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

2021 ◽  
pp. 1-12
Author(s):  
S.-W. Yun ◽  
J.-K. Kim ◽  
M.J. Han ◽  
D.-H. Kim
Keyword(s):  
Escherichia Coli ◽  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Psychiatric Disorders ◽  
Myeloperoxidase Activity ◽  
Bdnf Expression ◽  
Strain Collection ◽  
Tnf Α ◽  
Faecal Bacteria ◽  
Anxiety Depression

The gut microbiota communicates with the brain through microbiota-gut-brain (MGB) and hypothalamus-pituitary-adrenal (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 expression-suppressing 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-1β, IL-6, and tumour necrosis factor (TNF)-α expression, and nuclear factor kappa beta (NF-κB) 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-α expression, and NF-κB 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-α, and BDNF expression through the regulation of gut microbiota and NF-κB activation.

scholarly journals Buspirone alleviates anxiety, depression, and colitis; and modulates gut microbiota in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeon-Kyung Kim ◽  
Sang-Kap Han ◽  
Min-Kyung Joo ◽  
Dong-Hyun Kim
Keyword(s):  
Gut Microbiota ◽  
Normal Control ◽  
Cell Population ◽  
Intraperitoneal Administration ◽  
Fecal Microbiota ◽  
Myeloperoxidase Activity ◽  
Brain Functions ◽  
Β Diversity ◽  
Tnf Α ◽  
Anxiety Depression

AbstractGut microbiota regulate the neurodevelopmental processes and brain functions through the regulation of the microbiota–gut interaction and gut–brain communication. Buspirone, an agonist for serotonin 5-HT1A receptors, is used for the treatment of anxiety/depression. Therefore, to understand the gut microbiota-mediated mechanism of buspirone on anxiety/depression, we examined its effect on the immobilization stress (IS) or Escherichia coli K1 (EC)-induced anxiety/depression in mice. Oral or intraperitoneal administration of buspirone significantly suppressed stressor-induced anxiety/depression-like behaviors in the elevated plus maze, light/dark transition, tail suspension, and forced swimming tasks. Their treatments also reduced TNF-α expression and NF-κB+/Iba1+ cell population in the hippocampus and myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon. Buspirone treatments partially restored IS- or EC-induced gut microbiota perturbation such as β-diversity to those of normal control mice: they reduced the IS- or EC-induced gut Proteobacteria population. In particular, the anxiolytic activity of buspirone was positively correlated with the populations of Bacteroides and PAC001066_g in EC- or IS-exposed mice, while the populations of Lachnospiraceae, KE159660_g, LLKB_g, Helicobacter, and PAC001228_g were negatively correlated. The anti-depressant effect of buspirone was positively correlated with the Roseburia population. The fecal microbiota transplantations from buspirone-treated mice with IS-induced anxiety/depression or normal control mice suppressed IS-induced anxiety/depression-like behaviors and reduced hippocampal NF-κB+/Iba1+ and colonic NF-κB+/CD11c+ cell populations in the transplanted mice. Furthermore, they modified IS-induced perturbation of gut microbiota composition, particularly Proteobacteria, in the transplanted mice. In conclusion, buspirone alleviates IS as well as EC-induced anxiety/depression and colitis. It also suppresses associated neuroinflammation and modulates gut microbiota. Future studies can help to explain the relationship, if any, in the central and peripheral effects of buspirone.

scholarly journals A Probiotic Lactobacillus gasseri Alleviates Escherichia coli-Induced Cognitive Impairment and Depression in Mice by Regulating IL-1β Expression and Gut Microbiota

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3441
Author(s):  
Soo-Won Yun ◽  
Jeon-Kyung Kim ◽  
Kyung-Eon Lee ◽  
Young Joon Oh ◽  
Hak-Jong Choi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Neuropsychiatric Disorders ◽  
Activated Macrophages ◽  
Oral Gavage ◽  
Lactobacillus Gasseri ◽  
Specific Pathogen ◽  
The Brain ◽  
Escherichia Coli K1

