Lacticaseibacillus paracasei SX52-B Isolated from Centenarians' feces: Genomic Analysis and Hypoglycemic Activity Evaluation.

Probiotics have been reported to effectively modulate human glucose metabolism. Here, we aim to isolate and identify Lacticaseibacillus paracasei SX52-B (L. paracasei SX52-B) from the intestines of centenarians, investigate its hypoglycemic properties, and explore the potential molecular mechanisms through integration of genomic analysis. To evaluate the probiotic properties, L. paracasei SX52-B was subjected to growth characteristics, safety and functional tests. Whole-genome sequencing of L. paracasei SX52-B was performed to identify functional genes related to hypoglycemic properties. Genomic annotation was conducted by comparing against databases such as GO, COG, KEGG, and CAZy. Firstly, L. paracasei SX52-B exhibited great biosafety across a series of assays. It could survive in simulated gut microbiota juices, indicating significant tolerance to acidic conditions and bile salts. Moreover, L. paracasei SX52-B showed no hemolytic activity and exhibited antibiotic susceptibility within safe limits. In the acute oral toxicity test of mice, neither adverse reactions nor significant differences in organ indices were detected after they were fed different doses of L. paracasei SX52-B for 28 days. Genomic sequencing and analysis revealed that the genome size of SX52-B is 2,991,568 bp. Through functional annotations, relatively rare carbohydrate metabolism-related genes such as malX (maltose/glucose PTS system EIICB component), tpiA (triosephosphate isomerase) and E5.1.3.15 (glucose-6-phosphate 1-epimerase), were identified in L. paracasei SX52-B, which were rarely detected in common L. paracasei strains. These results suggest that L. paracasei SX52-B possesses distinct genomic features related to glucose-lowering pathways. On the other hand, the result of in vitro functional assay demonstrated that L. paracasei SX52-B exhibited a high α-amylase activity inhibition rate (94.67%) and favorable lipid-lowering capacity. The supernatant of L. paracasei SX52-B also exhibited significant antioxidant activity. To verify the hypoglycemic capacity of L. paracasei SX52-B in vivo, we employed a hyperglycemic zebrafish model. It is revealed that both supernatant and bacteria of L. paracasei SX52-B significantly reduced the glucose content in zebrafish (P < 0.001). The study findings highlight that L. paracasei SX52-B exhibits favorable probiotic properties and hypoglycemic capacity, holding promising potential for application in the development of functional hypoglycemic foods or pharmaceutical products.