Lactiplantibacillus plantarum GUANKE ameliorates influenza a virus-induced inflammation and lung barrier dysfunction through enhancing mitophagy and improving oxidative phosphorylation.

GUANKE supplementation significantly attenuated inflammatory cytokine secretion in IAV-infected mice.

• C57BL/6 murine models were used for in vivo experiments.
• GUANKE was administered at a dose of 5 × 10⁹ CFU/day.
• Inflammatory cytokine secretion was significantly reduced compared to IAV-infected controls.
• Both GUANKE and exogenous linoleic acid supplementation produced this anti-inflammatory effect.

GUANKE and linoleic acid counteracted virus-mediated downregulation of pulmonary barrier proteins.

• IAV infection caused downregulation of pulmonary barrier proteins, which was reversed by GUANKE treatment.
• Exogenous linoleic acid at 40 mg/kg similarly restored pulmonary barrier protein expression.
• Lung barrier dysfunction is described as a predominant complication of influenza virus infections.
• Both GUANKE supplementation and its metabolite linoleic acid were effective in counteracting barrier dysfunction.

Linoleic acid was identified as a key metabolite of GUANKE mediating its protective effects.

• Exogenous linoleic acid was supplemented at 40 mg/kg in experimental models.
• Linoleic acid recapitulated the protective effects of GUANKE against IAV-induced inflammation.
• Linoleic acid also restored pulmonary barrier protein levels similarly to the parent probiotic.
• The metabolite modulated mitochondrial quality control through mitophagy and OXPHOS restoration.

GUANKE and GUANKE-derived linoleic acid enhanced Parkin-dependent mitophagy in IAV-infected mice.

• Mechanistic profiling identified Parkin-dependent mitophagy as a key pathway modulated by GUANKE.
• Enhanced mitophagy was part of the mitochondrial quality control mechanism triggered by GUANKE treatment.
• Both GUANKE (5 × 10⁹ CFU/day) and linoleic acid (40 mg/kg) activated this pathway.
• Parkin-dependent mitophagy was coupled with restored mitochondrial oxidative phosphorylation capacity.

GUANKE and linoleic acid restored mitochondrial oxidative phosphorylation (OXPHOS) capacity in IAV-infected mice.

• IAV infection impaired mitochondrial oxidative phosphorylation, which was restored by GUANKE treatment.
• Restoration of OXPHOS capacity was part of the overall mitochondrial quality control improvement.
• Both the probiotic and its metabolite linoleic acid contributed to OXPHOS restoration.
• Restored OXPHOS was mechanistically linked to the protective effects against pulmonary damage.