Excessive expression of interleukin (IL)-1β in the brain causes depression and cognitive dysfunction. Herein, we investigated the effect of Lactobacillus gasseri NK109, which suppressed IL-1β expression in activated macrophages, on Escherichia coli K1-induced cognitive impairment and depression in mice. Germ-free and specific pathogen-free mice with neuropsychiatric disorders were prepared by oral gavage of K1. NK109 alleviated K1-induced cognition-impaired and depressive behaviors, decreased the expression of IL-1β and populations of NF-κB+/Iba1+ and IL-1R+ cells, and increased the K1-suppressed population of BDNF+/NeuN+ cells in the hippocampus. However, its effects were partially attenuated by celiac vagotomy. NK109 treatment mitigated K1-induced colitis and gut dysbiosis. Tyndallized NK109, even if lysed, alleviated cognitive impairment and depression. In conclusion, NK109 alleviated neuropsychiatric disorders and colitis by modulating IL-1β expression, gut microbiota, and vagus nerve-mediated gut–brain signaling.

scholarly journals Alleviation of cognitive impairment by gut microbiota lipopolysaccharide production-suppressing Lactobacillus plantarum and Bifidobacterium longum in mice

2021 ◽  
Author(s):  
Dong-Yun Lee ◽  
Yoon-Jung Shin ◽  
Jeon-Kyung Kim ◽  
Hyo-Min Jang ◽  
Min-Kyung Joo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Lactobacillus Plantarum ◽  
Bifidobacterium Longum ◽  
Bdnf Expression

Lactobacillus plantarum NK151 and Bifidobacterium longum NK173 alleviate stressor-induced cognitive impairment in colitis by upregulating NF-KB-mediated BDNF expression through the suppression of fecal and blood bacterial LPS levels.

scholarly journals Bifidobacteria-Fermented Red Ginseng and Its Constituents Ginsenoside Rd and Protopanaxatriol Alleviate Anxiety/Depression in Mice by the Amelioration of Gut Dysbiosis

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 901 ◽  
Author(s):  
Sang-Kap Han ◽  
Min-Kyung Joo ◽  
Jeon-Kyung Kim ◽  
Woonhee Jeung ◽  
Heerim Kang ◽  
...  
Keyword(s):  
Cell Population ◽  
Myeloperoxidase Activity ◽  
Red Ginseng ◽  
Trinitrobenzenesulfonic Acid ◽  
Bdnf Expression ◽  
Ginsenoside Rd ◽  
Gut Dysbiosis ◽  
Plus Maze ◽  
Anxiety Depression ◽  
The Brain

Gut dysbiosis is closely connected with the outbreak of psychiatric disorders with colitis. Bifidobacteria-fermented red ginseng (fRG) increases the absorption of ginsenoside Rd and protopanxatriol into the blood in volunteers and mice. fRG and Rd alleviates 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice. Therefore, to understand the gut microbiota-mediated mechanism of fRG against anxiety/depression, we examined the effects of red ginseng (RG), fRG, ginsenoside Rd, and protopanaxatriol on the occurrence of anxiety/depression, colitis, and gut dysbiosis in mice. Mice with anxiety/depression were prepared by being exposed to two stressors, immobilization stress (IS) or Escherichia coli (EC). Treatment with RG and fRG significantly mitigated the stress-induced anxiety/depression-like behaviors in elevated plus maze, light-dark transition, forced swimming (FST), and tail suspension tasks (TST) and reduced corticosterone levels in the blood. Their treatments also suppressed the stress-induced NF-κB activation and NF-κB+/Iba1+ cell population in the hippocampus, while the brain-derived neurotrophic factor (BDNF) expression and BDNF+/NeuN+ cell population were increased. Furthermore, treatment with RG or fRG suppressed the stress-induced colitis: they suppressed myeloperoxidase activity, NF-κB activation, and NF-κB+/CD11c+ cell population in the colon. In particular, fRG suppressed the EC-induced depression-like behaviors in FST and TST and colitis more strongly than RG. fRG treatment also significantly alleviated the EC-induced NF-κB+/Iba1+ cell population and EC-suppressed BDNF+/NeuN+ cell population in the hippocampus more strongly than RG. RG and fRG alleviated EC-induced gut dysbiosis: they increased Bacteroidetes population and decreased Proteobacteria population. Rd and protopanaxatriol also alleviated EC-induced anxiety/depression and colitis. In conclusion, fRG and its constituents Rd and protopanaxatriol mitigated anxiety/depression and colitis by regulating NF-κB-mediated BDNF expression and gut dysbiosis.

