{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:58:10Z","timestamp":1787324290507,"version":"build-2736575974"},"posted":{"date-parts":[[2026,5,20]]},"group-title":"Microbiology","reference-count":47,"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":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01 DK070855"],"award-info":[{"award-number":["R01 DK070855"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 DK134692"],"award-info":[{"award-number":["R01 DK134692"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 DK134692"],"award-info":[{"award-number":["R01 DK134692"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R35 GM147470"],"award-info":[{"award-number":["R35 GM147470"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AI118807"],"award-info":[{"award-number":["R01 AI118807"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F31 DK126391"],"award-info":[{"award-number":["F31 DK126391"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 AI005284"],"award-info":[{"award-number":["T32 AI005284"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 DK127984"],"award-info":[{"award-number":["P30 DK127984"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P01 HL160487"],"award-info":[{"award-number":["P01 HL160487"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"crossref","award":["I-1874"],"award-info":[{"award-number":["I-1874"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"crossref","award":["PATH Award #1017880"],"award-info":[{"award-number":["PATH Award #1017880"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011684","name":"Crohn's and Colitis Foundation","doi-asserted-by":"crossref","award":["#1440322"],"award-info":[{"award-number":["#1440322"]}],"id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"crossref","award":["Investigator Support for Lora V. Hooper"],"award-info":[{"award-number":["Investigator Support for Lora V. Hooper"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Enteric bacterial pathogens profoundly alter intestinal physiology during infection, yet their effects on host lipid metabolism remain poorly understood. Using mass spectrometry lipidomics, we found that infection of the mouse intestine with the bacterial pathogen\n                  <jats:italic>Salmonella enterica<\/jats:italic>\n                  serovar Typhimurium (\n                  <jats:italic>S<\/jats:italic>\n                  . Typhimurium) stimulates uptake of long-chain fatty acids by small intestinal epithelial cells. This response coincided with increased expression of epithelial genes involved in lipid uptake and transport and required the long-chain fatty acid transporter CD36. Fatty acid uptake was triggered by\n                  <jats:italic>S<\/jats:italic>\n                  . Typhimurium lipopolysaccharide (LPS) and was impaired by bacterial mutations that alter LPS acyl chains. Mechanistically,\n                  <jats:italic>S<\/jats:italic>\n                  . Typhimurium induced lipid absorption through myeloid cell Toll-like receptor 4, a receptor for LPS.\n                  <jats:italic>Escherichia coli<\/jats:italic>\n                  , a related commensal bacterium, also induced intestinal lipid absorption through LPS, although to a lesser extent than\n                  <jats:italic>S<\/jats:italic>\n                  . Typhimurium. Finally, disruption of long-chain fatty acid absorption impaired host defense during bacterial stimulation, suggesting that bacteria-induced lipid uptake contributes to protection against enteric infection. Together, these findings identify LPS from Gram-negative intestinal bacteria as a key regulator of dietary lipid uptake by the intestinal epithelium.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>\n                    The intestinal lining absorbs nutrients while also detecting bacteria that enter with food, but how these two functions intersect during infection is poorly understood.\n                    <jats:italic>Salmonella<\/jats:italic>\n                    is a food-borne bacterial pathogen that infects humans. By studying mice, we found that\n                    <jats:italic>Salmonella<\/jats:italic>\n                    infection rapidly enhances absorption of dietary lipids by intestinal epithelial cells. This response was triggered when immune cells beneath the gut lining detected lipopolysaccharide, a molecule in the outer coat of many Gram-negative bacteria. In mice with defective lipid absorption, more\n                    <jats:italic>Salmonella<\/jats:italic>\n                    spread beyond the intestine, suggesting that lipid uptake contributes to host defense. These findings reveal a previously unappreciated link between microbial sensing, nutrient absorption, and defense against intestinal infection.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.19.726283","type":"posted-content","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:55:25Z","timestamp":1779339325000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Salmonella<\/i>\n                  lipopolysaccharide stimulates uptake of long-chain fatty acids in the small intestine"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6190-7242","authenticated-orcid":false,"given":"Eugene","family":"Koo","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1574-8778","authenticated-orcid":false,"given":"Gabriella","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassie L.","family":"Behrendt","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Hassell","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-5360","authenticated-orcid":false,"given":"Katie N.","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Ruhn","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gon\u00e7alo","family":"Vale","sequence":"additional","affiliation":[{"name":"Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390"},{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey G.