Lactobacillus gasseri NK109 and Its Supplement Alleviate Cognitive Impairment in Mice by Modulating NF-κB Activation, BDNF Expression, and Gut Microbiota Composition.

Aging-related gut microbiota dysbiosis initiates gut inflammation and microbiota dysbiosis, which induce the occurrence of psychiatric disorders including dementia. The alleviation of gut microbiota dysbiosis by probiotics is suggested to be able to alleviate psychiatric disorders including cognitive impairment (CI). Therefore, to understand how probiotics could alleviate CI, we examined the effects of anti-inflammatory Lactobacillus gasseri NK109 and its supplement (NS, mixture of NK109 and soybean embryo ethanol extract) on cognitive function in aged (Ag), 5XFAD transgenic (Tg), or mildly cognition-impaired adult fecal microbiota (MCF)-transplanted mice. Oral administration of NK109 or NS decreased CI-like behaviors in Ag mice. Their treatments suppressed TNF-α and p16 expression and NF-κB-activated cell populations in the hippocampus and colon, while BDNF expression was induced. Moreover, they partially shifted the ß-diversity of gut microbiota in Ag mice to those of young mice: they decreased Bifidobacteriaceae, Lactobacillaceae, and Helicobacteriaceae populations and increased Rikenellaceae and Prevotellaceae populations. Oral administration of NK109 or NS also reduced CI-like behaviors in Tg mice. Their treatments induced BDNF expression in the hippocampus, decreased hippocampal TNF-α and Aß expression and hippocampal and colonic NF-κB-activated cell populations. NK109 and NS partially shifted the ß-diversity of gut microbiota in Tg mice: they decreased Muribaculaceae and Rhodospiraceae populations and increased Helicobacteriaceae population. Oral administration of NK109 or NS decreased MCF transplantation-induced CI-like behaviors in mice. NK109 and NS increased hippocampal BDNF expression, while hippocampal and colonic TNF-α expression and NF-κB-activated cell populations decreased. These findings suggest that dementia can fluctuate the gut microbiota composition and NK109 and its supplement NS can alleviate CI with systemic inflammation by inducing BDNF expression and suppressing NF-κB activation and gut microbiota dysbiosis.

Rice yogurt with various beans fermented by lactic acid bacteria from kimchi.

In this study, the rice yogurt with various beans was developed using a mixture of rice saccharification solution as an artificial sweetener substitute and bean milk as a milk substitute. Rice yogurt was fermented with lactic acid bacteria isolated from kimchi. The lactic acid bacteria count in rice yogurt with various beans had the highest range of 9.37- 9.54 log CFU/g at 12 h fermentation. Also, at 12 h fermentation, pH ranged from 4.05 to 4.20. Rice yogurt with seoritae had the highest brix (15.52°Bx) and DPPH radical scavenging activity (41.86%). In the sensory evaluation, rice yogurt with seoritae received high preference scores in most categories, including flavor, sweet taste, sour taste, mouthfeel and overall preference. These findings suggest that the optimum fermentation time may be 12 h, and rice saccharification solution is an appropriate sugar substitute. Seoritae milk is suitable for the development of rice yogurt with beans.

DW2009 Elevates the Efficacy of Donepezil against Cognitive Impairment in Mice.

Lactobacillus plantarum C29 and DW2009 (C29-fermented soybean) alleviate cognitive impairment through the modulation of the microbiota-gut-brain axis. Therefore, we examined whether combining donepezil, a well-known acetylcholinesterase inhibitor, with C29 or DW2009 could synergistically alleviate cognitive impairment in mice. Oral administration of donepezil combined with or without C29 (DC) or DW2009 (DD) alleviated lipopolysaccharide (LPS)-induced cognitive impairment-like behaviors more strongly than treatment with each one alone. Their treatments significantly suppressed the NF-κB+/Iba1+ (activated microglia) population, NF-κB activation, and tumor necrosis factor-α and interleukin-1ß expression in the hippocampus, while the brain-derived neurotropic factor (BDNF)+/NeuN+ cell population and BDNF expression increased. Their treatments strongly suppressed LPS-induced colitis. Moreover, they increased the Firmicutes population and decreased the Cyanobacteria population in gut microbiota. Of these, DD most strongly alleviated cognitive impairment, followed by DC. In conclusion, DW2009 may synergistically or additively increase the effect of donepezil against cognitive impairment and colitis by regulating NF-κB-mediated BDNF expression.