scholarly journals The Preventive and Curative Effects of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 on Immobilization Stress-Induced Anxiety/Depression and Colitis in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 819 ◽  
Author(s):  
Hyo-Min Jang ◽  
Kyung-Eon Lee ◽  
Dong-Hyun Kim
Keyword(s):  
Immune Responses ◽  
Immobilization Stress ◽  
Lactobacillus Reuteri ◽  
Myeloperoxidase Activity ◽  
Bdnf Expression ◽  
Healthy Human ◽  
Bifidobacterium Adolescentis ◽  
Development Of Anxiety ◽  
Anxiety Depression

The gut dysbiosis by stressors such as immobilization deteriorates psychiatric disorders through microbiota-gut-brain axis activation. To understand whether probiotics could simultaneously alleviate anxiety/depression and colitis, we examined their effects on immobilization stress (IS)-induced anxiety/depression and colitis in mice. The probiotics Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 were isolated from healthy human feces. Mice with anxiety/depression and colitis were prepared by IS treatment. NK33 and NK98 potently suppressed NF-κB activation in lipopolysaccharide (LPS)-induced BV-2 cells. Treatment with NK33 and/or NK98, which were orally gavaged in mice before or after IS treatment, significantly suppressed the occurrence and development of anxiety/depression, infiltration of Iba1+ and LPS+/CD11b+ cells (activated microglia) into the hippocampus, and corticosterone, IL-6, and LPS levels in the blood. Furthermore, they induced hippocampal BDNF expression while NF-κB activation was suppressed. NK33 and/or NK98 treatments suppressed IS-induced colon shortening, myeloperoxidase activity, infiltration of CD11b+/CD11c+ cells, and IL-6 expression in the colon. Their treatments also suppressed the IS-induced fecal Proteobacteria population and excessive LPS production. They also induced BDNF expression in LPS-induced SH-SY5Y cells in vitro. In conclusion, NK33 and NK98 synergistically alleviated the occurrence and development of anxiety/depression and colitis through the regulation of gut immune responses and microbiota composition.

scholarly journals Chaihu-Shugan-San (Shihosogansan) alleviates restraint stress-generated anxiety and depression in mice by regulating NF-κB-mediated BDNF expression through the modulation of gut microbiota

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sang-Kap Han ◽  
Jeon-Kyung Kim ◽  
Hee-Seo Park ◽  
Yeun-Jeong Shin ◽  
Dong-Hyun Kim
Keyword(s):  
Gut Microbiota ◽  
Restraint Stress ◽  
Corticosterone Level ◽  
Anxiety And Depression ◽  
Enzyme Linked Immunosorbent Assay ◽  
Myeloperoxidase Activity ◽  
Bdnf Expression ◽  
Fecal Transplantation ◽  
Gut Dysbiosis ◽  
Freeze Dried

Abstract Background Chaihu-Shugan-San (CSS, named Shihosogansan in Korean), a Chinese traditional medicine, is frequently used to treat anxiety and depression. Psychiatric disorders including depression are associated with gut dysbiosis. Therefore, to comprehend gut microbiota-involved anti-depressive effect of CSS, we examined its effect on restraint stress (RS)-induced depression and gut dysbiosis in mice Methods CSS was extracted with water in boiling water bath and freeze-dried. Anxiety and depression was induced in C57BL/6 mice by exposure to RS. Anxiety- and depression-like behaviors were measured in the light/dark transition and elevated plus maze tasks, forced swimming test, and tail suspension test. Biomarkers were assayed by using the enzyme-linked immunosorbent assay and immunoblotting. The gut microbiota composition was analyzed by Illumina iSeq sequencer. Results CSS significantly reduced the RS-induced anxiety- and depression-like behaviors in mice. CSS suppressed the RS-induced activation of NF-κB and expression of interleukin (IL)-6 and increased the RS-suppressed expression of brain-derived neurotrophic factor (BDNF). Furthermore, CSS suppressed the RS-induced IL-6 and corticosterone level in the blood and IL-6 expression and myeloperoxidase activity in the colon. CSS decreased the RS-induced γ-Proteobacteria population in gut microbiota, while the RS-suppressed Lactobacillaceae, Prevotellaceae, and AC160630_f populations increased. Fecal transplantation of vehicle-treated control or RS/CSS-treated mice into RS-exposed mice significantly mitigated RS-induced anxity- and depression-like behaviors, suppressed the NF-κB activation in the hippocampus and colon, and reduced the IL-6 and corticosterone levels in the blood. These fecal microbiota transplantations suppressed RS-induced Desulfovibrionaceae and γ-Proteobacteria populations and increased RS-suppressed Lactobacillaceae and Prevotellaceae poulation in the gut microbiota. Conclusions CSS alleviated anxiety and depression by inducing NF-κB-involved BDNF expression through the regulation of gut inflammation and microbiota.

