Gut microbiota L-ornithine promotes resistance to obesity through metabolites mediated immunosuppressive macrophages.

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⁺ macrophages. Clinically, circulating L-orn levels were inversely correlated

SUBMITTER: Li Y 

PROVIDER: S-EPMC12647480 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature