Enzyme-Triggered Microcapsules for Colon-Targeted Delivery of Lacticaseibacillus rhamnosus Improve Metabolic Parameters in an Obese Mouse Model.

Obesity is associated with numerous metabolic disorders, and identifying safe and effective strategies for obesity management remains an important research priority. In our previous research, we successfully developed a colon-targeted probiotics oral delivery system, AP_2.0, which showed potential for obesity intervention. In this study, Lacticaseibacillus rhamnosus (L. rhamnosus) was encapsulated within AP_2.0, and the formulation was tested in a mouse model of obesity. The oral administration of AP_2.0@ L. rhamnosus resulted in a 14.6% reduction in body weight gain and a 20% decrease in low-density lipoprotein cholesterol compared to the model group, paralleling the metabolic improvements observed with orlistat in this murine model. 16S rRNA sequencing revealed that oral administration of AP_2.0@L. rhamnosus increased the abundance of Streptococcus_acidominimus and Ruminococcaceae, whereas the Orlistat group showed an increase in Bifidobacterium, suggesting distinct gut microbiota modulation profiles associated with weight loss. In conclusion, AP_2.0@L. rhamnosus shows promise as a potential intervention for obesity management, although further preclinical and clinical validation is required.