Guanidine grafted chitosan oligosaccharides polymers promoting GLUT-mediated gastrointestinal barrier transport for potentiating Fe3O4 mineralized probiotics in obesity treatment

Obesity has become a major public health and social concern due to economic development and rising living standards. Currently, obesity treatment modalities often associated with various side effects. Probiotics have significant effects in mitigating obesity and reducing lipid levels. As a gentle anti-obesity approach, oral probiotics hold promise, yet they are vulnerable to inactivation in the harsh gastrointestinal environment. To address this challenge, this study developed an innovative binary system of armored probiotics (LPIC) that integrates microbiotherapy and chemotherapy. Iron oxide nanoparticles (IONPs) were applied using a single-bacterium encapsulation technique to create a protective armor on the surface of Lactobacillus plantarum (LP). This process produced armored probiotics (LPI) that effectively shield the bacteria from degradation by gastric acid. To complete the system, guanidine grafted chitosan oligosaccharides polymers (CHG) was added to LPI to form LPIC, enabling the chemotherapy component for obesity treatment. The LPIC system offers dual benefits: the IONP armor significantly improves bacterial survival in simulated gastric fluid (up to 58.02 %), while CHG facilitates rapid absorption and exerts therapeutic effects in the gastrointestinal tract. In vivo, LPIC administration led to a reduction in adipose tissue weight to 0.59 and 0.73 times that of high-fat diet (HFD) and LPI-treated mice, respectively. This suggests that IONPs not only promote fat reduction but also enable the gradual release and absorption of LP in the intestine, allowing effective colonization and sustained anti-obesity benefits.