{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:59:53Z","timestamp":1791485993927,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pbio.3004026","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM0709077"],"award-info":[{"award-number":["GM0709077"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI117911"],"award-info":[{"award-number":["AI117911"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    Animals must allocate limited energetic resources across competing defense programs in response to infection. Here, we show that the conserved nuclear hormone receptor NHR-68 integrates fatty acid metabolism with the neural control of molecular and behavioral immunity in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    . Acting in parallel with NHR-10, NHR-68 controls genes involved in polyunsaturated fatty acid (PUFA) metabolism. Loss of NHR-68 disrupts linoleic acid (LA) homeostasis, impairing pathogen avoidance behavior. Supplementation with LA restores avoidance, and\n                    <jats:italic>fat-3<\/jats:italic>\n                    inhibition, which elevates LA, enhances pathogen avoidance, whereas loss of LA synthesis by\n                    <jats:italic>fat-2<\/jats:italic>\n                    inhibition diminishes this behavior, indicating that LA promotes behavioral immunity. We further show that NHR-68 acts in the intestine to regulate linoleic acid homeostasis, and that changes in intestinal lipid metabolism influence an AWC-dependent pathogen-avoidance circuit through intestine-to-neuron communication. NHR-68 suppresses activation of the PMK-1\/p38 MAPK and DAF-16\/FOXO pathways, which mediate molecular immune responses. These findings identify a gut-brain transcriptional circuit that connects intestinal lipid metabolism to neural and immune outputs, revealing a mechanism by which the metabolic state coordinates behavioral and molecular defenses to optimize host protection.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3004026","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:31:07Z","timestamp":1790703067000},"page":"e3004026","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intestinal lipid metabolism controls molecular and behavioral immunity through NHR-68 and gut\u2013brain signaling in Caenorhabditis elegans"],"prefix":"10.1371","volume":"24","author":[{"given":"Jie","family":"Ren","sequence":"first","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center","place":["Houston, Texas, United States of America"],"department":["Department of Genetics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2981-1582","authenticated-orcid":true,"given":"Yu","family":"Sang","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center","place":["Houston, Texas, United States of America"],"department":["Department of Genetics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8972-7593","authenticated-orcid":true,"given":"Young-Mo","family":"Kim","sequence":"additional","affiliation":[{"name":"Pacific Northwest National Laboratory","place":["Richland, Washington, United States of America"],"department":["Biological Sciences Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto S.","family":"Nakayasu","sequence":"additional","affiliation":[{"name":"Pacific Northwest National Laboratory","place":["Richland, Washington, United States of America"],"department":["Biological Sciences Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5975-3352","authenticated-orcid":true,"given":"Alejandro","family":"Aballay","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center","place":["Houston, Texas, United States of America"],"department":["Department of Genetics"]},{"name":"McGovern Medical School at UTHealth","place":["Houston, Texas, United States of America"],"department":["Department of Microbiology and Molecular Genetics"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"issue":"6","key":"pbio.3004026.ref001","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/0092-8674(95)90199-X","article-title":"The nuclear receptor superfamily: the second decade","volume":"83","author":"DJ Mangelsdorf","year":"1995","journal-title":"Cell"},{"issue":"7","key":"pbio.3004026.ref002","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41574-020-0349-5","article-title":"Nuclear receptor crosstalk - defining the mechanisms for therapeutic innovation","volume":"16","author":"K De Bosscher","year":"2020","journal-title":"Nat Rev Endocrinol"},{"issue":"1","key":"pbio.3004026.ref003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3003627","article-title":"A gut-activated NHR-86-CYP pathway mediates the neuroprotective effects of Enterococcus faecium probiotics in