Sara Carlotta Tagliacarne

Probiotics and Vaccination in Children

Immunisation is one of the most beneficial and cost-effective disease prevention measures. However several immunisations are associated with suboptimal seroconversion rates and so the protective effect is not optimal. In the last two decades the concept about the use of probiotic bacteria as novel mucosal adjuvants has engendered a lot of interest due to our increased immunological understanding and the availability of various techniques to enhance existing vaccine specific-immune responses. Mostly in developing countries, many people still die every year from vaccine-preventable diseases such as pneumonia and diarrhea. To date, emphasis has been placed on identifying novel vaccine antigens and adjuvants that induce stronger protective immune responses, as well as developing mucosally-administered vaccines. We would have enormous benefits in allowing safe administration of vaccines in remote areas and we may overcome the necessity for multiple doses. The precise mechanism of action of probiotics is not fully understood, but several animal and human studies have proven immunomodulatory effects involving both the humoral and cellular components of the host’s immune system. This review discusses whether dietary supplementation with oral probiotics enhances the immune response of infants after routine vaccinations and also evaluates clinical effects of probiotics in adults. Further well designed, randomized, placebo-controlled studies are needed to understand fully the immunomodulatory properties of probiotics, whether the effects exerted are strain and age-dependent, and their clinical relevance in enhancing protection following vaccination.

Gut Microbiota and Obesity.

Intestinal microbiota is composed by symbiotic innocuous bacteria and potential pathogens also called pathobionts. The human gut normally hosts roughly 1014 bacterial organisms of up to 1000 different species. The genome size of this microbial organ, collectively named microbiome, exceeds the size of the human nuclear genome by 2 orders of magnitude.

Impact of passive smoke and/or atopy on adenoid immunoglobulin production in children.

The adenoids are exposed to a wide number and variety of microbes, environmental pollutants, and food antigens. Atopy and passive smoke may significantly affect immune responses, mainly in children. The aim of the present study was to investigate whether passive exposure to tobacco smoke and/or atopy could affect immunoglobulin production by adenoidal lymphocytes in a cohort of children presenting with adenoid hypertrophy. A total of 277 children (151 males and 126 females; median age 5.5 years), with adenoidal hypertrophy requiring adenoidectomy and or adeno-tonsillectomy, were consecutively enrolled in the study. Adenoid mononuclear cells were in vitro stimulated with LPS or CpG. When considering both the presence of smoke exposure and atopy, we observed that the CpG-induced decrease in IgA and IgM production was significantly associated with this combination of risk factors. In the T-independent immunoglobulin production assay we found a positive association between the two risk factors and IgA and IgM production. In particular, the presence of both risk factors, showed a significant increase in IgA and IgM production after stimulation. In conclusion, this is the first study that investigated the in vitro adenoidal B cell response after different stimuli in children, also evaluating possible exposure to passive smoke and/or an atopic condition.

HLA-DQ genetics in children with celiac disease: A meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ β chains

BackgroundSpecific HLA-DQ genes have been recognized as necessary - but not sufficient - factors for the occurrence of Celiac Disease (CD). Through a meta-analysis, evaluating the distribution of CD-related HLA genotypes in children, we aimed at providing insights for a potential widened screening strategy.MethodsAfter a systematic search on the association between class II HLA genes and CD in children, 46 publications were obtained and assessed for eligibility. A total of 13 eligible studies were submitted to data extraction and analysis (10 case–control studies and 3 cohort studies). Case–control studies collectively enrolled 740 CD patients and 943 controls.ResultsIn the population-stratified analysis, the following alleles conferred a significantly increased risk for CD: HLA-DQB1*02 (odds ratio [OR]=10.28) and HLA-DQB1*03:02 (OR=2.24). By drafting a risk gradient to develop CD according to HLA genetic background, the highest risk is confirmed to exist for DQ2/DQ2 homozygous subjects, regardless of the ethnicities (OR=5.4). Actually, the genotype DQ2/β2 showed basically the same risk (OR=5.3). Indeed, no differences have been found in CD risk between DQ2/β2 and DQ2/DQ2, as well as between DQ8/β2 and DQ2/DQ8, and between β2/DQX and DQ2/X.ConclusionThe HLA-DQB1*02:01 allele is present in more than 90% CD children. In the perspective of a widened pediatric population screening for CD, a double-step process might be suggested: HLA-DQB1*02:01 might be investigated first and, only if this result is positive, children might be candidate for a prospective serologic screening, as a second step.

