PhIP-Seq characterization of serum antibodies using oligonucleotide-encoded peptidomes. Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Analysis of bacterial-surface-specific antibodies in body fluids using bacterial flow cytometry. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomes spanning age, geography and lifestyle. An atlas of B-cell clonal distribution in the human body. ![]() Analysis of the B cell receptor repertoire in six immune-mediated diseases. Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota. Commonality despite exceptional diversity in the baseline human antibody repertoire. High frequency of shared clonotypes in human B cell receptor repertoires. The antibody/microbiota interface in health and disease. Mucosal or systemic microbiota exposures shape the B cell repertoire. Synergistic convergence of microbiota-specific systemic IgG and secretory IgA. Commensal microbes induce serum IgA responses that protect against polymicrobial sepsis. Gut microbiota-induced immunoglobulin G controls systemic infection by symbiotic bacteria and pathogens. The maternal microbiota drives early postnatal innate immune development. Maternal IgG and IgA antibodies dampen mucosal T helper cell responses in early life. Current understanding of the human microbiome. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Antigens included in the PhIP-Seq library were obtained from the immune epitope database (IEDB, ) and virulence factor database (VFDB, ), as well as other sources outlined in the Methods. Raw data for the PhIP-Seq experiments are deposited in the Harvard Dataverse public repository at. 4a,c have associated raw data provided, respectively, in Supplementary Table 2, Supplementary Table 3, Supplementary Table 4, Supplementary Table 5 and Supplementary Table 6. Patient-related data not included in the paper may be subject to patient confidentiality. Detailed information on the cohort, library content and PhIP-Seq data are available in the Supplementary Data files (files: cohort_info.csv, MB_composition.csv, library_content_info.csv and PhIP-Seq_data.zip). The data generated or analyzed during this study are included within the paper, its Supplementary Information files and public repositories. Overall, our results suggest that systemic antibody responses provide a non-redundant layer of information about microbiota beyond gut microbial species composition. Serum samples of more than 200 individuals collected five years apart could be accurately matched and could serve as an immunologic fingerprint. We also demonstrate that these antibody epitope repertoires are more longitudinally stable than gut microbiome species abundances. Leveraging phage immunoprecipitation sequencing (PhIP-Seq) based on phage-displayed synthetic oligo libraries, we detect a wide breadth of individual-specific as well as shared antibody responses against microbiota that associate with age and gender. ![]() Here we have profiled the serum antibody responses of 997 healthy individuals against 244,000 rationally selected peptide antigens derived from gut microbiota and pathogenic and probiotic bacteria. However, our current understanding of antibody repertoires is largely based on DNA sequencing of the corresponding B-cell receptor genes, and actual bacterial antigen targets remain incompletely characterized. Serum antibodies can recognize both pathogens and commensal gut microbiota.
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