a nematode model of amyotrophic lateral sclerosis","volume":"24","author":"Y Sang","year":"2026","journal-title":"PLoS Biol"},{"issue":"3","key":"pbio.3004026.ref004","article-title":"NHR-49\/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting","volume":"17","author":"GYS Goh","year":"2018","journal-title":"Aging Cell"},{"issue":"4","key":"pbio.3004026.ref005","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/acel.12218","article-title":"A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans","volume":"13","author":"M Chamoli","year":"2014","journal-title":"Aging Cell"},{"key":"pbio.3004026.ref006","article-title":"Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans","volume":"11","author":"KRS Doering","year":"2022","journal-title":"Elife"},{"key":"pbio.3004026.ref007","article-title":"NHR-49\/PPAR-\u03b1 and HLH-30\/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase","volume":"10","author":"KA Wani","year":"2021","journal-title":"Elife"},{"issue":"7","key":"pbio.3004026.ref008","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13413","article-title":"Cell nonautonomous roles of NHR-49 in promoting longevity and innate immunity","volume":"20","author":"N Naim","year":"2021","journal-title":"Aging Cell"},{"issue":"8","key":"pbio.3004026.ref009","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00130-20","article-title":"NHR-49 Transcription factor regulates immunometabolic response and survival of Caenorhabditis elegans during Enterococcus faecalis infection","volume":"88","author":"M Dasgupta","year":"2020","journal-title":"Infect Immun"},{"issue":"1","key":"pbio.3004026.ref010","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007935","article-title":"The nuclear hormone receptor NHR-86 controls anti-pathogen responses in C. elegans","volume":"15","author":"ND Peterson","year":"2019","journal-title":"PLoS Genet"},{"issue":"10","key":"pbio.3004026.ref011","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1011730","article-title":"Transcriptional suppression of sphingolipid catabolism controls pathogen resistance in C. elegans","volume":"19","author":"MA Nasrallah","year":"2023","journal-title":"PLoS Pathog"},{"issue":"4","key":"pbio.3004026.ref012","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.immuni.2023.01.027","article-title":"Non-canonical pattern recognition of a pathogen-derived metabolite by a nuclear hormone receptor identifies virulent bacteria in C. elegans","volume":"56","author":"ND Peterson","year":"2023","journal-title":"Immunity"},{"issue":"8","key":"pbio.3004026.ref013","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2001-2-8-research0029","article-title":"Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drosophila genomes","volume":"2","author":"JM Maglich","year":"2001","journal-title":"Genome Biol"},{"key":"pbio.3004026.ref014","article-title":"RiboTRAP-seq identifies spatially distinct functions for the anterior and posterior intestine in immune and metabolic regulation in C. elegans","author":"CC Liu","year":"2025","journal-title":"bioRxiv"},{"issue":"1","key":"pbio.3004026.ref015","doi-asserted-by":"crossref","first-page":"6869","DOI":"10.1038\/s41467-024-51077-3","article-title":"A homeostatic gut-to-brain insulin antagonist restrains neuronally stimulated fat loss","volume":"15","author":"C-C Liu","year":"2024","journal-title":"Nat Commun"},{"issue":"7816","key":"pbio.3004026.ref016","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41586-020-2395-5","article-title":"A neurotransmitter produced by gut bacteria modulates host sensory behaviour","volume":"583","author":"MP O\u2019Donnell","year":"2020","journal-title":"Nature"},{"issue":"10","key":"pbio.3004026.ref017","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1016\/j.celrep.2020.02.050","article-title":"Intestine-to-germline transmission of epigenetic information intergenerationally ensures systemic stress resistance in C. elegans","volume":"30","author":"M Nono","year":"2020","journal-title":"Cell Rep"},{"issue":"7065","key":"pbio.3004026.ref018","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature04216","article-title":"Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans","volume":"438","author":"Y Zhang","year":"2005","journal-title":"Nature"},{"key":"pbio.3004026.ref019","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.50033","article-title":"Intestinal infection regulates behavior and learning via neuroendocrine signaling","volume":"8","author":"J Singh","year":"2019","journal-title":"Elife"},{"key":"pbio.3004026.ref020","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.65935","article-title":"TRPM channels mediate learned pathogen