{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:11:27Z","timestamp":1785413487759,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,12]]},"group-title":"Microbiology","reference-count":85,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01DK131104"],"award-info":[{"award-number":["R01DK131104"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32DK007673"],"award-info":[{"award-number":["T32DK007673"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32AI095202"],"award-info":[{"award-number":["T32AI095202"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32AI112541"],"award-info":[{"award-number":["T32AI112541"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK058404"],"award-info":[{"award-number":["DK058404"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK135073"],"award-info":[{"award-number":["DK135073"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000875","name":"Pew Charitable Trusts","doi-asserted-by":"crossref","award":["2022-A-19568"],"award-info":[{"award-number":["2022-A-19568"]}],"id":[{"id":"10.13039\/100000875","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","award":["2021\/00393-9"],"award-info":[{"award-number":["2021\/00393-9"]}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"crossref","award":["2023\/14946-5"],"award-info":[{"award-number":["2023\/14946-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,12]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Perturbation to the early-life microbiota has long-term detrimental effects on health and development, leading to increased risk for metabolic dysfunction and childhood obesity. Despite the central role of the small intestine (SI) in energy balance, the impact of SI microbiota establishment on the regulation of host metabolism and early-life adiposity remains unclear. Here, we report that disruption of a critical SI microbiota-intestinal epithelial cell circuit, specifically during a critical early-life period, drives long-lasting obesity. We demonstrate that the SI microbiota expands in abundance and diversity significantly between 2 and 3 weeks of life, and that segmented filamentous bacteria (SFB) and\n                  <jats:italic>Lactobacillus intestinalis<\/jats:italic>\n                  establish residence. Disruption of the early-life SI microbiota with antibiotics leads to enhanced lipid uptake and adiposity, driven by increased peroxisome proliferator-activated receptor alpha (PPAR\u03b1) expression and activity in SI epithelial cells (IECs). We demonstrate that SFB and\n                  <jats:italic>L. intestinalis<\/jats:italic>\n                  are key regulators of PPAR\u03b1 in SI IECs by increasing intestinal IL-22 levels specifically during weaning, which is necessary for inhibition of antibiotic-induced adiposity in a PPAR\u03b1-dependent manner. Together, this work provides mechanistic insights into beneficial microbiota-induced epithelial-immune crosstalk in the SI that is specific to early life, a critical protective mechanism against excessive adiposity in infancy, and offers insight into how antibiotics during infancy may increase the risk of childhood obesity.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>GRAPHICAL ABSTRACT<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"731695v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.11.731695","type":"posted-content","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:55:21Z","timestamp":1781326521000},"source":"Crossref","is-referenced-by-count":0,"title":["Small intestine microbiota development prevents early-life adiposity via IL-22-mediated intestinal PPAR\u03b1 suppression"],"prefix":"10.64898","author":[{"given":"Catherine D.","family":"Shelton","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Bernardo","family":"de Brito","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin\u00edcius Dias","family":"Nirello","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoinflammation, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, SP 13083-862, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Kirchoff","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute of Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Olivas","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darian T.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew W.","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merrygay N.","family":"James","sequence":"additional","affiliation":[{"name":"Vanderbilt Mouse Metabolic Phenotyping Center, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Lantier","sequence":"additional","affiliation":[{"name":"Vanderbilt Mouse Metabolic Phenotyping Center, Vanderbilt University, Nashville, TN, USA"},{"name":"Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Aur\u00e9lio","family":"Ramirez Vinolo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoinflammation, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, SP 13083-862, Brazil"},{"name":"Obesity and Comorbidities Research Center (OCRC), University of Campinas, Campinas, SP 13083-862, Brazil"},{"name":"Experimental Medicine Research Cluster, University of Campinas, Campinas, SP 13083-862, Brazil"},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia de Mucosas e Pele (INCT Mucosa e Pele), Belo Horizonte, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2122-4156","authenticated-orcid":false,"given":"Mariana 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