Lily polysaccharide may mitigate radiation-induced pneumonitis by modulating the gut-lung axis and pulmonary signalingLily Polysaccharide May Help Manage Radiation-Induced Pneumonitis

Radiation-induced pneumonitis (RIP) is a common and severe complication of thoracic irradiation, for which effective clinical treatments remain limited. Lily polysaccharide (LP), a natural polysaccharide derived from Lilium bulbs, exhibits various biological activities, including anti-inflammatory and tissue-protective effects. However, following oral administration, LP is poorly absorbed from the gastrointestinal tract and thus cannot directly target the lungs. Drawing on the gut-lung axis (GLA) theory, we hypothesize that oral LP may alleviate RIP by remotely inhibiting abnormal activation of the pulmonary cGAS-STING-NLRP3 signaling axis through modulation of the gut microbiota (GM) and its metabolites. Nevertheless, current evidence supporting this hypothesis remains largely indirect. Whether LP metabolites directly inhibit the pulmonary cGAS-STING-NLRP3 pathway, and whether such inhibition is causally linked to changes in the GM, require validation in RIP models. Therefore, this paper systematically reviews the molecular mechanisms underlying RIP, the multi-target pharmacological activities of LP, and the cross-organ regulatory network of the GLA. It also identifies key gaps in current research and provides a theoretical framework for future in-depth investigations, including fecal microbiota transplantation, germ-free animal models, structure-activity relationship analyses, and clinical safety assessments.