avoidance following intestinal distention","volume":"10","author":"A Filipowicz","year":"2021","journal-title":"Elife"},{"issue":"2","key":"pbio.3004026.ref021","article-title":"Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans","volume":"3","author":"MR Van Gilst","year":"2005","journal-title":"PLoS Biol"},{"issue":"4","key":"pbio.3004026.ref022","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1002645","article-title":"Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships","volume":"8","author":"PP Pathare","year":"2012","journal-title":"PLoS Genet"},{"issue":"2","key":"pbio.3004026.ref023","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.tem.2008.11.002","article-title":"Fat synthesis and adiposity regulation in Caenorhabditis elegans","volume":"20","author":"JL Watts","year":"2009","journal-title":"Trends Endocrinol Metab"},{"key":"pbio.3004026.ref024","doi-asserted-by":"crossref","first-page":"4965","DOI":"10.1242\/jcs.00918","article-title":"Long chain polyunsaturated fatty acids are required for efficient neurotransmission in C. elegans","volume":"116","author":"GM Lesa","year":"2003","journal-title":"J Cell Sci"},{"issue":"11","key":"pbio.3004026.ref025","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.3390\/md11114544","article-title":"Antibacterial activity of long-chain polyunsaturated fatty acids against Propionibacterium acnes and Staphylococcus aureus","volume":"11","author":"AP Desbois","year":"2013","journal-title":"Mar Drugs"},{"issue":"6","key":"pbio.3004026.ref026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007893","article-title":"The fatty acid oleate is required for innate immune activation and pathogen defense in Caenorhabditis elegans","volume":"15","author":"SM Anderson","year":"2019","journal-title":"PLoS Pathog"},{"issue":"11","key":"pbio.3004026.ref027","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000273","article-title":"Gamma-linolenic and stearidonic acids are required for basal immunity in Caenorhabditis elegans through their effects on p38 MAP kinase activity","volume":"4","author":"M Nandakumar","year":"2008","journal-title":"PLoS Genet"},{"issue":"5","key":"pbio.3004026.ref028","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00430-023-00777-6","article-title":"Eicosapentaenoic acid influences the pathogenesis of Candida albicans in Caenorhabditis elegans via inhibition of hyphal formation and stimulation of the host immune response","volume":"212","author":"NZ Mokoena","year":"2023","journal-title":"Med Microbiol Immunol"},{"issue":"9","key":"pbio.3004026.ref029","doi-asserted-by":"crossref","first-page":"5854","DOI":"10.1073\/pnas.092064799","article-title":"Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans","volume":"99","author":"JL Watts","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"81","key":"pbio.3004026.ref030","first-page":"50879","article-title":"Dietary supplementation of polyunsaturated fatty acids in Caenorhabditis elegans","author":"ML Deline","year":"2013","journal-title":"J Vis Exp"},{"issue":"6810","key":"pbio.3004026.ref031","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/35042517","article-title":"Functional genomic analysis of C. elegans chromosome I by systematic RNA interference","volume":"408","author":"AG Fraser","year":"2000","journal-title":"Nature"},{"issue":"1","key":"pbio.3004026.ref032","doi-asserted-by":"crossref","DOI":"10.1016\/j.devcel.2019.02.001","article-title":"Microbial colonization activates an immune fight-and-flight response via neuroendocrine signaling","volume":"49","author":"J Singh","year":"2019","journal-title":"Dev Cell"},{"issue":"45","key":"pbio.3004026.ref033","doi-asserted-by":"crossref","first-page":"17469","DOI":"10.1073\/pnas.0809527105","article-title":"Role for beta-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions","volume":"105","author":"JE Irazoqui","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pbio.3004026.ref034","doi-asserted-by":"crossref","first-page":"111575","DOI":"10.1016\/j.celrep.2022.111575","article-title":"Cholinergic receptor-Wnt pathway controls immune activation by sensing intestinal dysfunction","volume":"41","author":"J Ren","year":"2022","journal-title":"Cell Rep"},{"key":"pbio.3004026.ref035","first-page":"367","article-title":"Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network","volume":"6","author":"HE Arda","year":"2010","journal-title":"Mol Syst Biol"},{"issue":"2","key":"pbio.3004026.ref036","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2018.12.064","article-title":"A persistence detector for metabolic network rewiring in an animal","volume":"26","author":"JT Bulcha","year":"2019","journal-title":"Cell