Improving fecal transplantation precision for enhanced maturation of intestinal function in germ-free mice through microencapsulation and probiotic intervention

BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a widely used treatment for various diseases. While previous efforts have focused on selecting "super donors", the precise modulation of donor microbiota to enhance FMT efficacy remains a critical challenge. This study aimed to develop strategies to modify donor microbiota to promote gastrointestinal development and maturation in germ-free mice. Probiotic Pediococcus pentosaceus Li05 (Li05) was used as gut microbiota modulator to establish a healthier donor fecal microbiota, and a microencapsulation method was applied to ensure high bacterial viability during gastrointestinal tract transition. RESULTS: Probiotic intervention initially altered the stability of the gut microbiota but eventually fostered a more complex bacterial interaction network and established a new equilibrium within 14 days. Transplantation of encapsulated Li05-modulated fecal microbiota significantly promoted epithelial development, improved barrier function, and altered the colonic transcriptome profile. These effects were found to be more dependent on the abundance of some bacterial genera instead of their co-occurrence network, and the key functional bacterial genera associated with these benefits were believed to be Parabacteroides, Parasutterella, Lachnoclostridium, Muribaculum and Desulfovibrio. Notably, both encapsulation and probiotic modulation played critical roles in enhancing the functional efficacy of these key bacterial genera, and the community composed of key functional bacteria demonstrated an antagonistic relationship with other bacterial communities. Moreover, encapsulated Li05-modulated fecal microbiota induced dramatical changes in host lipid metabolism, especially the bile acids and their derives. Sporobiota gained the function of promoting epithelium development gene expression only after Li05-modulation since high abundance of Lachnoclostridium was introduced. CONCLUSION: These findings underscore the importance of encapsulation and donor microbiota modulation in FMT and provide valuable strategies for improving transplantation precision and outcomes.