Increasing evidence indicates that gut microorganisms impact multiple aspects of the innate and adaptive mucosal immune system. Current research focuses on the potential of prebiotics (non-digestible fibres that nourish beneficial bacteria) and probiotics (beneficial live bacteria) to promote health, prevent disease, and for use as a treatment strategy for a variety of immune-mediated conditions. The immune modulatory effects of probiotics and prebiotics are strain- or structure-specific and vary with disease state, age, and sex. Prebiotics and live beneficial bacteria, including their metabolic products or soluble mediators, have the ability to affect the composition of the intestinal microbiota. As well, they influence the integrity and functions of intestinal epithelial cells and antigen presenting cells, including dendritic cells and macrophages, by both direct and indirect mechanisms of action.Statement of novelty: This review serves to highlight select advances related to the impact of prebiotics, probiotics, and gut microbe-derived metabolites on host immune function.

Background: Interleukin-12 Receptor β1 (IL-12Rβ1) deficiency causes susceptibility to weakly virulent atypical mycobacteria and Salmonella. Genotype–phenotype correlations are weak and penetrance is not complete. Most of the culture-recovered Salmonella are with the non typhi types.Case report: We describe an 11 year old male patient with IL-12Rβ1 deficiency. He had an erythematous rash resembling Henoch Schonlein Purpura, and initially presented with slightly elevated CRP. Skin biopsy revealed leukocytoclastic vasculitis. Due to lack of evidence of an active infection, positive ANA, and positive direct Coombs test, an autoimmune lupus-like disease was suspected. In conjunction with rash flares, he showed progressively elevated inflammatory markers, chronic anemia, and hypoalbuminemia. Extensive investigations for an infectious etiology were negative, and without isolation of any pathogens. However, the last of a series of abdominal ultrasound examinations revealed enlarged peritoneal and retroperitoneal lymph-nodes, and biopsy yielded slow-growing bacteria, identified as Salmonella typhi. Prolonged treatment with 2 antimicrobial agents resulted in resolution of skin rash and normalization of laboratory results.Conclusions: We describe an IL-12Rβ1 deficient patient with a progressive inflammatory process with a unique immune dermatological manifestation which was probably triggered by an unexpected pathogen, Salmonella typhi. This patient’s case demonstrates the need for invasive procedures to identify an infectious etiology when routine cultures and serology tests are negative.Statement of novelty: In this case report, we describe a unique presentation of infection with Salmonella typhi in a patient with IL-12Rβ1 deficiency, manifesting with bouts of leucocytoclastic vasculitis. We also report in the same patient, recurrent infection with an unusual pathogen, Kocuria kristinae. Both phenomena have not been reported in such constellation, and we believe this to be a useful and important description that could alert physicians, immunologists, and pediatricians alike to such manifestations. Further, it may help in a rapid and successful diagnosis, therefore benefiting such patients.

Background: DNA ligase IV deficiency is a rare autosomal recessive condition resulting from mutations in LIG4, an essential component of the non-homologous end-joining pathway that prevents mutagenesis and apoptosis. Patients with LIG4 deficiency present with varying degrees of combined immunodeficiency, or less commonly, severe combined immunodeficiency (SCID). Assessment of thymus pathology has been instrumental in defining a growing number of T cell deficiencies. In this case report, we present thymic histopathology of a LIG4 deficient patient who presented with SCID.Methods: Whole exome sequencing and Sanger confirmation were used to identify a novel mutation in LIG4. Standard immune work up and histopathology were completed to characterize deficits in immune function and dysplastic thymic architecture in our patient.Results: Next generation sequencing techniques identified a homozygous c.1102G>T, resulting in amino acid change D368Y in the adenylation domain of LIG4. Histopathology revealed a distinct absence of Hassall’s corpuscles, lack of cortico-medullary demarcation, as well as lack of T cells and Langerhans histiocytes in the thymic medulla.Conclusion: We have identified a novel mutation in LIG4 resulting in a SCID phenotype. Underdevelopment of the thymus, characterized by a lack of Hassall’s corpuscles and competent thymocytes, likely contributes to the immune defects observed in patients with mutations in LIG4.Statement of novelty: We report here a novel mutation in LIG4 as well as the first description of detailed thymus pathology in this condition.