Rep"},{"issue":"7378","key":"pbio.3004026.ref037","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nature10643","article-title":"Natural polymorphisms in C. elegans HECW-1 E3 ligase affect pathogen avoidance behaviour","volume":"480","author":"HC Chang","year":"2011","journal-title":"Nature"},{"issue":"7829","key":"pbio.3004026.ref038","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/s41586-020-2699-5","article-title":"C. elegans interprets bacterial non-coding RNAs to learn pathogenic avoidance","volume":"586","author":"R Kaletsky","year":"2020","journal-title":"Nature"},{"key":"pbio.3004026.ref039","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1471-2164-8-27","article-title":"Insight into transcription factor gene duplication from Caenorhabditis elegans Promoterome-driven expression patterns","volume":"8","author":"JS Reece-Hoyes","year":"2007","journal-title":"BMC Genomics"},{"key":"pbio.3004026.ref040","doi-asserted-by":"crossref","first-page":"986","DOI":"10.3389\/fmicb.2018.00986","article-title":"Aerobic vitamin B(12) biosynthesis is essential for Pseudomonas aeruginosa class II ribonucleotide reductase activity during planktonic and biofilm growth","volume":"9","author":"A Crespo","year":"2018","journal-title":"Front Microbiol"},{"key":"pbio.3004026.ref041"},{"issue":"5","key":"pbio.3004026.ref042","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2003-4-5-p3","article-title":"DAVID: database for annotation, visualization, and integrated discovery","volume":"4","author":"G Dennis","year":"2003","journal-title":"Genome Biol"},{"issue":"1","key":"pbio.3004026.ref043","doi-asserted-by":"crossref","first-page":"4785","DOI":"10.1038\/s41467-025-60154-0","article-title":"Worm Perturb-Seq: massively parallel whole-animal RNAi and RNA-seq","volume":"16","author":"H Zhang","year":"2025","journal-title":"Nat Commun"},{"issue":"2","key":"pbio.3004026.ref044","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.cmet.2013.07.007","article-title":"The NHR-8 nuclear receptor regulates cholesterol and bile acid homeostasis in C. elegans","volume":"18","author":"DB Magner","year":"2013","journal-title":"Cell Metab"},{"issue":"12","key":"pbio.3004026.ref045","article-title":"Regulators of AWC-mediated olfactory plasticity in Caenorhabditis elegans","volume":"5","author":"DM O\u2019Halloran","year":"2009","journal-title":"PLoS Genet"},{"issue":"7","key":"pbio.3004026.ref046","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/nmeth.1463","article-title":"Enhanced neuronal RNAi in C. elegans using SID-1","volume":"7","author":"A Calixto","year":"2010","journal-title":"Nat Methods"},{"issue":"10","key":"pbio.3004026.ref047","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.cub.2012.04.011","article-title":"The Caenorhabditis elegans RDE-10\/RDE-11 complex regulates RNAi by promoting secondary siRNA amplification","volume":"22","author":"C Zhang","year":"2012","journal-title":"Curr Biol"},{"issue":"5","key":"pbio.3004026.ref048","doi-asserted-by":"crossref","DOI":"10.1152\/ajpcell.00284.2009","article-title":"Loss of the apical V-ATPase a-subunit VHA-6 prevents acidification of the intestinal lumen during a rhythmic behavior in C. elegans","volume":"297","author":"E Allman","year":"2009","journal-title":"Am J Physiol Cell Physiol"},{"issue":"4","key":"pbio.3004026.ref049","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.bbrc.2009.11.006","article-title":"Fatty-acid metabolism is involved in stress-resistance mechanisms of Caenorhabditis elegans","volume":"390","author":"M Horikawa","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"issue":"2","key":"pbio.3004026.ref050","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1080\/19490976.2019.1643674","article-title":"Links between the gut microbiota, metabolism, and host behavior","volume":"11","author":"CE Schretter","year":"2020","journal-title":"Gut Microbes"},{"key":"pbio.3004026.ref051","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1101\/gad.350745.123","article-title":"The steroid hormone ADIOL promotes learning by reducing neural kynurenic acid levels","volume":"37","author":"GA Lemieux","year":"2023","journal-title":"Genes Dev"},{"issue":"4","key":"pbio.3004026.ref052","article-title":"Peripheral peroxisomal beta-oxidation engages neuronal serotonin signaling to drive stress-induced aversive memory in C. elegans","volume":"43","author":"SH Tsai","year":"2024","journal-title":"Cell Rep"},{"issue":"10","key":"pbio.3004026.ref053","article-title":"Intercellular sphingolipid signaling mediates aversive learning in C. elegans","volume":"35","author":"Y-C Wu","year":"2025","journal-title":"Curr