Long-chain unsaturated fatty acids released during immune responses stimulate host-microbe trans-kingdom communication

Article Article scientifique Article Long-chain unsaturated fatty acids released during immune responses stimulate host-microbe trans-kingdom communication eng 2025-09-18 2025-10-08 author Czauderna Aleksander Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Centre for Inflammation Research, University of Geneva, Geneva, Switzerland. 949879 author Kulkarni Grishma Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Centre for Inflammation Research, University of Geneva, Geneva, Switzerland. 413506 Département de pathologie et immunologie (PATIM) author Bianchi Niccolo Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Centre for Inflammation Research, University of Geneva, Geneva, Switzerland. 417383 Département de pathologie et immunologie (PATIM) author Cheng Liqing Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Centre for Inflammation Research, University of Geneva, Geneva, Switzerland. 957079 Département de pathologie et immunologie (PATIM) author Sim Marissa Department of Molecular and Cellular Biology, University of Guelph, Guelph, Canada. author Realini Nicola R Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. author Gach Joanna Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Wrocław, Poland. author Caillon Aurélie Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Centre for Inflammation Research, University of Geneva, Geneva, Switzerland. 126300 Département de pathologie et immunologie (PATIM) author Kloehn Joachim Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 869011 Département de microbiologie et médecine moléculaire (MIMOL) author Lambeau Gérard Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 7275 Centre National de La Recherche Scientifique and Université Côte D'Azur, Inserm U1323, Valbonne, France. author Hausmann Annika Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. author Serra Stefano Istituto di Scienze e Tecnologie Chimiche "Giulio Natta," Consiglio Nazionale delle Ricerche (SCITEC-CNR), Milan, Italy. author Sorbara Matthew T Department of Molecular and Cellular Biology, University of Guelph, Guelph, Canada. author Becattini Simone 0000-0001-5985-0403 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Centre for Inflammation Research, University of Geneva, Geneva, Switzerland. Electronic address: simone.becattini@unige.ch. 949421 Département de pathologie et immunologie (PATIM) 1667-1685.e14 10.1016/j.chom.2025.08.011 40972570 1931-3128 https://www.sciencedirect.com/science/article/pii/S1931312825003373 Immune responses can significantly alter the structure and function of the gut microbiota, leading to rapid transcriptional and metabolic shifts in commensal microbes. However, the host mediators involved in this process and their effects on bacteria remain poorly elucidated. Here, using a flagellin injection model to induce immune activation, we identified unsaturated long-chain fatty acids (uLCFAs) as broad modulators that are released into the gut lumen and alter bacterial gene expression. Luminal release of uLCFAs is partially mediated by host phospholipases, including PLA2G5. In response to uLCFAs, commensals such as Blautia trigger the expression of ohyA, encoding oleate hydratase, which converts toxic uLCFAs to non-toxic hydroxy fatty acids with immunomodulatory properties. Remarkably, oral administration of uLCFAs to mice replicates many of the bacterial transcriptional changes induced by flagellin. This molecular loop underscores the sophisticated interactions between host and microbiota and sheds light on how immune responses affect gut commensal functions. Blautia Immune responses Long-chain unsaturated fatty acids Microbiota Oleate hydratase Transcriptomics Dewey 616.07 Dewey 616 Canadian Institutes of Health Research Swiss National Science Foundation Harnessing the interactions between gut microbiota and immune system 187018 CH Careers Swiss National Science Foundation lnvestigating a multidrug-resistant pathogen through the lens of T cell immunity 211235 CH Programmes Swiss National Science Foundation Bacterial molecular modulators of epithelial barrier function 223765 CH Careers 137 Département de pathologie et immunologie 21F 54 Département de microbiologie et médecine moléculaire 21B false 1340 Host-Microbe Interactions 1027 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282875 https://yareta.unige.ch/archives/b38108dd-039c-4dfc-8124-8358cec4b14e Cell host & microbe 33 10 f3b10c5a-1f75-4808-ad4d-9e2e13cbb9a0 Article (Published version) Public PIIS1931312825003373.pdf 18454101 application/pdf CC BY-4.0 5690e1237235b2044277a2324a15d08ddc25cf96cf00fa1e790316d28ede79e1 7aaf96bc-4bbb-4145-9543-d547af0acb67 Supplemental data Public 1-s2.0-S1931312825003373-mmc1.pdf 15667308 application/pdf 5d5cfc723ba3e29b82fa895f48c45c0fb473d6560c9bababea441c4039afb92a Vignette Public 1-s2.0-S1931312825003373-fx1.jpg 124393 image/png openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Long-chain unsaturated fatty acids released during immune responses stimulate host-microbe trans-kingdom communication	Cell host & microbe			2025	68	86

Archive ouverte UNIGE

Kulkarni, Grishma