Cross-feeding-based rational design of a probiotic combination of Bacterides xylanisolvens and Clostridium butyricum therapy for metabolic diseases

reciprocated by providing pABA for folate biosynthesis. Animal gavage experiments showed that the two-strain combination LBP exhibited superior therapeutic efficacy against metabolic disorders in high-fat diet-induced obese (DIO) mice compared to either single-strain treatment. Further omics-based analyses revealed that the single-strain treatments exhibited distinct taxonomic preferences in modulating the gut microbiota, whereas the combination LBP achieved more balanced modulation to preserve taxonomic diversity to a greater extent, thereby enhancing the stability and resilience of the gut microbiome. Moreover, the two-strain combinations more effectively restored gut microbial functions by reducing disease-associated pathways and opportunistic pathogen abundance. This work demonstrates the development of new LBP therapy for metabolic diseases from cross-feeding microbial pairs which exerted better self-stability and robust efficacy in complex intestinal environments compared to conventional single-strain LBPs.