Biol"},{"issue":"7","key":"pbio.3004026.ref054","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/s43587-025-00873-7","article-title":"Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity","volume":"5","author":"S Zhou","year":"2025","journal-title":"Nat Aging"},{"issue":"6","key":"pbio.3004026.ref055","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1111\/j.1474-9726.2008.00435.x","article-title":"The DAF-2 insulin-like signaling pathway independently regulates aging and immunity in C. elegans","volume":"7","author":"EA Evans","year":"2008","journal-title":"Aging Cell"},{"issue":"5","key":"pbio.3004026.ref056","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/j.1474-9726.2009.00501.x","article-title":"Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1\/Nrf","volume":"8","author":"RP Oliveira","year":"2009","journal-title":"Aging Cell"},{"key":"pbio.3004026.ref057","first-page":"1","article-title":"n-3 PUFA and inflammation: from membrane to nucleus and from bench to bedside","author":"PC Calder","year":"2020","journal-title":"Proc Nutr Soc"},{"issue":"9","key":"pbio.3004026.ref058","doi-asserted-by":"crossref","first-page":"306","DOI":"10.3390\/biomedicines8090306","article-title":"The anti-inflammatory and antioxidant properties of n-3 PUFAs: their role in cardiovascular protection","volume":"8","author":"F Oppedisano","year":"2020","journal-title":"Biomedicines"},{"issue":"2","key":"pbio.3004026.ref059","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ydbio.2006.01.013","article-title":"Dietary manipulation implicates lipid signaling in the regulation of germ cell maintenance in C. elegans","volume":"292","author":"JL Watts","year":"2006","journal-title":"Dev Biol"},{"issue":"2","key":"pbio.3004026.ref060","first-page":"203","article-title":"The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems","volume":"28","author":"M Carabotti","year":"2015","journal-title":"Ann Gastroenterol"},{"issue":"13","key":"pbio.3004026.ref061","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2024.e34092","article-title":"Gut-brain axis: A cutting-edge approach to target neurological disorders and potential synbiotic application","volume":"10","author":"S Ashique","year":"2024","journal-title":"Heliyon"},{"issue":"1","key":"pbio.3004026.ref062","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/s41522-024-00610-9","article-title":"Unlocking gut-liver-brain axis communication metabolites: Energy metabolism, immunity and barriers","volume":"10","author":"X Sun","year":"2024","journal-title":"NPJ Biofilms Microbiomes"},{"issue":"6705","key":"pbio.3004026.ref063","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/27579","article-title":"Specific interference by ingested dsRNA","volume":"395","author":"L Timmons","year":"1998","journal-title":"Nature"},{"issue":"6","key":"pbio.3004026.ref064","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.celrep.2017.10.050","article-title":"Distinct roles of sensory neurons in mediating pathogen avoidance and neuropeptide-dependent immune regulation","volume":"21","author":"X Cao","year":"2017","journal-title":"Cell Rep"},{"issue":"3","key":"pbio.3004026.ref065","doi-asserted-by":"crossref","DOI":"10.1128\/mSystems.00043-16","article-title":"MPLEx: A robust and universal protocol for single-sample integrative proteomic, metabolomic, and lipidomic analyses","volume":"1","author":"ES Nakayasu","year":"2016","journal-title":"mSystems"},{"issue":"9","key":"pbio.3004026.ref066","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1021\/ac802689c","article-title":"MetaboliteDetector: Comprehensive analysis tool for targeted and nontargeted GC\/MS based metabolome analysis","volume":"81","author":"K Hiller","year":"2009","journal-title":"Anal Chem"},{"issue":"1","key":"pbio.3004026.ref067","doi-asserted-by":"crossref","first-page":"26","DOI":"10.4161\/worm.19564","article-title":"A method for measuring fatty acid oxidation in C. elegans","volume":"1","author":"IC Elle","year":"2012","journal-title":"Worm"}],"updated-by":[{"DOI":"10.1371\/journal.pbio.3004026","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000}}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3004026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:57:41Z","timestamp":1791482261000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3004026"}},"subtitle":[],"editor":[{"given":"Mark J","family":"Alkema","sequence":"first","affiliation":[{"name":"UMass Chan Medical School","place":["UNITED STATES OF AMERICA"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":67,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3004026","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]}}}