Impact of non-digestible carbohydrates and prebiotics on immunity, infections, inflammation and vaccine responses: a systematic review of evidence in healthy humans and a discussion of mechanistic proposals
There is growing interest in prebiotics, specifically non-digestible carbohydrates (NDCs), for their role in modulating the immune response in the gut, lungs, and urinary tract. Prebiotics such as inulin, galactooligosaccharides (GOS), and fructooligosaccharides (FOS), can positively influence the gut microbiota by promoting beneficial bacteria like Bifidobacteria. They also support the production of short-chain fatty acids, which can interact with immune cells and induce anti-inflammatory effects. Furthermore, prebiotics and NDCs may directly interact with immune and epithelial cell receptors, enhancing gut barrier function and modulating immunity. This review systemically assessed the scientific evidence from human studies on the effects of prebiotics and NDCs on markers of immunity and inflammation, infection risk and severity, and the response to vaccination in healthy individuals. A comprehensive search of PubMed, Scopus, and Embase was conducted to identify randomized, controlled trials (RCTs) published up to January 28th, 2025. The search results retrieved 40 RCTs, which demonstrated that, while effects on vaccine responses and systemic inflammation were inconsistent, prebiotics such as GOS, FOS, inulin, and beta-glucans improved the immune function, particularly by increasing immunoglobulin A (IgA) levels and enhancing natural killer (NK) cell activity. Notably, the studies reported variable results across different age groups. Overall, the evidence suggests that prebiotics may support immune health and reduce infection risks; however, further research is needed to explore population-specific and age-specific effects, identify optimal types, doses, and their exact mechanisms of action.
Key takeaways:
- This systematic review included 40 RCTs that evaluated the effects of prebiotics and NDCs on immune function, infections, inflammation, and vaccine responses in healthy individuals.
- Prebiotics, such as GOS, FOS, inulin, and beta-glucans, showed positive effects on immune markers, including IgA and NK cell activity.
- Evidence for the impact of prebiotics on systemic inflammation and vaccine responses is inconsistent.
- Future studies are needed to determine optimal types, doses, and target populations.
Access the study: https://pubmed.ncbi.nlm.nih.gov/40516031/
Reference: Arioz Tunc, H., Calder, P. C., Cait, A., Dodd, G. F., Gasaly Retamal, N. Y. I., Guillemet, D., James, D., Korzeniowski, K. J., Lubkowska, A., Meynier, A., Ratajczak, W., Respondek, F., Thabuis, C., Vaughan, E. E., Venlet, N., Walton, G., Gasser, O., & de Vos, P. (2025). Impact of non-digestible carbohydrates and prebiotics on immunity, infections, inflammation and vaccine responses: a systematic review of evidence in healthy humans and a discussion of mechanistic proposals. Critical reviews in food science and nutrition, 1–74. Advance online publication. https://doi.org/10.1080/10408398.2025.2514700.
Differential effects of inulin and fructooligosaccharides on gut microbiota composition and glycemic metabolism in overweight/obese and healthy individuals: a randomized, double-blind clinical trial
Innovative strategies are needed to address the global rise in metabolic diseases. Prebiotics make a promising strategy for managing metabolic diseases by modulating the gut microbiota; however, clinical evidence regarding their effects on glycemic metabolism remains inconsistent. This randomized, double-blind study examined the impact of two commonly used prebiotics, inulin and FOS, on glycemic metabolism in overweight/obese and healthy adults. A total of 131 participants were randomized to receive 15 g/day of inulin (n=44), FOS (n=43), or maltodextrin (placebo, n=44) for four weeks. Pre- and post-intervention blood and fecal samples were analyzed to assess fasting insulin, glucose tolerance, homocysteine levels, and gut microbiota composition. Among overweight/obese individuals, inulin supplementation led to significant reduction in glucose levels at the 1-hour and 2-hour timepoints during the oral glucose tolerance test, a significant increase in fasting insulin, and a reduction in homocysteine levels. These effects were not observed in healthy participants or in the FOS group, aside from a significant reduction in homocysteine levels with FOS. Inulin also modulated the gut microbiota, notably reducing Ruminococcus abundance by 72%, which correlated with improved glycemic markers, along with a significant decrease in propionate levels in both weight groups. The study findings highlight the importance of population-specific prebiotic interventions, suggesting that inulin may be more beneficial for managing glycemic dysregulation in overweight/obese individuals, while FOS may support through homocysteine reduction. Future research should explore the long-term effects and strain-specific responses to further optimize prebiotic strategies.
Key takeaways:
- Prebiotics such as inulin and FOS may be utilized as promising intervention strategies to help manage the global rise of metabolic diseases.
- This study compared the effects of inulin and FOS on glycemic metabolism and gut microbiota in overweight/obese and healthy normal-weight adults.
- The study showed the different mechanistic pathways of inulin and FOS across different population cohorts. While inulin significantly improved glycemic markers such as fasting insulin and homocysteine levels and modulated the gut microbiota in overweight/obese participants, FOS lowered homocysteine levels in both weight groups.
