Oligosaccharides to suppress respiratory infections: A translational approach

The studies described in this thesis have investigated the anti-inflammatory effects and possible mechanisms of non-digestible oligosaccharides (NDOs), including galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS), in respiratory infections in calves naturally exposed to respiratory pathogens, with a possible translation to human respiratory infections. An in vivo model in calves and in vitro models in primary bronchial epithelial cells obtained from calves and human lung epithelial cells were used to investigate the potential effects and mechanisms of GOS and FOS. Anti-inflammatory effects of GOS and FOS observed in vitro were compared with the effects on inflammatory markers in the airway and blood of calves fed with these NDOs. The main mechanisms related to anti-inflammatory effects of GOS and FOS derived from the present in vitro studies include 1) the anti-bacterial effect of GOS at high concentrations on respiratory pathogens (e.g., Mannheimia haemolytica and Mycoplasma pneumoniae), 2) possible interference with Toll-like receptor 4 proinflammatory signaling and inhibition of oxidative stress by GOS at low concentrations, and 3) possible interference with Toll-like receptor 5 proinflammatory signaling and protection of airway epithelial barrier function by FOS. Due to these mechanisms, (oral or intranasal) GOS and FOS (partly) relieved lung infections and suppressed airway and systemic inflammation in calves. Finally, these results might contribute to reducing the future use of antibiotics in livestock species and humans and need to be incorporated into the evolving knowledge of microbiota-dependent or -independent effects of NDOs.