Citation: Tight Junction Protein Expression-Inducing Probiotics Alleviate TNBS-Induced Cognitive Impairment with...

A leaky gut is closely connected with systemic inflammation and psychiatric disorder. The rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induces gut inflammation and cognitive function in mice. Therefore, we selected Bifidobacterium longum NK219, Lactococcus lactis NK209, and Lactobacillus rhamnosus NK210, which induced claudin-1 expression in TNBS- or lipopolysaccharide (LPS)-stimulated Caco-2 cells, from the fecal bacteria collection of humans and investigated their effects on cognitive function and systemic inflammatory immune response in TNBS-treated mice. The intrarectal injection of TNBS increased cognitive impairment-like behaviors in the novel object recognition and Y-maze tests, TNF-α, IL-1β, and IL-17 expression in the hippocampus and colon, and LPS level in the blood and feces, while the expression of hippocampal claudin-5 and colonic claudin-1 decreased. Oral administration of NK209, NK210, and NK219 singly or together decreased TNBS-impaired cognitive behaviors, TNF-α and IL-1β expression, NF-κB⁺Iba1⁺ cell and LPS⁺Iba1⁺ cell numbers in the hippocampus, and LPS level in the blood and feces, whereas BDNF⁺NeuN⁺ cell and claudin-5⁺ cell numbers and IL-10 expression increased. Furthermore, they suppressed TNBS-induced colon shortening and colonic TNF-α and IL-1β expression, while colonic IL-10 expression and mucin protein-2⁺ cell and claudin-1⁺ cell numbers expression increased. Of these, NK219 most strongly alleviated cognitive impairment and colitis. They additively alleviated cognitive impairment with colitis. Based on these findings, NK209, NK210, NK219, and their combinations may alleviate cognitive impairment with systemic inflammation by suppressing the absorption of gut bacterial products including LPS into the blood through the suppression of gut bacterial LPS production and alleviation of a leaky gut by increasing gut tight junction proteins and mucin-2 expression.