Bifidobacterium animalis ssp. lactis 420 and Cordyceps militaris Synergistically Modulate the Gut Microbiota by Increasing Mucin 2 Production

Background: Probiotics and medicine food homology are known to offer gentle approaches to prevent obesity, although it is difficult with such approaches to satisfy consumers’ requirements to lose weight quickly. The probiotic strain Bifidobacterium animalis ssp. lactis 420 (B420) and Cordyceps militaris synergistically prevented obesity and related disorders in high-fat diet (HFD)-fed mice. Methods: The synergistic effects correlated with improved gut integrity, diminished systemic inflammation, and enhanced glucose homeostasis. Gut microbiota analysis revealed that the bloom of the commensal Akkermansia muciniphila contributed to the synergistic effects by inducing a profound shift in HFD-induced gut microbiota disorder. Results: The bloom of A. muciniphila was significantly correlated with a boost in mucin 2 within the colon, achieved through increased goblet cell quantity and elevated mucin 2 expression. To reveal the collaborating pathway, we found that Cordyceps militaris did not promote the propagation of B420 in vitro or in vivo. Moreover, heat-killed B420 could not enhance the preventive efficacy of Cordyceps militaris against obesity caused by the HFD. Conclusions: The metabolites of live B420 and Cordyceps militaris-derived metabolites in the gut microbiota collaboratively promoted the production of mucin 2. Thus, our results reveal a mechanism by which a combination of probiotics and medicine food homology enhance their therapeutic effects against obesity.