Enhancements of symbiotic adhesion and antibiotic efficacy observed by the metabolic crosstalk within cell-bacteria cocultured on a microfluidic gut chip.

The gut cells and symbiotic bacteria play a critical role in maintaining gut health and influencing disease development, with metabolic interactions among its constituents warranting further investigation. In this study, we developed a cell-bacteria coculture system on a microfluidic gut chip to simulate the human gut microenvironment and performed multi-omics analyses to elucidate the metabolic crosstalk within the system. The results revealed that the coculture significantly enhances the adhesion and biofilm formation of symbiotic bacteria to gut epithelial cells through activation of the glucose-pyruvate-acetate metabolic cycle. This coculture promotes glucose consumption and acetate secretion while remaining resilient to antibiotics. Moreover, the coculture protected symbiotic bacterial biofilms from antibiotic-induced disruption, thereby enhancing colonization resistance and improving the efficacy of antibiotics against pathogens. Our findings highlight the importance of cell-bacteria interactions in driving the glucose-pyruvate-acetate metabolic cycle, enhancing symbiotic adhesion, and optimizing antibiotic efficacy.