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

Yang Cai; Jos P M van Putten; Myrthe S Gilbert; Walter J J Gerrits; Gert Folkerts; Saskia Braber

doi:10.1016/j.biomaterials.2022.121461

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

Yang Cai
, Jos P M van Putten
, Myrthe S Gilbert
, Walter J J Gerrits
, Gert Folkerts
, Saskia Braber

Wageningen University & Research

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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-κB" 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.

Original language	English
Article number	121461
Pages (from-to)	1-18
Number of pages	18
Journal	Biomaterials
Volume	283
Early online date	5 Mar 2022
DOIs	https://doi.org/10.1016/j.biomaterials.2022.121461
Publication status	Published - Apr 2022

Bibliographical note

Funding Information:
The authors would like to thank Henk A. Schols for the discussions about the GOS structures. This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V. Cooperatie AVEBE U.A. DSM Food Specialties B.V. FrieslandCampina Nederland B.V. Nutrition Sciences N.V. VanDrie Holding N.V. and Sensus B.V. and allowances of The Netherlands Organisation for Scientific Research (No. ALWCC.2015.4). Research grant funding (No. 201608320245) was received from the China Scholarship Council for Y. Cai.

Funding Information:
The authors would like to thank Henk A. Schols for the discussions about the GOS structures. This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl ). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V., Cooperatie AVEBE U.A., DSM Food Specialties B.V., FrieslandCampina Nederland B.V., Nutrition Sciences N.V., VanDrie Holding N.V. and Sensus B.V., and allowances of The Netherlands Organisation for Scientific Research (No. ALWCC.2015.4). Research grant funding (No. 201608320245 ) was received from the China Scholarship Council for Y. Cai.

Publisher Copyright:
© 2022 The Authors

Keywords

Airway inflammation
Antibiotic adjuvant
Bactericidal effect
Carbohydrate-based biomaterials
Intranasal drug delivery
Respiratory pathogens

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Cite this

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title = "Galacto-oligosaccharides as an anti-bacterial and anti-invasive agent in lung infections",

abstract = "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-κB{"} 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.",

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AU - Gilbert, Myrthe S

AU - Gerrits, Walter J J

AU - Folkerts, Gert

AU - Braber, Saskia

N1 - Funding Information: The authors would like to thank Henk A. Schols for the discussions about the GOS structures. This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V. Cooperatie AVEBE U.A. DSM Food Specialties B.V. FrieslandCampina Nederland B.V. Nutrition Sciences N.V. VanDrie Holding N.V. and Sensus B.V. and allowances of The Netherlands Organisation for Scientific Research (No. ALWCC.2015.4). Research grant funding (No. 201608320245) was received from the China Scholarship Council for Y. Cai. Funding Information: The authors would like to thank Henk A. Schols for the discussions about the GOS structures. This research was performed in the public-private partnership 'CarboKinetics' coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl ). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V., Cooperatie AVEBE U.A., DSM Food Specialties B.V., FrieslandCampina Nederland B.V., Nutrition Sciences N.V., VanDrie Holding N.V. and Sensus B.V., and allowances of The Netherlands Organisation for Scientific Research (No. ALWCC.2015.4). Research grant funding (No. 201608320245 ) was received from the China Scholarship Council for Y. Cai. Publisher Copyright: © 2022 The Authors

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N2 - 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-κB" 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.

AB - 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-κB" 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.

KW - Airway inflammation

KW - Antibiotic adjuvant

KW - Bactericidal effect

KW - Carbohydrate-based biomaterials

KW - Intranasal drug delivery

KW - Respiratory pathogens

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JO - Biomaterials

JF - Biomaterials

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ER -

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

Abstract

Bibliographical note

Keywords

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