Lactobacillus plantarum and Bifidobacterium bifidum alleviate dry eye in mice with exorbital lacrimal gland excision by modulating gut inflammation and microbiota.

In order to understand the efficacy of probiotics against dry eye syndrome, we selected anti-inflammatory probiotics Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175, which increased the ratio of IL-10 to TNF-α expression, from the human gut bacteria collection and examined their effects on tear secretion and cornea/conjunctiva inflammation in mice with excision of the unilateral exorbital lacrimal gland and 1% atropine and 0.1% benzalkonium chloride solution (ELA)-induced dry eye. Exposure to ELA significantly reduced tear secretion in mice, assessed by the phenol red thread tear test. However, oral gavage of NK151 and/or NK175 significantly increased ELA-suppressed tear secretion, IL-10 expression, and goblet cell population and decreased the ELA-induced corneal fluorescein-staining score, IL-1ß and TNF-α expression in the conjunctiva. They also suppressed ELA-induced myeloperoxidase, IL-1ß, and TNF-α expression. In particular, they increased the ratio of IL-10 to TNF-α expression in the colon. Their treatments increased ELA-induced α-diversity reduction to that of the control group and partially restored ELA-shifted ß-diversity to that of the control group. Oral gavage of NK151 and/or NK175 reduced ELA-induced Verrucomicrobia and Actinobacteria populations at the phylum level. Furthermore, they reduced ELA-induced Bacteroidaceae, Akkemansiaceae, and AC160630_f populations and increased ELA-suppressed Lactobacillaceae and Muribaculaceae populations at the family level. These gut bacteria populations exhibited significant correlation with the tear secretion volume. In conclusion, NK151 and/or NK175 alleviated dry eye by modulating the expression ratio of pro-inflammatory cytokines such as TNF-α and anti-inflammatory cytokines such as IL-10 and gut microbiota composition.

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

Excessive expression of interleukin (IL)-1ß in the brain causes depression and cognitive dysfunction. Herein, we investigated the effect of Lactobacillus gasseri NK109, which suppressed IL-1ß 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-1ß 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-1ß expression, gut microbiota, and vagus nerve-mediated gut-brain signaling.

Effects of Red and Fermented Ginseng and Ginsenosides on Allergic Disorders.

Both white ginseng (WG, dried root of Panax sp.) and red ginseng (RG, steamed and dried root of Panax sp.) are reported to exhibit a variety of pharmacological effects such as anticancer, antidiabetic, and neuroprotective activities. These ginsengs contain hydrophilic sugar-conjugated ginsenosides and polysaccharides as the bioactive constituents. When taken orally, their hydrophilic constituents are metabolized into hydrophobic ginsenosides compound K, Rh1, and Rh2 that are absorbable into the blood. These metabolites exhibit the pharmacological effects more strongly than hydrophilic parental constituents. To enforce these metabolites, fermented WG and RG are developed. Moreover, natural products including ginseng are frequently used for the treatment of allergic disorders. Therefore, this review introduces the current knowledge related to the effectiveness of ginseng on allergic disorders including asthma, allergic rhinitis, atopic dermatitis, and pruritus. We discuss how ginseng, its constituents, and its metabolites regulate allergy-related immune responses. We also describe how ginseng controls allergic disorders.

IL-10 Expression-Inducing Gut Bacteria Alleviate High-Fat Diet-Induced Obesity and Hyperlipidemia in Mice.

