l -Malic Acid Potentiates Bifidobacterium breve Bb18 Tolerance and Synergistically Ameliorates Colitis via Gut Microbiota-Metabolite Modulation

This study investigated l-malic acid (l-MA) as a protectant enhancing Bifidobacterium breve Bb18 (Bb18) bile tolerance and its synergistic therapeutic efficacy against DSS-induced colitis in mice. In vitro, 0.4% l-MA optimally enhanced Bb18 tolerance to glycodeoxycholic acid (GDCA) by 52.3%, preserving membrane integrity, boosting energy metabolism, and upregulating bile salt efflux genes, thus promoting a multidimensional cellular adaptive response. In vivo, the combination of Bb18 and l-MA synergistically alleviated the colon length shortening by 20.1%, reduced inflammation, and restored gut barrier integrity. Critically, l-MA potentiated Bb18 colonization under inflammatory stress by 217.6%. Furthermore, the combination simultaneously modulated the gut microbiota and increased barrier-protective metabolites, mechanistically linked to inflammation resolution. These results establish l-MA as a protective synbiotic partner for Bb18, offering a novel combinatorial strategy for probiotic-enhanced colitis management.