Inborn errors of immunity and related microbiome

Abstract

Inborn errors of immunity (IEI) are characterized by diverse clinical manifestations that are dominated by atypical, recurrent, chronic, or severe infectious or non-infectious features, including autoimmunity, lymphoproliferative disease, granulomas, and/or malignancy, which contribute substantially to morbidity and mortality. Some data suggest a correlation between clinical manifestations of IEI and altered gut microbiota. Many IEI display microbial dysbiosis resulting from the proliferation of pro-inflammatory bacteria or a decrease in anti-inflammatory bacteria with variations in the composition and function of numerous microbiota. Dysbiosis is considered more established, mainly within common variable immunodeficiency, selective immunoglobulin A deficiency, severe combined immunodeficiency diseases, Wiskott–Aldrich syndrome, Hyper-IgE syndrome, autoimmune polyendocrinopathy–candidiasis–ectodermal-dystrophy (APECED), immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, IL-10 receptor deficiency, chronic granulomatous disease, and Kostmann disease. For certain IEIs, the specific predominance of gastrointestinal, respiratory, and cutaneous involvement, which is frequently associated with dysbiosis, justifies the interest for microbiome identification. With the better understanding of the relationship between gut microbiota, host immunity, and infectious diseases, the integration of microbiota modulation as a therapeutic approach or a preventive measure of infection becomes increasingly relevant. Thus, a promising strategy is to develop optimized prebiotics, probiotics, postbiotics, and fecal microbial transplantation to rebalance the intestinal microbiota and thereby attenuate the disease activity of many IEIs.

Oropharyngeal microbial ecosystem perturbations influence the risk for acute respiratory infections in common variable immunodeficiency

“…At taxonomic levels, in CVID, we observed the relative expansion of the genus Streptococcus and the decreasing abundance of the families Prevotellaceae, Fusobacteriaceae, Veillonellaceae, Campylobacteraceae , and Flavobacteriaceae , the most abundant phyla of healthy lung microbiomes ( 6 ). A similar depletion is observed in respiratory conditions such as pneumonia, COPD, and in smokers ( 32 – 37 ), together with the overgrowth of P.aeruginosa , S.pneumoniae, S.aureus, H. Influenza , and Burkholderia cepacia complex ( 11 ), leading to increased inflammation and lung injury ( 29 ). In our CVID cohort, respiratory acute infections have been positively related to the expansion of Haemophilus and Anoxybacillus , which has been previously associated with lung function worsening in Idiopathic Pulmonary Fibrosis ( 35 ) and exacerbations in asthma and COPD ( 38 , 39 ).…”

“…Secretory IgA is crucial to engendering robust host-microbial symbiosis, allowing colonization in mucosal niches through the exclusion of exogenous competitors ( 10 ). In patients with Inborn Errors of Immunity (IEI), adaptive or innate immune system defects led to gastrointestinal, respiratory, and cutaneous involvement frequently associated with dysbiosis ( 11 , 12 ). Specifically, changes in gut microbiota have been described in patients with common variable immunodeficiency (CVID) due to defects in mucosal immunity and increased microbial translocation ( 13 , 14 ), resulting in inflammation and immune dysregulation ( 13 , 15 ).…”

Microbiome and Its Dysbiosis in Inborn Errors of Immunity

“…The intestinal microbiota comprises bacteria (Lactobacillaceae, Lactococcus sp., Enterococcaceae, Bacteroidesthetaiotaomicron, Bacteroidesfragilis, and Bacteroidesovatus), viruses, protozoa, and fungi (Candida, Saccharomyces, Malassezia, and Cladosporium) [27]. Patients with inborn errors of immunity have abnormal interactions between their microbiome and immune system [28].…”

“…It was demonstrated that low microbial diversity post-HSCT leads to the emergence of Escherichia sp., Staphylococcus sp., and Enterococcus sp. [6,27,65]. Lane et al reported changes in gut microbiome composition after HSCT in cases with X-linked SCID and RAG deficiency [66,67].…”