Galacto-oligosaccharides as an anti-bacterial and anti-invasive agent in lung infections

Emerging antimicrobial resistance in infections asks for novel intervention strategies. Galacto-oligosaccharides (GOS) might be attractive alternatives to antibiotics due to their anti-inflammatory and anti-adhesive properties. Mannheimia haemolytica is one of the major Pasteurellaceae associated with bovine lung infections. Using M. haemolytica, we demonstrated that GOS have the capacity to reduce bacterial viability and can be used as adjuvant to improve antibiotic efficacy. Using M. haemolytica-treated primary bronchial epithelial cells (PBECs) of calves, we identified the anti-adhesive and anti-invasive activities of GOS. The observed inhibition of cytokine/chemokine release and the prevention of airway epithelial barrier dysfunction in M. haemolytica-treated PBECs by GOS might be related to the downregulation of toll-like receptor 4/nuclear factor-kappa B pathway and the anti-invasive and anti-adhesive properties of GOS. Particularly, GOS lowered lipopolysaccharides- but not flagellin-induced cytokine/chemokine release in calf and human airway epithelial cells. Finally, we performed in vivo experiments in calves and demonstrated for the first time that intranasal application of GOS can relieve lung infections/inflammation and lower M. haemolytica positivity in the lungs without affecting clinical performance. These findings not only shed light on the anti-inflammatory mechanisms of GOS during lung infections, but GOS might also be a promising anti-bacterial agent for preventing (lung) infections.

Automated summary

The emergence of antimicrobial resistance in infections has created a need for new intervention strategies. Galacto-oligosaccharides (GOS) show potential as an alternative to antibiotics due to their anti-inflammatory and anti-adhesive properties. Mannheimia haemolytica is a major bacteria associated with bovine lung infections, and the study demonstrates that GOS can reduce its viability and enhance the efficacy of antibiotics. GOS also exhibit anti-adhesive and anti-invasive activities in primary bronchial epithelial cells, which can be attributed to their downregulation of toll-like receptor 4/nuclear factor-kappa B pathway. Furthermore, GOS have been shown to relieve lung infections/inflammation and reduce M. haemolytica positivity in vivo without altering clinical performance. These findings highlight the anti-inflammatory mechanisms of GOS and its potential as a promising agent for preventing infections.