitheliocytes: role of signaling pathways and negative regulators.

Intestinal epithelial cells (IECs) detect bacterial and viral associated molecular patterns via germline-encoded pattern-recognition receptors (PRRs) and are responsible for maintaining immune tolerance to the communities of resident commensal bacteria while being also capable to mount immune responses against pathogens. Toll-like receptors (TLRs) are a major class of PRRs expressed on IECs and immune cells, which are involved in the induction of both tolerance and inflammation. In the last decade, experimental and clinical evidence was generated to support the application of probiotics with immunoregulatory capacities (immunobiotics) for the prevention and treatment of several gastrointestinal inflammatory disorders in which TLRs exert a significant role. The majority of these studies were performed in mouse and human cell lines, and despite the growing interest in the bovine immune system due to the economic importance of cattle as livestock, only few studies have been conducted on cattle. In this regard, our group has established a bovine intestinal epithelial (BIE) cell line originally derived from fetal bovine intestinal epitheliocytes and used this cell line to evaluate the impact of immunobiotics in TLR-mediated inflammation. This review aims to summarize the current knowledge of the beneficial effects of immunobiotics in the regulation of intestinal inflammation/infection in cattle. Especially, we discuss the role of TLRs and their negative regulators in both the inflammatory response and the beneficial effects of immunobiotics in bovine IECs. This review article emphasizes the cellular and molecular interactions of immunobiotics with BIE cells through TLRs and gives the scientific basis for the development of immunomodulatory feed for bovine healthy development.

Modulation of Intestinal TLR4-Inflammatory Signaling Pathways by Probiotic Microorganisms: Lessons Learned from Lactobacillus jensenii TL2937.

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.

El fenomeno de la tolerancia oral / Oral tolerance phenomenon

Se da el nombre de tolerancia oral al estado de respuesta inmune sistemica disminuida a antigenos, administrados por via oral. Si bien el fenomeno fue descrito anecdoticamente desde hace muchso anos, sus mecanismos y posibles aplicaciones todavia son materia de especulacion. Entre sus caracteristicas notables se destacan la especificidad y la timodependencia. La tolerancia se manifiesta por ausencia de anticuerpos sistemicos, de hipersensibilidad de tipo retardado y de respuestas proliferativas al antigeno especifico. Los posibles mecanismos responsables de la tolerancia oral se han agrupado en tres tipos: inmunologicos, gastrointestinales e individuales. En cuanto a los inmunologicos, el mas importante podria ser la existencia de las celulas contrasupresoras, pero los mecanismos intimos de funcionaiento de estas no estan completamente elaborados. El estudio del fenomeno de la toleracia oral abre un amplio campo de invetigacion con implicaciones sobre la inmunoprofilaxis y la inmonoterapia de diferentes entidades nosologicas

The phenomenon of decreased systemic Immune response to orally administered antigens is known as oral tolerance (OT). Though It was anecdotically described many years ago, the mechanisms and potential applications of OT are still mostly speculative. Specificity and thymus-dependence are among its most remarkable features. OT is manifested by the absence of systemic antibodies, of delayed type hypersensitivity and of proliferate responses toward the specific antigen. Potential mechanisms of OT have been grouped in three types, namely: Immunologic, gastrointestinal and individual. The most Important of the immunologic mechanisms might be the existence of counter-suppressive cells but their intimate functioning has not been thoroughly elucidated. The study of OT opens a wide research field with Implications for the immunoprophylaxis and Immunotherapy of many diseases