Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 Alleviate Escherichia coli-Induced depression and Gut Dysbiosis in Mice

Abstract

Excessive exposure to stressors such as social defeat, immobilization, antibacterials, and pathogen infection stimulate the release of adrenal hormones noradrenaline, adrenaline, and glucocorticoids through the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the secretion of proinflammatory cytokines IL-6 and TNFα. This results in the occurrence of psychiatric disorders, colitis, and gut dysbiosis [1, 2]. Treatment with 2,4,6trinitrobenzenesulfonic acid (TNBS), a colitis inducer, causes colitis, gut dysbiosis, and cognitive impairment in mice [3]. Oral gavage of ampicillin causes gut dysbiosis, colitis, and anxiety/depression in mice [4]. Infection with pathogens such as TNBS-induced Escherichia coli and ampicillin-induced Klebsiella oxytoca in the intestine of mice causes colitis with psychiatric disorders, including anxiety/depression and memory impairment, through the activation of the microbiota-gut-brain (MGB) axis [3-5]. However, Lactobacillus mucosae NK41 alleviates E. coli K1 (K1)-induced cognitive impairment, depression, and colitis in mice by the amelioration of gut dysbiosis [5]. Gut microbiota consist of > 1,000 bacterial species in humans and animals [6] and display a variety of physiological functions such as modulation of the host's immune and nervous systems and defense against pathogen attacks [6, 7]. However, the induction of gut opportunistic E. coli K1 by immobilization stress (IS) causes colitis and psychiatric disorders [5, 8]. Bifidobacterium adolescentis IM38 mitigates anxiety in IS-treated mice [9]. Lactobacillus reuteri NK33 (NK33), B. adolescentis NK98 (NK98), and their (1:1) mixture were also reported to alleviate IS-induced anxiety/depression in mice [10]. However, at present, the gut microbiota-mediated inhibitory mechanism of probiotics NK33 and NK98 against anxiety/depression remains unclear. Therefore, in the present study, we examined the effects of NK33, NK98, and their mixtures (1:1, 4:1, and 9:1) on K1-induced gut dysbiosis, colitis, and depression in mice. Male C57BL/6 mice (5 weeks of age; 19-21 g in weight) were supplied by Koatech Inc. (Republic of Korea). The animals were maintained under controlled condition (temperature, 20 ± 2°C; humidity, 50 ± 10%; light-dark cycle, 12 h). The mice received standard laboratory chow with tap water ad libitum. All animal experiments were approved by the Institutional Animal Care and Use Committee of the University (IACC No. KUASP(SE)-19-152) and were performed according to the University Guide for Laboratory Animal Care and Usage. NK33 and NK98 were cultured in MRS broth (BD, USA) for probiotics and K1 was cultured in the tryptic soy broth (BD). Cultured bacteria were centrifuged (5,000 g, 20 min, 4 o C) and suspended in 1% maltose. The mice with K1-induced depression were prepared following a previous report [8]. To evaluate the effects of NK33 and NK98 on the occurrence of depression, the mice were randomly divided into seven groups (CON, EC, Lactobacillus reuteri NK33 (NK33) and Bifidobacterium adolescentis NK98 (NK98...

Oregano Essential Oils Mediated Intestinal Microbiota and Metabolites and Improved Growth Performance and Intestinal Barrier Function in Sheep

“…Lactobacillus reuteri NK33 could alleviate gut inflammation by suppressing the expression of TNF-a and IL-6 through activation of the NF-kB signaling pathway (51). Similarly, we observed that LR reduced expression of IL-6.…”

“…In this study, OEO supplementation reduce gene expression of the NF-κB p65 , TLR-4 and pro-inflammatory cytokine IL-6 , indicating that OEO could reduce the production of cytokines via suppressing inflammatory signaling pathway expression in the ileum. Lactobacillus reuteri NK33 could alleviate gut inflammation by suppressing the expression of TNF-α and IL-6 through activation of the NF-κB signaling pathway ( 51 ). Similarly, we observed that LR reduced expression of IL-6 .…”

The Alleviation of Gut Microbiota-Induced Depression and Colitis in Mice by Anti-Inflammatory Probiotics NK151, NK173, and NK175

“…Probiotics, including Lactobacilli and Bifidobacteria, alleviate gut dysbiosis [ 17 ], immune imbalance [ 18 ], inflammation [ 19 ], depression [ 20 ], and memory impairment [ 21 ]. Bifidobacterium adolescentis IM38 alleviated IS-induced anxiety and high-fat-diet-induced gut inflammation in mice [ 22 , 23 ].…”

“…Bifidobacterium adolescentis IM38 alleviated IS-induced anxiety and high-fat-diet-induced gut inflammation in mice [ 22 , 23 ]. Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 mitigate stress-induced depression and colitis in mice by the attenuation of gut dysbiosis [ 16 , 20 ]. NVP1704, a combination of NK33 and NK98, alleviates depressive and anxious symptoms in individuals with anxiety, depression, and insomnia [ 24 ].…”

Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial

“…The probiotic NVP-1704 is a mixture of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 isolated from the healthy human gut microbiota [ 17 ], and several preclinical trials have showed that NVP-1704 can alleviate anxiety and depression in mice by modulating gut immune responses and gut microbiota composition [ 17 , 18 ]. Translational research to confirm these psychotropic effects of NVP-1704 may be the first step to providing a novel therapeutic approach to alleviate psychiatric symptoms.…”