Carbon dioxide enhances Akkermansia muciniphila fitness and anti-obesity efficacy in high-fat diet mice.

Numerous studies and clinical applications have underscored the therapeutic potential of the indigenous gut bacterium Akkermansia muciniphila in various diseases. However, our understanding of how Akkermansia muciniphila senses and responds to host gastrointestinal signals remains limited. Here, we demonstrate that A. muciniphila exhibits rapid growth, facilitated by its self-produced carbon dioxide (CO₂), with key enzymes such as glutamate decarboxylase, carbonic anhydrase, and pyruvate ferredoxin oxidoreductase playing pivotal roles. Additionally, we design a novel delivery system, comprising calcium carbonate, inulin, A. muciniphila, and sodium alginate, which enhances A. muciniphila growth and facilitates the expression of part probiotic genes in mice intestinal milieu. Notably, the administration of this delivery system induces weight loss in mice fed high-fat diets. Furthermore, we elucidate the significant impact of CO₂ on the composition and functional genes of the human gut microbiota, with genes encoding carbonic anhydrase and amino acid metabolism enzymes exhibiting heightened responsiveness. These findings reveal a novel mechanism by which gut commensal bacteria sense and respond to gaseous molecules, thereby promoting growth. Moreover, they suggest the potential for designing rational therapeutic strategies utilizing live bacterial delivery systems to enhance probiotic growth and ameliorate gut microbiota-related diseases.