Immunomodulation of B Lymphocytes by Prebiotics, Probiotics and Synbiotics: Application in Pathologies.

INTRODUCTION: Prebiotics, probiotics and synbiotics are known to have major beneficial effects on human health due to their ability to modify the composition and the function of the gut mucosa, the gut microbiota and the immune system. These components largely function in a healthy population throughout different periods of life to confer homeostasis. Indeed, they can modulate the composition of the gut microbiota by increasing bacteria strands that are beneficial for health, such as Firmicute and Bifidobacteria, and decreasing harmful bacteria, such as Enteroccocus. Their immunomodulation properties have been extensively studied in different innate cells (dendritic cells, macrophages, monocytes) and adaptive cells (Th, Treg, B cells). They can confer a protolerogenic environment but also modulate pro-inflammatory responses. Due to all these beneficial effects, these compounds have been investigated to prevent or to treat different diseases, such as cancer, diabetes, allergies, autoimmune diseases, etc. Regarding the literature, the effects of these components on dendritic cells, monocytes and T cells have been studied and presented in a number of reviews, but their impact on B-cell response has been less widely discussed. CONCLUSIONS: For the first time, we propose here a review of the literature on the immunomodulation of B-lymphocytes response by prebiotics, probiotics and synbiotics, both in healthy conditions and in pathologies. DISCUSSION: Promising studies have been performed in animal models, highlighting the potential of prebiotics, probiotics and synbiotics intake to treat or to prevent diseases associated with B-cell immunomodulation, but this needs to be validated in humans with a full characterization of B-cell subsets and not only the humoral response.

Human Milk Oligosaccharides: Their Effects on the Host and Their Potential as Therapeutic Agents.

Breastmilk is known to be very important for infants because it provides nutrients and immunological compounds. Among these compounds, human milk oligosaccharides (HMOs) represent the third most important component of breastmilk after lipids and lactose. Several experiments demonstrated the beneficial effects of these components on the microbiota, the immune system and epithelial barriers, which are three major biological systems. Indeed, HMOs induce bacterial colonization in the intestinal tract, which is beneficial for health. The gut bacteria can act directly and indirectly on the immune system by stimulating innate immunity and controlling inflammatory reactions and by inducing an adaptive immune response and a tolerogenic environment. In parallel, HMOs directly strengthen the intestinal epithelial barrier, protecting the host against pathogens. Here, we review the molecular mechanisms of HMOs in these different compartments and highlight their potential use as new therapeutic agents, especially in allergy prevention.

Prebiotic Supplementation During Gestation Induces a Tolerogenic Environment and a Protective Microbiota in Offspring Mitigating Food Allergy.

Food allergy is associated with alterations in the gut microbiota, epithelial barrier, and immune tolerance. These dysfunctions are observed within the first months of life, indicating that early intervention is crucial for disease prevention. Preventive nutritional strategies with prebiotics are an attractive option, as prebiotics such as galacto-oligosaccharides and inulin can promote tolerance, epithelial barrier reinforcement, and gut microbiota modulation. Nonetheless, the ideal period for intervention remains unknown. Here, we investigated whether galacto-oligosaccharide/inulin supplementation during gestation could protect offspring from wheat allergy development in BALB/cJRj mice. We demonstrated that gestational prebiotic supplementation promoted the presence of beneficial strains in the fecal microbiota of dams during gestation and partially during mid-lactation. This specific microbiota was transferred to their offspring and maintained to adulthood. The presence of B and T regulatory immune cell subsets was also increased in the lymph nodes of offspring born from supplemented mothers, suggestive of a more tolerogenic immune environment. Indeed, antenatal prebiotic supplementation reduced the development of wheat allergy symptoms in offspring. Our study thus demonstrates that prebiotic supplementation during pregnancy induces, in the offspring, a tolerogenic environment and a microbial imprint that mitigates food allergy development.

Epidermal micro-perforation potentiates the efficacy of epicutaneous vaccination.

The skin is an immune organ comprised of a large network of antigen-presenting cells such as dendritic cells, making it an attractive target for the development of new vaccines and immunotherapies. Recently, we developed a new innovative and non-invasive vaccination method without adjuvant based on epicutaneous vaccine patches on which antigen forms a dry deposit. Here we describe in mice a method for potentiating the efficacy of our epicutaneous vaccination approach using a minimally invasive and epidermis-limited skin preparation based on laser-induced micro-perforation. Our results showed that epidermal micro-perforation increased trans-epidermal water loss, resulting in an enhancement of antigen solubilization from the surface of the patch, and increased the quantity of antigen delivered to the epidermis. Importantly, this was not associated with an increase in systemic passage of the antigen. Skin micro-perforation slightly activated keratinocytes without inducing an excessive level of local inflammation. Moreover, epidermal micro-perforation improved antigen capture by epidermal dendritic cells and specifically increased the level of Langerhans cells activation. Finally, we observed that epidermal micro-perforation significantly increased the level of the specific antibody response induced by our epicutaneous Pertussis vaccine candidate containing non-adsorbed recombinant Pertussis Toxin and reduced the amount of antigen dose required. Overall, these data confirm the benefit of a minimal and controlled epidermal preparation for improving the effectiveness of an epicutaneous patch-based vaccine, without adversely affecting the safety of the method.