Optimizing Lactiplantibacillus plantarum viability in the gastrointestinal tract and its impact on gut microbiota–brain axis through zein microencapsulation

Abstract Evidence suggests that Lactiplantibacillus plantarum (LP) can positively influence gut microbiota, subsequently affecting brain function via the gut–brain axis. However, the oral administration of LP may subject it to damage from gastric acid. To address this issue, a microencapsulation system was developed to protect LP and enhance its viability in the gastrointestinal tract. In the study, zein‐microencapsulated LP (MLP) was prepared using the phase separation method. We found that the optimal conditions to encapsulate LP (9 log CFU/mL) were a zein concentration of 10 mg/mL and a zein‐to‐bacteria mass ratio of 5:1. Scanning electron microscopy and dynamic light scattering analysis demonstrated that MLP exhibited a microstructure with an approximate diameter of 4 µm. Findings also revealed that microencapsulation markedly improved the in vitro survival rate of LP compared to free cells and allowed for controlled release. Subsequent in vivo studies in mice showed that this encapsulation not only boosted the colonization of LP but also ameliorated the imbalance of gut microbiota associated with depression. An analysis of the intestinal microbiota in mice identified 13 genera that exhibited significant shifts in abundance due to the depressive states. The administration of MLP reversed these microbial changes, underscoring its therapeutic potential. Additionally, the study examined the expression of pro‐inflammatory cytokines. The administrated MLP was found to reverse the inflammation in both the intestine and hippocampus of mice with depression. Behavioral assessments in mouse models corroborated the efficacy of MLP in preventing depression, positioning it as a promising daily supplement.