Fecal Clostridiales distribution and short-chain fatty acids reflect bowel habits in irritable bowel syndrome: Fecal microbial ecosystem of IBS subtypes

Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is classified according to bowel habits as IBS with constipation (IBS-C), with diarrhea (IBS-D), with alternating constipation and diarrhea (IBS-M), and unsubtyped (IBS-U). The mechanisms leading to the different IBS forms are mostly unknown. This study aims to evaluate whether specific fecal bacterial taxa and/or short-chain fatty acids (SCFAs) can be used to distinguish IBS subtypes and are relevant for explaining the clinical differences between IBS subcategories. We characterized five fecal samples collected at 4-weeks intervals from 40 IBS patients by 16S rRNA gene profiling and SCFA quantification. Finally, we investigated the potential correlations in IBS subtypes between the fecal microbial signatures and host physiological and clinical parameters. We found significant differences in the distribution of Clostridiales OTUs among IBS subtypes and reduced levels of SCFAs in IBS-C compared to IBS-U and IBS-D patients. Correlation analyses showed that the diverse representation of Clostridiales OTUs between IBS subtypes was associated with altered levels of SCFAs; furthermore, the same OTUs and SCFAs were associated with the fecal cytokine levels and stool consistency. Our results suggest that intestinal Clostridiales and SCFAs might serve as potential mechanistic biomarkers of IBS subtypes and represent therapeutic targets.

Detection of IL10-producing B cell (B10) in adenoids of atopic children with adenoidal hypertrophy

Introduction and background Regulatory cells are important for maintaining immunological homeostasis and tolerance to antigens, including self-antigens. Even though in the majority of autoimmune diseases and inflammatory processes, B cells generally play an important role due to their capacity to secrete antibodies, it has emerged that different B cell subsets may be able to down regulate immune responses, especially in experimental autoimmune disease models. Moreover, it has been demonstrated that B cells are able to drive T cell differentiation in favor of a regulatory phenotype (regulatory T cells, Treg) both in mice and humans [1]. In several studies the presence of Breg cells is often related to the development of chronic inflammation or autoimmune disease, but their pathogenic involvement is not completely understood. Researchers have described many B cell subsets with regulatory functions in mice, which are characterized by different surface markers, such as CD5B-1a cells, CD19CD1dCD5 B cells, or marginal zone (MZ) B cells [1]. Some studies have also suggested that human IL-10-producing B10 cells include CD24CD38 and CD24CD27 B cells, which have been identified by their capacity to produce IL10 after appropriate stimulation [2]. However, Breg cells represent an heterogeneous group of immunosuppressive cells subset with distinct phenotypic and functional properties, that could play a role also in the induction of immune tolerance to allergens. Breg-derived IL10 is involved not only in inhibition of Th1 polarization, but also in preventing Th2 responses and its expression in mucosal environment is important for the generation of immunological tolerance. Moreover, allergic disorders are characterized by an imbalance of immune response, typically defined by type 2 response and by a functional defect of Treg (3). In particular, allergic inflammation is mediated and regulated by allergen-specific Th2 cells that induce B cells to produce IgG1 and IgE by secreting IL-4. Moreover, Th2 cells also recruit eosinophils via IL-5 production and directly act on epithelial cells and smooth muscle cells through IL13 production. The development of the allergic environment, for example in asthma, could increase germinal center B cell numbers and MHC II and CD23 expression on follicular mature B cells in lung, bronchial lymph nodes (bLN) and spleen and affect the maturation of regulatory B cell subsets [3]. It is not clear if the alteration in Bregs differentiation in germinal centers is a consequence of the establishment of an allergic environment or vice versa contributes to allergic pathogenesis. Anyway, there is evidence that Breg cells are involved in allergic diseases [4]. A recent review by Palomares and colleagues highlights the importance of IL10and TFGβproducing Breg cells because of their immunosuppressive properties during allergic reaction. These cell subsets are increased both in mice and humans in response to highdose allergen exposure [4]. Bregs are able to promote * Correspondence: chiara.valsecchi@unipv.it Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia and Fondazione IRCCS Policlinico San Matteo, P.le Golgi 19, 27100 Pavia, Italy Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy Full list of author information is available at the end of the article

Low-dose multicomponent medication modulates humoral and cellular immune response in an ex-vivo study on children subjected to adenoid surgery

Respiratory infections, mainly in children, are a demanding challenge for physicians. Commonly, a relative immune-defect sustains their recurrence. At present, there is no standardized treatment for their prevention acting on the immune system. Citomix is a low-dose multicomponent medication largely used in this issue. The current study evaluated its ex vivo effect on adenoidal mononuclear cells recovered from children operated for adenoid hypertrophy. B cell phenotype, and IFN-γ, IL-6, IL-10, IgG, IgA, IgM in culture supernatants were evaluated. Citomix was able to significantly increase the expression of B memory cells, IFN-γ, IL-6, IgA and IgM, and significantly decrease IL-10 and IgG. The current outcomes could be consistent with a strategy deputed to improve the early immune response to pathogens. In conclusion, the present ex vivo study suggests that Citomix might be a promising medication in preventing and early treating respiratory infections.