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390"},{"name":"Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3771-0842","authenticated-orcid":false,"given":"Wenhan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1532-9178","authenticated-orcid":false,"given":"Sebastian E.","family":"Winter","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, UC Davis School of Medicine, Davis, CA 95616"},{"name":"Department of Medical Microbiology and Immunology, UC Davis School of Medicine, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2759-4641","authenticated-orcid":false,"given":"Lora V.","family":"Hooper","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390"},{"name":"The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026082107100602000_2026.05.19.726283v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11552"},{"key":"2026082107100602000_2026.05.19.726283v2.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407076101"},{"key":"2026082107100602000_2026.05.19.726283v2.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605374104"},{"key":"2026082107100602000_2026.05.19.726283v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.03.011"},{"key":"2026082107100602000_2026.05.19.726283v2.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan0677"},{"key":"2026082107100602000_2026.05.19.726283v2.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade0522"},{"key":"2026082107100602000_2026.05.19.726283v2.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw3134"},{"key":"2026082107100602000_2026.05.19.726283v2.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050244"},{"key":"2026082107100602000_2026.05.19.726283v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/nature12503"},{"key":"2026082107100602000_2026.05.19.726283v2.10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10501"},{"key":"2026082107100602000_2026.05.19.726283v2.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.1179721"},{"key":"2026082107100602000_2026.05.19.726283v2.12","doi-asserted-by":"publisher","DOI":"10.1038\/nature24489"},{"key":"2026082107100602000_2026.05.19.726283v2.13","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00933-08"},{"key":"2026082107100602000_2026.05.19.726283v2.14","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071812-161220"},{"key":"2026082107100602000_2026.05.19.726283v2.15","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.27.061406.093710"},{"key":"2026082107100602000_2026.05.19.726283v2.16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00098.2014"},{"key":"2026082107100602000_2026.05.19.726283v2.17","doi-asserted-by":"publisher","DOI":"10.1021\/bi00437a001"},{"key":"2026082107100602000_2026.05.19.726283v2.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.10.014"},{"key":"2026082107100602000_2026.05.19.726283v2.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2006.01.004"},{"key":"2026082107100602000_2026.05.19.726283v2.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0250-7"},{"key":"2026082107100602000_2026.05.19.726283v2.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00561-4"},{"key":"2026082107100602000_2026.05.19.726283v2.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.07.018"},{"key":"2026082107100602000_2026.05.19.726283v2.23","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.010307.145803"},{"key":"2026082107100602000_2026.05.19.726283v2.24","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00952.x"},{"key":"2026082107100602000_2026.05.19.726283v2.25","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01204.x"},{"key":"2026082107100602000_2026.05.19.726283v2.26","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5396.2085"},{"key":"2026082107100602000_2026.05.19.726283v2.27","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80086-2"},{"key":"2026082107100602000_2026.05.19.726283v2.28","doi-asserted-by":"publisher","DOI":"10.1038\/nature10558"},{"key":"2026082107100602000_2026.05.19.726283v2.29","doi-asserted-by":"publisher","DOI":"10.1126\/science.1240248"},{"key":"2026082107100602000_2026.05.19.726283v2.30","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.16.5432-5441.2004"},{"key":"2026082107100602000_2026.05.19.726283v2.31","doi-asserted-by":"publisher","DOI":"10.1159\/000071854"},{"key":"2026082107100602000_2026.05.19.726283v2.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.007"},{"key":"2026082107100602000_2026.05.19.726283v2.33","doi-asserted-by":"crossref","unstructured":"E. d\u2019Hennezel , S. Abubucker , L. O. Murphy , T. W. Cullen , Total lipopolysaccharide from the human gut microbiome silences Toll-like receptor signaling. mSystems 2 (2017).","DOI":"10.1128\/mSystems.00046-17"},{"key":"2026082107100602000_2026.05.19.726283v2.34","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.138"},{"key":"2026082107100602000_2026.05.19.726283v2.35","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.107"},{"key":"2026082107100602000_2026.05.19.726283v2.36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2316579120"},{"key":"2026082107100602000_2026.05.19.726283v2.37","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1491"},{"key":"2026082107100602000_2026.05.19.726283v2.38","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1403"},{"key":"2026082107100602000_2026.05.19.726283v2.39","doi-asserted-by":"publisher","DOI":"10.1038\/nature14232"},{"key":"2026082107100602000_2026.05.19.726283v2.40","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.117"},{"key":"2026082107100602000_2026.05.19.726283v2.41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605200103"},{"key":"2026082107100602000_2026.05.19.726283v2.42","doi-asserted-by":"publisher","DOI":"10.1172\/jci99315"},{"key":"2026082107100602000_2026.05.19.726283v2.43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204935200"},{"key":"2026082107100602000_2026.05.19.726283v2.44","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008942828960"},{"key":"2026082107100602000_2026.05.19.726283v2.45","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062648"},{"key":"2026082107100602000_2026.05.19.726283v2.46","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.5.1357-1366.1995"},{"key":"2026082107100602000_2026.05.19.726283v2.47","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.6.3367-3374.2005"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.19.726283","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:21:32Z","timestamp":1787322092000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.19.726283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":47,"URL":"https:\/\/doi.org\/10.64898\/2026.05.19.726283","relation":{},"subject":[],"published":{"date-parts":[[2026,5,20]]},"subtype":"preprint"}}