{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li Y"],"funding":["National Outstanding Youth Science Fund Project of National Natural Science Foundation of China"],"pagination":["426"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12647480"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["82(1)"],"pubmed_abstract":["The gut microbiota plays a pivotal role in modulating obesity pathogenesis, yet the molecular mechanisms underlying its protective effects remain elusive. In this study, we demonstrate that L-ornithine (L-orn), a metabolite produced by Lactobacillus, confers resistance against high-fat diet (HFD)-induced obesity in mice by modulating macrophage function through its downstream metabolites spermine (SPM) and spermidine (SPD). Mechanistically, SPM suppressed pro-inflammatory cytokine production in macrophages by inhibiting the NF-κB and Akt signaling pathways, while SPD activated Src kinase and upregulated indoleamine 2,3-dioxygenase 1 (IDO-1), thereby promoting the polarization of immunosuppressive IDO-1<sup>+</sup> macrophages. Clinically, circulating L-orn levels were inversely correlated "],"journal":["Cellular and molecular life sciences : CMLS"],"pubmed_title":["Gut microbiota L-ornithine promotes resistance to obesity through metabolites mediated immunosuppressive macrophages."],"pmcid":["PMC12647480"],"funding_grant_id":["91842302"],"pubmed_authors":["Liu Y","Li Y","Zhang Y","Gao Y","Yang R","Wang J"],"additional_accession":[]},"is_claimable":false,"name":"Gut microbiota L-ornithine promotes resistance to obesity through metabolites mediated immunosuppressive macrophages.","description":"The gut microbiota plays a pivotal role in modulating obesity pathogenesis, yet the molecular mechanisms underlying its protective effects remain elusive. In this study, we demonstrate that L-ornithine (L-orn), a metabolite produced by Lactobacillus, confers resistance against high-fat diet (HFD)-induced obesity in mice by modulating macrophage function through its downstream metabolites spermine (SPM) and spermidine (SPD). Mechanistically, SPM suppressed pro-inflammatory cytokine production in macrophages by inhibiting the NF-κB and Akt signaling pathways, while SPD activated Src kinase and upregulated indoleamine 2,3-dioxygenase 1 (IDO-1), thereby promoting the polarization of immunosuppressive IDO-1<sup>+</sup> macrophages. Clinically, circulating L-orn levels were inversely correlated ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T16:45:54.46Z","creation":"2026-05-18T03:13:13.265Z"},"accession":"S-EPMC12647480","cross_references":{"pubmed":["41291317"],"doi":["10.1007/s00018-025-05882-8"]}}