{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T10:02:44Z","timestamp":1779703364451,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,20]]},"group-title":"Microbiology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"Colorado Nutrition Obesity Research Center (NORC) Pilot & Feasibility Program Award","award":["P30DK048250"],"award-info":[{"award-number":["P30DK048250"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK126710"],"award-info":[{"award-number":["R01DK126710"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>IgA is the dominant antibody in the human gut and a key regulator of host-microbe interactions. Infants begin to produce IgA at around 6 months old and receive large quantities of IgA via human milk, but technical limitations have prevented species-level characterization of IgA binding in early life. This has left basic knowledge gaps about which species are targeted by IgA in infancy, and how modifiable lifestyle factors like breastfeeding and complementary feeding impact IgA targeting.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Here we adapt Metagenomic Immunoglobulin Sequencing (MIg-Seq) for low-biomass infant fecal samples and apply this optimized protocol to 32 longitudinal samples from 16 infants enrolled in the MINT trial, a four-arm randomized controlled trial comparing meat-based, dairy-based, plant-based, and reference complementary feeding patterns, with fecal sampling at 6 and 12 months (pre and post intervention). Infant IgA targeting mirrors adults at the phylum level, with both age groups showing significantly higher IgA targeting of Pseudomonadota and lower targeting of Bacteroidota relative to other phyla. During the substantial microbiome compositional shifts noted between 6 and 12 months, IgA targeting is significantly more stable than the microbiome itself. Among persistent colonizers, IgA targeting strengthens significantly from 6 to 12 months, with the most pronounced effect observed for\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    , a finding robust across all dietary arms and feeding modes. The feeding arm to which infants were enrolled was not significantly associated with IgA binding, but several nutrient-specific associations were discovered. Animal-derived nutrients, particularly cholesterol, are strongly positively correlated with IgA targeting of\n                    <jats:italic>Bifidobacterium longum<\/jats:italic>\n                    , while plant-derived carotenoids are positively associated with IgA targeting of\n                    <jats:italic>Flavonifractor plautii<\/jats:italic>\n                    and\n                    <jats:italic>Ruminococcus gnavus<\/jats:italic>\n                    .\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    This study introduces an experimental and computational framework for species-level IgA profiling in the infant gut. The progressive strengthening of IgA targeting of\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    and other beneficial persistent colonizers suggests a role for IgA in reinforcing beneficial microbes during infancy. The nutrient-specific dietary effects on IgA targeting reveal the immunological consequences of the complementary feeding period, and highlight a contrast between animal-versus plant-based diets. Together, these findings point to early nutritional interventions and IgA-based therapeutics as promising tools for promoting healthy immune-microbiome development.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.19.726352","type":"posted-content","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:20:11Z","timestamp":1779340811000},"source":"Crossref","is-referenced-by-count":0,"title":["IgA Targeting in the Infant Gut Is Modulated by Diet and Increasingly Directed Towards Persistent Species"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-8688","authenticated-orcid":false,"given":"Jing","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4112-2105","authenticated-orcid":false,"given":"Parsa","family":"Ghadermazi","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0723-8036","authenticated-orcid":false,"given":"Soren","family":"Maret","sequence":"additional","affiliation":[{"name":"Molecular, Cellular, and Developmental Biology Department, University of Colorado Boulder, Boulder, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6495-9104","authenticated-orcid":false,"given":"Jennifer F.","family":"Kemp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Nutrition, University of Colorado School of Medicine, Aurora, CO, USA"},{"name":"Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Medicine-Infectious Disease, University of Colorado School of Medicine, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward L.","family":"Melanson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey E.","family":"Hendricks","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Krebs","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Nutrition, University of Colorado School of Medicine, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghua","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5540-350X","authenticated-orcid":false,"given":"Matthew R.","family":"Olm","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052502050854000_2026.05.19.726352v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4142"},{"key":"2026052502050854000_2026.05.19.726352v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-019-0191-8"},{"key":"2026052502050854000_2026.05.19.726352v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.77"},{"key":"2026052502050854000_2026.05.19.726352v1.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaq0926"},{"key":"2026052502050854000_2026.05.19.726352v1.5","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41385-019-0227-4","article-title":"IgA and the intestinal microbiota: the importance of being specific","volume":"13","year":"2020","journal-title":"Mucosal Immunology"},{"key":"2026052502050854000_2026.05.19.726352v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nature22058"},{"key":"2026052502050854000_2026.05.19.726352v1.7","doi-asserted-by":"crossref","unstructured":"Rio-Aige, K. et al. 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Next-generation IgA-SEQ allows for high-throughput, anaerobic, and metagenomic assessment of IgA-coated bacteria. Microbiome 12, 211 (2024).","DOI":"10.1186\/s40168-024-01923-9"},{"key":"2026052502050854000_2026.05.19.726352v1.17","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41564-024-01887-4","article-title":"Metagenomic immunoglobulin sequencing reveals IgA coating of microbial strains in the healthy human gut","volume":"10","year":"2025","journal-title":"Nat Microbiol"},{"key":"2026052502050854000_2026.05.19.726352v1.18","unstructured":"Viladomiu, M. et al. IgA-coated enriched in Crohn\u2019s disease spondyloarthritis promote T17-dependent inflammation. Sci Transl Med 9, (2017)."},{"key":"2026052502050854000_2026.05.19.726352v1.19","doi-asserted-by":"crossref","unstructured":"Tang, M. et al. Effects of Complementary Feeding With Different Protein-Rich Foods on Infant Growth and Gut Health: Study Protocol. 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