Antibacterial and Immunomodulatory Effects of Limosilactobacillus reuteri LMG P-27481 and Resveratrol Relevant for the Control of Upper Respiratory Tract Pathobionts

Although most upper respiratory tract infections (URTIs) have a viral etiology, antibiotics are widely prescribed, thus contributing substantially to antimicrobial resistance. This study investigated the potential beneficial effects of a novel strain, Limosilactobacillus reuteri LMG P-27481, against major URT pathobionts (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae) with the aim of reducing or delaying antibiotic use. Antibacterial and immunomodulatory activities were evaluated using L. reuteri alone or combined with resveratrol, a natural compound with antiviral and anti-inflammatory properties. Both agents inhibited pathogen growth, while their combination showed additive antibacterial activity, particularly against Gram-negative bacteria. Antioxidant assays demonstrated significant antioxidant capacity for both agents, with enhanced effects in combination in NBT and ABTS assays but antagonistic in ORAC. Immune mediators (IL-6, IL-8, IL-1β, TNF-α, IL-25, IL-33, CCL17, CCL22) were assessed in epidermal, epithelial, and macrophage cell lines, together with epidermal integrity markers (Filaggrin, Loricrin, Involucrin) in a 3D reconstructed human skin model (EpiDermFTTM). L. reuteri, resveratrol, and their combination exerted cell-specific effects in the different models, modulating cytokine expression and production, and barrier integrity. Our findings support the potential efficacy of oral L. reuteri LMG P-27481 plus resveratrol in URTIs.