Gut microbiota in chronic inflammation: the interplay with lipid mediators

The gut microbiota plays a fundamental role in maintaining host health by regulating immune function, epithelial barrier integrity, and metabolic homeostasis. Disruption of microbial community structure (also known as dysbiosis) and altered host-microbiota interactions can shift microbial composition and metabolite production, promote immune dysregulation, and contribute to the initiation and persistence of chronic inflammation. Eicosanoids, a class of signaling lipid mediators derived from arachidonic acid , are essential modulators of acute and chronic inflammatory responses. Emerging evidence highlights a bidirectional interplay between the microbiota and eicosanoid pathways as a hallmark of chronic inflammation. Microbial taxa and their metabolites regulate arachidonic acid availability, eicosanoid biosynthesis, and receptor signaling in host cells. In turn, host-derived eicosanoids shape the gut environment, influencing the gut microbiota and host health state. This self-reinforcing loop drives key features of chronic inflammatory diseases, including a shift toward pro-inflammatory eicosanoid profiles, a relative deficiency of anti-inflammatory or pro-resolving lipid mediators, and microbiota dysbiosis. In this review, we summarize recent advances in the mechanisms underpinning microbiota-eicosanoid crosstalk, outline its contribution to chronic inflammatory diseases, and discuss the therapeutic potential of targeting this bidirectional axis.