Johnson-Hence Chelseá B, Gopalakrishna Kathyayini P, Bodkin Darren, Coffey Kara E, Burr Ansen H P, Rahman Syed, Rai Ali T, Abbott Darryl A, Sosa Yelissa A, Tometich Justin T, Das Jishnu, Hand Timothy W
R.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh PA, 15224.
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of Texas Southwestern Medical Center.
bioRxiv. 2023 Mar 20:2023.03.16.532940. doi: 10.1101/2023.03.16.532940.
Immunoglobulin A (IgA) is secreted into breast milk and is critical to both protecting against enteric pathogens and shaping the infant intestinal microbiota. The efficacy of breast milk-derived maternal IgA (BrmIgA) is dependent upon its specificity, however heterogeneity in BrmIgA binding ability to the infant microbiota is not known. Using a flow cytometric array, we analyzed the reactivity of BrmIgA against bacteria common to the infant microbiota and discovered substantial heterogeneity between all donors, independent of preterm or term delivery. We also observed intra-donor variability in the BrmIgA response to closely related bacterial isolates. Conversely, longitudinal analysis showed that the anti-bacterial BrmIgA reactivity was relatively stable through time, even between sequential infants, indicating that mammary gland IgA responses are durable. Together, our study demonstrates that the anti-bacterial BrmIgA reactivity displays inter-individual heterogeneity but intra-individual stability. These findings have important implications for how breast milk shapes the development of the infant microbiota and protects against Necrotizing Enterocolitis.
We analyze the ability of breast milk-derived Immunoglobulin A (IgA) antibodies to bind the infant intestinal microbiota. We discover that each mother secretes into their breast milk a distinct set of IgA antibodies that are stably maintained over time.
免疫球蛋白A（IgA）分泌到母乳中，对于预防肠道病原体和塑造婴儿肠道微生物群至关重要。母乳来源的母体IgA（BrmIgA）的功效取决于其特异性，然而，BrmIgA与婴儿微生物群结合能力的异质性尚不清楚。我们使用流式细胞术阵列分析了BrmIgA对婴儿微生物群常见细菌的反应性，发现所有供体之间存在显著异质性，与早产或足月分娩无关。我们还观察到供体内BrmIgA对密切相关细菌分离株的反应存在变异性。相反，纵向分析表明，抗菌BrmIgA反应性随时间相对稳定，即使在相继出生的婴儿之间也是如此，这表明乳腺IgA反应具有持久性。总之，我们的研究表明，抗菌BrmIgA反应性表现出个体间异质性但个体内稳定性。这些发现对于母乳如何塑造婴儿微生物群的发育以及预防坏死性小肠结肠炎具有重要意义。
我们分析了母乳来源的免疫球蛋白A（IgA）抗体与婴儿肠道微生物群结合的能力。我们发现，每位母亲分泌到母乳中的IgA抗体各不相同，且随时间稳定维持。
