Impact of non-digestible carbohydrates andprebiotics on immunity, infections, inflammationand vaccine responses: a systematic review ofevidence in healthy humans and a discussion ofmechanistic proposals

Prebiotics, particularly non-digestible carbohydrates NDCs), are increasingly recognized for their role in modulating immune responses in the gut, lungs, and urinary tract. This review systematically evaluates evidence from human studies on the effects of NDCs and prebiotics on immune markers, infection risk and severity, inflammation, and vaccine responses. Prebiotics such as inulin, galactooligosaccharides (GOS), and fructooligosaccharides (FOS) positively influence gut microbiota by promoting beneficial species like Bifidobacteria. They also enhance the production of short-chain fatty acids (SCFAs) like butyrate, which interact with immune cells via G-protein-coupled receptors, inducing anti-inflammatory effects. In addition to microbiota-mediated mechanisms, NDCs and prebiotics may directly affect immune and epithelial cells by interacting with pattern recognition receptors (PRRs), enhancing gut barrier function, and modulating immunity. A systematic review of human studies showed that prebiotics, including GOS, FOS, and 2′-fucosyllactose (2FL), reduced infections and increased IgA in healthy infants, while yeast β-glucan reduced respiratory infection symptoms in healthy adults. Yeast β-glucan and GOS supplementation resulted in improvements in NK cell activity. Some effects on vaccine efficacy were noted in young adults, but the overall impact of NDCs and prebiotics on vaccination and systemic inflammation was inconsistent. Further research is needed to clarify the mechanisms involved and to optimize health applications.