Anti-pathogenic properties of non-digestible oligosaccharides. The fight against bacterial pathogens and toxins.

Despite effective prevention and control efforts over the past few decades, infectious diseases continue to pose a serious threat to global public health, causing millions of deaths annually. Numerous antibiotics can treat bacterial infections. However, practically almost all antimicrobial drugs now have some level of resistance, creating a severe global health issue and the urgent and rapid development of antibiotic alternatives. It has been demonstrated that NDOs are significant inhibitors of the development of pathogenic infections. Several anti-pathogenic effects can be achieved by NDOs, depending on their type and structural characteristics. This thesis suggests that Non-digestible oligosaccharides (NDOs) may serve as an alternative to antibiotics in treating bacterial infections. In our studies we investigated the effects of NDOs (AOS, COS, FOS and GOS) on the defense against several common bacterial pathogens (E. coli, S. agalactia, S. aureus, and C. difficile) in different steps of the pathogenesis: bacterial growth, bacterial adhesion, biofilm formation, inflammation and bacterial toxin activity. Each of these NDOs had some unique potentials against particular pathogens. Likewise, COS can be described as a potent biofilm inhibitor against S. aureus, a strong inhibitor of shiga toxin binding to its receptor (Gb3), a great inhibitor of cytotoxicity and cytopathogenicity of TcdA, an effective anti-inflammatory agent against inflammation caused by E. coli with intestinal barrier-protective properties and an enhancer of human intestinal epithelial cell integrity. Besides, AOS can be defined as a powerful inhibitor of the growth of both GBS and E. coli, an effective inhibitor of the adhesion of E. coli to intestinal epithelial cells, a potent anti-inflammatory agent against inflammation induced by E. coli, and an effective mediator on TcdA's ability to disrupt the intestinal barrier. The knowledge about the antimicrobial strategies of NDOs was used to further investigate in combination therapy by combining NDO with antibiotics to increase bacterial sensitivity to specific antibiotics. Likewise, a combination of COS and clindamycin was successful in preventing the growth of a S. aureus biofilm, as was a combination of AOS and ampicillin in the case of E. coli growth. AOS and trimethoprim were also successful in treating GBS when combined. NDOs are a desirable weapon in the fight against pathogens and antibiotic resistance due to their variety of antibacterial capabilities and minimal reported adverse effects. Moreover, a healthy microbiota plays a vital role in infection prevention by inhibiting pathogenic bacteria and/or coordinating proper immune responses, therefore the effect of NDOs on promoting beneficial bacteria in the gut should not be ignored.