Stable colonization of Akkermansia muciniphila educates host intestinal microecology and immunity to battle against inflammatory intestinal diseases

Abstract

AbstractGut microbial preparations are widely used in treating intestinal diseases but show mixed success. In this study, we found that the therapeutic efficacy ofA. muciniphilafor dextran sodium sulfate (DSS)-induced colitis as well as intestinal radiation toxicity was ~50%, and mice experiencing a positive prognosis harbored a high frequency ofA. muciniphilain the gastrointestinal (GI) tract. Stable GI colonization ofA. muciniphilaelicited more profound shifts in the gut microbial community structure of hosts. Coexisting withA. muciniphilafacilitated proliferation and reprogrammed the gene expression profile ofLactobacillus murinus, a classic probiotic that overtly responded toA. muciniphilaaddition in a time-dependent manner. Then, a magnetic-drove, mannose-loaded nanophase material was designed and linked to the surface ofA. muciniphila. The modifiedA. muciniphilaexhibited enhancements in inflammation targeting and intestinal colonization under an external magnetic field, elevating the positive-response rate and therapeutic efficacy against intestinal diseases. However, the unlinked cocktail containingA. muciniphilaand the delivery system only induced negligible improvement of therapeutic efficacy. Importantly, heat-inactivatedA. muciniphilalost therapeutic effects on DSS-induced colitis and was even retained in the GI tract for a long time. Further investigations revealed that the modifiedA. muciniphilawas able to drive M2 macrophage polarization by upregulating the protein level of IL-4 at inflammatory loci. Together, our findings demonstrate that stable colonization of liveA. muciniphilaat lesion sites is essential for its anti-inflammatory function.