- The study results support the targeted use of prebiotics for personalized metabolic care.
Access the study: https://pubmed.ncbi.nlm.nih.gov/40598275/
Reference: Li, J., Liu, F., Luo, Y., Wijeyesekera, A., Wang, S., Chen, X., Lv, Y., Jin, J., Sheng, H., Wang, G., Wei, Y., Li, Z., Chen, M., & Zhou, H. (2025). Differential effects of inulin and fructooligosaccharides on gut microbiota composition and glycemic metabolism in overweight/obese and healthy individuals: a randomized, double-blind clinical trial. BMC medicine, 23(1), 372. https://doi.org/10.1186/s12916-025-04189-6.
Effects of probiotics, prebiotics, and synbiotics on sarcopenia parameters in older adults: a systematic review and meta-analysis of randomized controlled trials
Sarcopenia is a multifactorial, progressive, and generalized musculoskeletal disorder associated with aging. The European Working Group on Sarcopenia in Older People defines sarcopenia as low muscle strength, low muscle quantity or quality, and low physical performance. Emerging evidence suggests that the gut microbiota may be involved in the onset of sarcopenia in older adults. Nutritional strategies, such as probiotics, prebiotics, and synbiotics, can modify the microbiota composition, supporting a healthy flora to obtain optimal health benefits. This systematic review and meta-analysis aimed to determine the optimal prebiotic, probiotic, and/or synbiotic interventions for sarcopenia management in older adults, focussing on their effects on muscle strength, muscle mass, and physical performance and function. The search was conducted using three databases, including Medline/PubMed, Cochrane Library, and Scopus. Other sources, such as references included in the identified studies from the databases, were also used. Limiting the search time between 2000 and 2023, eight RCTs were included in the systematic review and four were included in the meta-analysis. The study found that probiotic-based nutritional strategies significantly improved muscle strength and physical function. However, applying sensitivity analysis on the probiotic studies for muscle strength led to a loss of statistical significance and effectiveness. Limited studies are available on prebiotics and synbiotics, with additional studies needed to elucidate their effects on sarcopenia parameters. Overall, this meta-analysis reported heterogeneity in sample sizes across studies, influencing the reliability of the results.
Key takeaways:
- There is limited evidence to determine which supplementation – probiotics, prebiotics, or synbiotics – is most effective to improve sarcopenia parameters.
- This systematic review and meta-analysis revealed that probiotic supplementation can effectively improve muscle strength and physical function.
- Future research should focus on robust study designs with larger sample sizes, different bacterial strains, doses, dose durations, and control for variables to better understand the effects of biotics on the gut-muscle axis.
Access the study: https://pubmed.ncbi.nlm.nih.gov/39405177/
Reference: Besora-Moreno, M., Llauradó, E., Valls, R. M., Pedret, A., & Solà, R. (2025). Effects of Probiotics, Prebiotics, and Synbiotics on Sarcopenia Parameters in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrition reviews, 83(7), e1693–e1708. https://doi.org/10.1093/nutrit/nuae145.
Effects of prebiotics and phytochemicals on serum trimethylamine N-oxide reduction and gut microbiota: a systematic review and meta-analysis
Serum trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite linked to various health conditions, including cardiovascular disease, kidney dysfunction, and mortality. Due to its health implications, regulating TMAO levels through non-pharmacological interventions such as prebiotics and phytochemicals has garnered significant interest. However, the efficacy of these interventions is inconsistent across the existing evidence. This systemic review and meta-analysis evaluated the effects of prebiotics and phytochemicals on serum TMAO levels, its precursor trimethylamine (TMA), and gut microbiota composition. A total of 41 studies, including both animal studies and human clinical trials, retrieved from PubMed, Web of Science, Embase, and Cochrane Library were considered in the analysis. The results revealed that prebiotics and phytochemicals significantly reduced serum TMAO levels in both animals and humans. TMA levels in animals were also significantly lowered. The interventions significantly altered both alpha- and beta-diversity of the gut microbiota, particularly Akkermansia and Bifidobacterium genera. However, substantial heterogeneity and publication bias were noted, suggesting caution when interpreting the findings. Altogether, this systemic review and meta-analysis supports the potential of phytochemical and prebiotic interventions for reducing serum TMAO levels and improving gut health. Future research should focus on high-quality, standardized clinical trials to confirm these effects and enhance translational relevance from animal to human data.
Key takeaways:
- This study reviewed existing evidence on the therapeutic potential of microbiota-targeted dietary strategies like phytochemicals and prebiotics for TMAO reduction.
- Further high-quality, standardized trials are needed to support the translational relevance of animal findings to human applications.
Access to the study: https://pubmed.ncbi.nlm.nih.gov/40634923/
Reference: Wan, Z. W., Zheng, L. J., Huang, Y. F., Xie, J. W., Li, J. L., & Chen, Y. R. (2025). Effects of prebiotics and phytochemicals on serum trimethylamine N-oxide reduction and gut microbiota: a systematic review and meta-analysis. Journal of translational medicine, 23(1), 759. https://doi.org/10.1186/s12967-025-06806-7.
