Formulation-dependent kinetics of Lacticaseibacillus paracasei Zhang in mice

The relationship between gut microbiota and human health has become one of the focal point in medical research. Probiotics, which modulate the gut microbiome, hold considerable promise for both prophylaxis and therapeutic intervention. This requires deeper insights into the kinetic changes and molecular mechanisms upon probiotic entry into the body. In this study, we utilized advanced molecular imaging to delineate the in vivo kinetic dynamics of two Lacticaseibacillus paracasei Zhang (L. paracasei Zhang, LPZ) formulations: a liquid culture and a lyophilized powder. Our results provide new insights into the gastrointestinal transit and growth kinetics of the different probiotics formulations. Strikingly, the liquid LPZ achieved its peak growth phase within a relatively short period of 6 to 8 h post-ingestion, culminating in a 270- to 680-fold increase in residues at the 24th hour post-ingestion when compared to the lyophilized powder LPZ. Furthermore, during peak in vivo replication, LPZ enhanced gut microbial diversity and enriched beneficial commensal communities. Functionally, LPZ ingestion attenuated virulence factors while upregulating carbohydrate-active enzymes. Notably, LPZ significantly reduced xanthine levels, a metabolite associated with hyperuricemia, thereby providing a mechanistic basis for the observed relief from gout symptoms. This supports the mechanism of prior clinical findings and paves the way for future clinical trials and therapeutic use of LPZ and related probiotics.

The innovation of this study lies in visualizing the kinetic changes of two Lacticaseibacillus paracasei Zhang (L. paracasei Zhang, LPZ) formulations (a liquid culture and lyophilized powder) within the gastrointestinal tract. It was found that liquid LPZ proliferates in vivo with a higher retention rate. Furthermore, we also found that when liquid LPZ reaches its peak proliferation phase in vivo, it not only effectively promotes the proliferation of other beneficial bacteria and the production of their metabolites but also generates more carbohydrate-active enzymes while reducing virulence factors, thereby amplifying the functions of LPZ. Meanwhile, we observed that liquid LPZ significantly reduces the production of xanthine in vivo, indicating its potential to lower uric acid. In light of the aforementioned findings, we herein propose the concept of "probiotikinetics." These results provide new insights into the intake of LPZ, along with important evidence for its application in healthy populations.