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One promising approach to address these challenges is the dietary supplementation of non-digestible oligosaccharides (NDOs). NDOs, including human milk oligosaccharides (HMOs), play a vital role in shaping and sustaining a healthy gut microbiota. Beyond stimulating the growth and activity of beneficial gut bacteria, NDOs can also interact directly with pathogenic bacteria and viruses. Their antiviral and antibacterial properties arise from their unique interactions with pathogens and their ability to modulate the host\u2019s immune system. NDOs can function as decoy receptors, inhibit pathogen growth, bind to bacterial toxins, stimulate the host immune response, exhibit anti-biofilm properties, and enhance barrier protection. However, a notable gap exists in the comprehensive assessment of in vivo and clinical data on this topic. This review aims to provide an in-depth overview of the in vivo evidence related to the antiviral and antibacterial effects of various NDOs and HMOs, with a focus on discussing their possible mechanisms of action.<\/jats:p>","DOI":"10.3390\/nu17061068","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T06:10:53Z","timestamp":1742364653000},"page":"1068","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In Vivo Evidence on the Emerging Potential of Non-Digestible Oligosaccharides as Therapeutic Agents in Bacterial and Viral Infections"],"prefix":"10.3390","volume":"17","author":[{"given":"Amirmohammad","family":"Afsharnia","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CB Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-9781","authenticated-orcid":false,"given":"Yang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen","family":"Nauta","sequence":"additional","affiliation":[{"name":"FrieslandCampina, 3818 LE Amersfoort, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Groeneveld","sequence":"additional","affiliation":[{"name":"FrieslandCampina, 3818 LE Amersfoort, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-2192","authenticated-orcid":false,"given":"Gert","family":"Folkerts","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CB Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7464-7232","authenticated-orcid":false,"given":"Marc M. 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