{
  "abstract": "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 Caenorhabditis elegans. 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 fat-3 inhibition, which elevates LA, enhances pathogen avoidance, whereas loss of LA synthesis by fat-2 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\nMounting an immune response is energetically costly, and so host defenses are often influenced by internal metabolic states. This study identifies a gut-brain signaling mechanism in C. elegans wherein intestinal NHR-68 coordinates fatty acid homeostasis to shape pathogen avoidance and molecular immune responses.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America",
    "Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, United States of America",
    "Department of Microbiology and Molecular Genetics, McGovern Medical School at UTHealth, Houston, Texas, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jie Ren"
    },
    {
      "affs": [
        1
      ],
      "name": "Yu Sang"
    },
    {
      "affs": [
        2
      ],
      "name": "Young-Mo Kim"
    },
    {
      "name": "Ernesto S. Nakayasu"
    },
    {
      "name": "Alejandro Aballay"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7dsjwca19tgfp.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pbio.3004026",
  "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004026",
  "id": "7dsjwca19tgfp",
  "issns": [
    "1545-7885"
  ],
  "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004026",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Invertebrate Immune Response Mechanisms"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Digestive system/Gastrointestinal tract"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Lipids/Lipid metabolism"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Metabolism/Lipid metabolism"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/RNA interference"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Epigenetics/RNA interference"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/RNA interference"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genetic interference/RNA interference"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune response"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens/Pseudomonas aeruginosa"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Bacteria/Pseudomonas/Pseudomonas aeruginosa"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Animals/Invertebrates/Nematoda/Caenorhabditis/Caenorhabditis elegans"
    ],
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      "plos",
      "/Biology and life sciences/Psychology/Behavior"
    ],
    [
      "plos",
      "/Biology and life sciences/Psychology/Behavior/Animal behavior"
    ],
    [
      "plos",
      "/Biology and life sciences/Zoology/Animal behavior"
    ],
    [
      "plos",
      "/Biology and life sciences/Zoology/Animals/Invertebrates/Nematoda/Caenorhabditis/Caenorhabditis elegans"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Digestive system/Gastrointestinal tract"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens/Pseudomonas aeruginosa"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Caenorhabditis elegans"
    ],
    [
      "plos",
      "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Caenorhabditis elegans"
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    [
      "plos",
      "/Research and analysis methods/Model organisms/Caenorhabditis elegans"
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    [
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  "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3004026&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-29",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/7dsjwca19tgfp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.1371/journal.pbio.3004026",
      "source": "plos",
      "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004026"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:genetics",
      "subfield": "genetics-genomics"
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    {
      "field": "biology",
      "origin": "plos:animal behavior",
      "subfield": "zoology-behaviour"
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    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
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  ],
  "title": "Intestinal lipid metabolism controls molecular and behavioral immunity through NHR-68 and gut–brain signaling in Caenorhabditis elegans",
  "title_text": "Intestinal lipid metabolism controls molecular and behavioral immunity through NHR-68 and gut–brain signaling in Caenorhabditis elegans",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/7dsjwca19tgfp",
  "venue": "PLOS Biology",
  "versions": []
}