Probiotics, live microorganisms conferring health benefits, are increasingly used to manage gastrointestinal diseases like ulcerative colitis (UC). However, safety concerns, such as increased mortality and bloodstream infections, exist. Postbiotics, inanimate microorganisms or their components with health benefits, are proposed as safer alternatives. This study directly compared the effects of probiotics and postbiotics derived from *Bifidobacterium adolescentis* B8589 in a dextran sulfate sodium (DSS)-induced colitis mouse model. UC is a chronic inflammatory disease affecting the colon and rectum, with unclear etiology but a known link to gut microbiota dysbiosis. Probiotics have shown promise in attenuating UC symptoms and inflammation by modulating the gut microbiota, but postbiotics are also emerging as potential therapeutics. This research aimed to directly compare the efficacy and gut microbiota modulation of probiotics and postbiotics derived from the same strain in a preclinical UC model, providing information for future therapeutic strategies.

The paper reviews existing literature on the use of probiotics in managing ulcerative colitis and highlights the safety concerns associated with their use. It cites several studies demonstrating the beneficial effects of probiotics in various disease models. However, it also points out the potential risks, such as increased mortality and bloodstream infections observed in some clinical trials. The introduction of postbiotics as a safer alternative is discussed, along with evidence suggesting their comparable efficacy in managing gastrointestinal disorders. The literature review underscores the need for a direct comparison between probiotics and postbiotics to determine their relative effectiveness and safety.

The study used a DSS-induced colitis mouse model. Four groups of mice (n=7 per group) were used: Control (water + saline), DSS (DSS only), Postbiotic (DSS + postbiotics), and Probiotic (DSS + probiotics). Both probiotics and postbiotics were derived from *Bifidobacterium adolescentis* B8589. Mice received treatment for seven days after DSS induction. Body weight, disease activity index (DAI), and colon length were measured. Histopathological analysis was performed to assess colon inflammation. Fecal samples were collected for whole-metagenome shotgun sequencing to analyze gut microbiota composition and diversity (alpha and beta diversity). The HUMAnN2 pipeline was used to analyze metagenomic functional potential and metabolic pathways. Statistical analyses included Kruskal-Wallis, ANOVA, Adonis test, Wilcoxon rank-sum test, and Spearman's correlation analysis.

Both postbiotics and probiotics significantly ameliorated colitis symptoms, as indicated by lower histology scores compared to the DSS group (P < 0.05). However, there was no significant difference in body weight loss, DAI, or colon length between the treatment groups. Postbiotic treatment showed stronger effects on modulating fecal microbiota beta diversity compared to probiotic treatment. While alpha diversity was not significantly different between groups, PCoA analysis demonstrated a clear separation of the fecal microbiota structure between the Postbiotic and DSS groups, which was not observed between the Probiotic and DSS groups. At the species level, thirteen differential species were identified between the Postbiotic and DSS groups, compared to only six between the Probiotic and DSS groups. Both postbiotic and probiotic treatments modulated the functional potential of the gut microbiome, with more significant changes observed in the postbiotic group. Correlation analysis revealed divergent changes in associations between gut microbiota and metabolic pathways in the postbiotic and probiotic groups, highlighting the unique mechanisms of action of each treatment.

The findings demonstrate that both postbiotics and probiotics from *Bifidobacterium adolescentis* B8589 can alleviate DSS-induced colitis, but postbiotics exhibit a more pronounced effect on gut microbiota modulation. The lack of significant differences in body weight, DAI and colon length may be attributed to limitations of the chosen metrics or differences in the experimental design compared to other published studies. The stronger modulation of the gut microbiome by postbiotics suggests a more targeted and effective impact on the inflammatory process. The observed differences in microbiota composition and metabolic pathways between the postbiotic and probiotic groups underscore the unique mechanisms underlying their therapeutic effects. The safety advantages of postbiotics, including the reduced risk of transmission of antibiotic resistance genes and the avoidance of systemic infection, combined with their superior modulatory effects, position them as a promising alternative to probiotics in managing UC.

This study provides the first systematic comparison of probiotics and postbiotics from the same strain in a mouse colitis model. While both treatments showed efficacy, postbiotics demonstrated a stronger ability to modulate the gut microbiota and associated metabolic pathways. Given the safety advantages and superior efficacy, postbiotics are a promising therapeutic strategy for managing ulcerative colitis and other diseases. Future research should focus on the specific mechanisms of action of postbiotics and larger-scale preclinical and clinical studies to confirm these findings and guide clinical application.

The study used a relatively small sample size (n=7 per group), which may limit the generalizability of the findings. The exact mechanisms by which postbiotics exert their beneficial effects remain unclear. Although postbiotics are considered safer, the study did not provide direct experimental evidence to support this. Further investigation is needed to confirm the safety and efficacy of postbiotics in larger animal models and human clinical trials. The chosen metrics for evaluating colitis severity did not show significant differences between treatment groups. Uniform assessment criteria are needed to compare results across different studies.