Tight Junction Protein Expression-Inducing Probiotics Alleviate TNBS-Induced Cognitive Impairment with Colitis in Mice

Abstract

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.

Probiotics: mechanism of action, health benefits and their application in food industries

“…Probiotics also act as anti-microbial agents by producing substances; short chain fatty acids (SCFA), organic acids, hydrogen peroxide ( Ahire et al, 2021 ), and bacteriocins ( Fantinato et al, 2019 ) thus decreasing pathogenic bacteria in the gut. Moreover, probiotics improve the intestinal barrier function by stimulating the production of mucin proteins ( Chang et al, 2021 ), regulating the expression of tight junction proteins, including occluding and claudin 1, and regulating the immune response in the gut ( Bu et al, 2022 ; Ma et al, 2022 ).…”

Gut bacteria exacerbates TNBS-induced colitis and kidney injury through oxidative stress

“…To elucidate the mechanisms through which bacteria exacerbate TNBS-induced colitis and renal injury, we assessed the potential impacts of lipopolysaccharide LPS, a bacterial component known to be released post-TNBS administration [ [26] , [27] , [28] ] on TNBS-induced cell oxidation and injury in the cultured colon epithelial cell line, Caco-2. As demonstrated in Fig.…”

“…This thinking is supported by the fact that TNBS used for induction of colitis was dissolved in 50% ethanol, whereas ethanol has been reported to be able to increase serum LPS level derived from intestinal Gram-negative bacteria [ 34 ]. Indeed, TNBS-induced colitis was reported to be associated with a high level of serum LPS [ [26] , [27] , [28] ]. The serum LPS, translocated from the gut lumen into the systemic circulation via the damaged intestinal epithelial barrier, activates pro-inflammatory pathways like TLR4/NF-κB signaling, triggering immune cell recruitment/activation and oxidative burst exacerbation of injury [ 30 , 35 ].…”

Involvement of Gut Microbiota in SLE and Lupus Nephritis

“…The expression of tight junction protein can be induced by schisandrin C that crucial for intestinal barrier function [ 86 ]. Furthermore, probiotic such as Bifidobacterium longum NK219 , Lactococcus lactis NK209 , and Lactobacillus rhamnosus NK210 enhance tight junction protein, suppress the LPS production from gut bacteria and subsequently alleviate leaky gut condition in gut inflamed mice [ 87 ]. Hence, probiotic treatment with Bifidobacterium longum NK219 , Lactococcus lactis NK209 , and Lactobacillus rhamnosus NK210 are potential in leaky gut impairment of LN.…”