Heat-Killed Lactiplantibacillus plantarum LRCC5314 Mitigates the Effects of Stress- Related Type 2 Diabetes in Mice via Gut Microbiome Modulation

The incidence of stress-related type 2 diabetes (stress-T2D), which is aggravated by physiological stress, is increasing annually. The effects of Lactobacillus, a key component of probiotics, have been widely studied in diabetes; however, studies on the effects of postbiotics are still limited. Here, we aimed to examine the mechanism through which heat-killed Lactiplantibacillus plantarum LRCC5314 (HK-LRCC5314) alleviates stress-T2D in a cold-induced stress-T2D C57BL/6 mouse model. HKLRCC5314 markedly decreased body weight gain, adipose tissue (neck, subcutaneous, and epididymal) weight, and fasting glucose levels. In the adipose tissue, mRNA expression levels of stress-T2D associated factors (NPY, Y2R, GLUT4, adiponectin, and leptin) and pro-inflammatory factors (TNF-alpha, IL-6, and CCL-2) were also altered. Furthermore, HK-LRCC5314 increased the abundance of Barnesiella, Alistipes, and butyrate-producing bacteria, including Akkermansia, in feces and decreased the abundance of Ruminococcus, Dorea, and Clostridium. Thus, these findings suggest that HK-LRCC5314 exerts protective effects against stress-T2D via gut microbiome modulation, suggesting its potential as a supplement for managing stress-T2D.