scholarly journals Lactobacillus rhamnosus HDB1258 modulates gut microbiota-mediated immune response in mice with or without lipopolysaccharide-induced systemic inflammation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sang-Kap Han ◽  
Yeon-Jeong Shin ◽  
Dong-Yeon Lee ◽  
Kyung Min Kim ◽  
Seo-Jin Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Gut Microbiota ◽  
Oral Administration ◽  
Systemic Inflammation ◽  
Nk Cell ◽  
Lactobacillus Rhamnosus ◽  
Expression Ratio ◽  
Macrophage Phagocytosis ◽  
Tnf Α ◽  
Gut Microbiota Composition

Abstract Background Gut microbiota closely communicate in the immune system to maintain a balanced immune homeostasis in the gastrointestinal tract of the host. Oral administration of probiotics modulates gut microbiota composition. In the present study, we isolated Lactobacillus rhamnosus HDB1258, which induced tumor necrosis factor (TNF)-α and interleukin (IL)-10 expression in macrophages, from the feces of breastfeeding infants and examined how HDB1258 could regulate the homeostatic immune response in mice with or without lipopolysaccharide (LPS)-induced systemic inflammation. Results Oral administration of HDB1258 significantly increased splenic NK cell cytotoxicity, peritoneal macrophage phagocytosis, splenic and colonic TNF-α expression, TNF-α to IL-10 expression ratio, and fecal IgA level in control mice, while Th1 and Treg cell differentiation was not affected in the spleen. However, HDB1258 treatment significantly suppressed peritoneal macrophage phagocytosis and blood prostaglandin E2 level in mice with LPS-induced systemic inflammation. Its treatment increased LPS-suppressed ratios of Treg to Th1 cell population, Foxp3 to T-bet expression, and IL-10 to TNF-α expression. Oral administration of HDB1258 significantly decreased LPS-induced colon shortening, myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon, while the ratio of IL-10 to TNF-α expression increased. Moreover, HDB1258 treatment shifted gut microbiota composition in mice with and without LPS-induced systemic inflammation: it increased the Cyanobacteria and PAC000664_g (belonging to Bacteroidetes) populations and reduced Deferribacteres and EU622763_s group (belonging to Bacteroidetes) populations. In particular, PAC001066_g and PAC001072_s populations were negatively correlated with the ratio of IL-10 to TNF-α expression in the colon, while the PAC001070_s group population was positively correlated. Conclusions Oral administered HDB1258 may enhance the immune response by activating innate immunity including to macrophage phagocytosis and NK cell cytotoxicity in the healthy host and suppress systemic inflammation in the host with inflammation by the modulation of gut microbiota and IL-10 to TNF-α expression ratio in immune cells.

scholarly journals Effects of Pueraria candollei var mirifica (Airy Shaw and Suvat.) Niyomdham on Ovariectomy-Induced Cognitive Impairment and Oxidative Stress in the Mouse Brain

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3442
Author(s):  
Yaowared Chulikhit ◽  
Wichitsak Sukhano ◽  
Supawadee Daodee ◽  
Waraporn Putalun ◽  
Rakvajee Wongpradit ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Morris Water Maze Test ◽  
Object Recognition Test ◽  
Pueraria Mirifica ◽  
Beneficial Effects ◽  
Maze Test ◽  
Y Maze ◽  
Tnf Α ◽  
17Β Estradiol

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17β-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17β-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1β, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.

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