Metabolomic analysis of cooperative adaptation between Co-cultured Lacticaseibacillus casei Zhang and Lactiplantibacillus plantarum P8

Microbial secondary metabolites have long been considered as potential sources of natural active molecules due to their rich chemical diversity and extensive biological activities. Increasing evidence shows that coculture from probiotic strains had synergistic effect promoting the production of bioactive molecules, and secondary metabolites that had higher stability and/or functional performance. The purpose of this study was to explore the interaction between Lacticaseibacillus casei Zhang (LcZ) and Lactiplantibacillus plantarum P8 (P8) during co-culture using non-targeted metabonomics approach. Results showed stronger growth in the LcZ and P8 co-culture (LcZ + P8) compared with either bacterium alone. Multivariate analysis revealed that significant differences in metabolic profiles between strains, and by and within the same strain at different growth stages. In addition, the alteration of cell and media metabolites during cell growth was strongly associated with energy production. Moreover, some new bioactive substances and substances with higher expression levels that might have beneficial effect on human health were identified in LcZ + P8.This is the first study to systematically identify a symbiotic interaction of metabolites in an ecosystem established by P8 and LcZ. The results provide novel insight into the system-level cooperative adaptation between strains and have implications for the further development of microbial natural products.