Metabolic exchanges between strains in gut microbial communities shape their composition and interactions with the host. This study investigates the metabolic synergy between potential probiotic bacteria … and Saccharomyces boulardii, aiming to enhance anti-inflammatory effects within a multi-species probiotic community. By screening a collection of 85 potential probiotic bacterial strains, we identified two strains that demonstrated a synergistic relationship with S. boulardii in pairwise co-cultivation. Furthermore, we computationally predicted cooperative communities with symbiotic relationships between S. boulardii and these bacteria. Experimental validation of 28 communities highlighted the role of S. boulardii as a key player in microbial communities, significantly boosting the community’s cell number and production of anti-inflammatory effectors, thereby affirming its essential role in improving symbiotic dynamics. Based on our observation, one defined community significantly activated the aryl hydrocarbon receptor—a key regulator of immune response—280-fold more effectively than the community without S. boulardii. This study underscores the potential of microbial communities for the design of more effective probiotic formulations.