Lacticaseibacillus paracasei NK112 mitigates Escherichia coli-induced depression and cognitive impairment in mice by regulating IL-6 expression and gut microbiota

The gut microbiota communicates with the brain through microbiota-gut-brain (MGB) and hypothalamus-pituitaryadrenal (HPA) axes and other pathways. Excessive expression of interleukin (IL)-6 is closely associated with the occurrence of the psychiatric disorders depression and dementia. Therefore, to understand whether IL-6 expressionsuppressing probiotics could alleviate psychiatric disorders, we isolated IL-6 expression-inhibiting Lacticaseibacillus paracasei (formerly Lactobacillus paracasei) NK112 from the human faecal bacteria strain collection (Neurobiota Research Center, Seoul, Korea) and examined its therapeutic effect for the depression and cognitive impairment in mice. C57 BL/6J mice with depression and cognitive impairment were prepared by exposure to Escherichia coli K1. Oral gavage of NK112 significantly alleviated K1-induced anxious, depressive, and memory-impaired behaviours in the elevated plus maze, tail-suspension and Y-maze tasks, IL-1 beta, IL-6, and tumour necrosis factor (TNF)-alpha expression, and nuclear factor kappa beta (NF-kappa B) activation in the hippocampus, while K1-suppressed brain-derived neurotrophic factor (BDNF) expression increased. Treatment with NK112 also improved K1-induced myeloperoxidase activity, IL-6 and TNF-alpha expression, and NF-kappa B activation in the colon and reduced K1-induced Proteobacteria population in the gut microbiota. Heat-killed NK112 and its lysate supernatant, and precipitate fractions also improved anxiety/depression, cognitive impairment, and colitis in mice. In conclusion, NK112, even if heat-killed or lysed, alleviated K1 stress-induced colitis, anxiety/depression, and cognitive impairment by suppressing IL-6, TNF-alpha, and BDNF expression through the regulation of gut microbiota and NF-kappa B activation.