Abstract
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.