Enhancing immunity offers a versatile yet effective strategy for treating or preventing diseases. Here, we obtained a new polysaccharide (AFP-80) from Anoectochilus formosanus that unexpectedly stimulated immune systems without causing any detectable adverse effects. AFP-80 was applied to encapsulate Lactobacillus plantarum (LP), a probiotic with immunoregulatory properties, through bridging by Fe 3+ –tannic acid network (Fe–TA) to establish an oral immune enhancer (LP@Fe-TA@AFP-80). Upon oral administration, LP@Fe-TA@AFP-80 colonized intestines with high survival rates, aided by gastrointestinal stress-shielding and adhesive properties of AFP-80 and Fe–TA, respectively, leading to synergistic immuno-enhancing effects through combining AFP-80 and live LP. As a result, in immunocompromised mice, LP@Fe-TA@AFP-80 significantly renovated immune functions, which was deciphered to be closely associated with the rebalance of gut microbiota toward a profile with positively-immunoregulatory bacteria enriched as well as the involvement of peroxisome proliferators-activated receptor signaling pathway activation. Additionally, LP@Fe-TA@AFP-80 effectively treated cancer, e.g. , 4T1 breast and MC38 colon tumors, either alone or in combination with immune checkpoint blockade therapy, by remodeling tumor immune microenvironment and gut microbiota. Moreover, LP@Fe-TA@AFP-80 demonstrated excellent biocompatibility, as directly revealed by negligible biotoxicity even after 6 months of consecutive ingestion, highlighting its great potential to be implemented into people’s daily life for disease prevention. A novel oral immune enhancer with high biocompatibility, composed of polysaccharides and probiotics, effectively modulates gut microbiota, strengthens immunity, and remodels the tumor microenvironment to treat tumors.
Xie et al. (Thu,) studied this question.