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Metagenomic Immunoglobulin Sequencing (MIG-Seq) Exposes Patterns of IgA Antibody Binding in the Healthy Human Gut Microbiome

2023/11/21 by Matthew R. Olm, Sean P. Spencer, Evelyn Lemus Silva +1 · 1 voice · 2 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Antibody #Biology #Computational biology #Gene #Genetics #Gut microbiota and health #Human microbiome #Immune Cell Function and Interaction #Immune system #Immunodeficiency and Autoimmune Disorders #Immunoglobulin A #Immunoglobulin G #Immunology #Metagenomics #Microbiology #Microbiome #Mucus #Secretory IgA

paper · pdf · doi:10.1101/2023.11.21.568153

published in bioRxiv (Cold Spring Harbor Laboratory) (Cold Spring Harbor Laboratory)

openalex publication_date 2023/11/21 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06

Abstract

IgA, the most highly produced human antibody, is continually secreted into the gut to shape the intestinal microbiota. Methodological limitations have critically hindered defining which microbial strains are targeted by IgA and why. Here, we develop a new technique, Metagenomic Immunoglobulin Sequencing (MIG-Seq), and use it to determine IgA coating levels for thousands of gut microbiome strains in healthy humans. We find that microbes associated with both health and disease have higher levels of coating, and that microbial genes are highly predictive of IgA binding levels, with mucus degradation genes especially correlated with high binding. We find a significant reduction in replication rates among microbes bound by IgA, and demonstrate that IgA binding is more correlated with host immune status than traditional microbial abundance measures. This study introduces a powerful technique for assessing strain-level IgA binding in human stool, paving the way for deeper understanding of IgA-based host microbe interactions.

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