Expanded microbiome niches of RAG-deficient patients

The complex interplay between microbiota and immunity is important to human health. To explore how altered adaptive immunity influences the microbiome, we characterize skin, nares, and gut microbiota of patients with recombination-activating gene (RAG) deficiency—a rare genetically defined inborn error of immunity (IEI) that results in a broad spectrum of clinical phenotypes. Integrating de novo assembly of metagenomes from RAG-deficient patients with reference genome catalogs provides an expansive multi-kingdom view of microbial diversity. RAG-deficient patient microbiomes exhibit inter-individual variation, including expansion of opportunistic pathogens (e.g., Corynebacterium bovis, Haemophilus influenzae), and a relative loss of body site specificity. We identify 35 and 27 bacterial species derived from skin/nares and gut microbiomes, respectively, which are distinct to RAG-deficient patients compared to healthy individuals. Underscoring IEI patients as potential reservoirs for viral persistence and evolution, we further characterize the colonization of eukaryotic RNA viruses (e.g., Coronavirus 229E, Norovirus GII) in this patient population. [Display omitted] •Patients with RAG deficiency harbor distinct skin, nasal, and gut microbiomes•Metagenome-assembled genomes colonizing RAG-deficient patients expand microbial diversity•Enriched antimicrobial resistance gene content among microbiota of RAG-deficient patients Blaustein et al. explore microbiome diversity associated with recombination-activating gene (RAG) deficiency. Patients harbor highly individual microbial communities with expanded diversity and a relative loss in body site specificity. Increased bacterial and viral diversity, including potential pathogens, are observed in this immunodeficient population.