In the present study, we examined the effects of interleukin (IL)-10 expression-inducing bacteria Bifidobacterium adolescentis HP1, Lactobacillus mucosae HP2, and Weissella cibaria HP3 on high-fat diet (HFD)-induced obesity and liver steatosis in mice. Oral gavage of HP1, HP2, and HP3 reduced HFD-induced bodyweight gain, triglycerides, and total cholesterol levels in the blood and liver. They also suppressed HFD-induced colitis and the fecal δ,γ-Proteobacteria population. Of the tested bacteria, HP2, which most potently inhibited IL-10 expression, also suppressed HFD-induced bodyweight gain, liver steatosis, and colitis most effectively. These findings suggest that IL-10 expression-inducing gut bacteria can suppress obesity and liver steatosis.

Fermented red ginseng and ginsenoside Rd alleviate ovalbumin-induced allergic rhinitis in mice by suppressing IgE, interleukin-4, and interleukin-5 expression.

BACKGROUND: To increase the pharmacological effects of red ginseng (RG, the steamed root of Panax ginseng Meyer), RG products modified by heat process or fermentation have been developed. However, the antiallergic effects of RG and modified/fermented RG have not been simultaneously examined. Therefore, we examined the allergic rhinitis (AR)-inhibitory effects of water-extracted RG (wRG), 50% ethanol-extracted RG (eRG), and bifidobacteria-fermented eRG (fRG) in vivo. METHODS: RBL-2H3 cells were stimulated with phorbol 12-myristate-13-acetate/A23187. Mice with AR were prepared by treatment with ovalbumin. Allergic markers IgE, tumor necrosis factor-α, interleukin (IL)-4, and IL-5 were assayed in the blood, bronchoalveolar lavage fluid, nasal mucosa, and colon using enzyme-linked immunosorbent assay. Mast cells, eosinophils, and Th2 cell populations were assayed using a flow cytometer. RESULTS: RG products potently inhibited IL-4 expression in phorbol 12-myristate-13-acetate/A23187-stimulated RBL-2H3 cells. Of tested RG products, fRG most potently inhibited IL-4 expression. RG products also alleviated ovalbumin-induced AR in mice. Of these, fRG most potently reduced nasal allergy symptoms and blood IgE levels. fRG treatment also reduced IL-4 and IL-5 levels in bronchoalveolar lavage fluid, nasal mucosa, and reduced mast cells, eosinophils, and Th2 cell populations. Furthermore, treatment with fRG reduced IL-4, IL-5, and IL-13 levels in the colon and restored ovalbumin-suppressed Bacteroidetes and Actinobacteria populations and ovalbumin-induced Firmicutes population in gut microbiota. Treatment with ginsenoside Rd significantly alleviated ovalbumin-induced AR in mice. CONCLUSION: fRG and ginsenoside Rd may alleviate AR by suppressing IgE, IL-4, IL-5, and IL-13 expression and restoring the composition of gut microbiota.

Lactobacillus plantarum NK3 and Bifidobacterium longum NK49 Alleviate Bacterial Vaginosis and Osteoporosis in Mice by Suppressing NF-κB-Linked TNF-α Expression.

Excessive expression of TNF-α worsens bacterial vaginosis (BV) and osteoporosis. Therefore, to understand whether probiotics could alleviate vaginosis and osteoporosis, we isolated anti-inflammatory Lactobacillus plantarum NK3 and Bifidobacterium longum NK49 from kimchi and human fecal lactic acid bacteria collection and examined their effects on Gardnerella vaginalis (GV)-induced vaginosis and ovariectomy-induced osteoporosis in female mice. Oral gavage of NK3 and/or NK49 significantly alleviated GV-induced vaginosis; these inhibited NF-κB activation and TNF-α expression in the vagina and uterus, and decreased the GV population in the vagina. Furthermore, treatment with NK3 and/or NK49 alleviated ovariectomy-induced osteoporosis and obesity; these increased blood calcium, phosphorus, and osteocalcin levels and suppressed body weight. GV-induced vaginosis and ovariectomy increased colonic myeloperoxidase activity, TNF-α expression, and fecal Proteobacteria population. NK3 and/or NK49 treatments reduced TNF-α expression and NF-κB activation in the colon. NK3 and NK49 treatment also restored GV- or ovariectomy-disrupted gut microbiota composition. In conclusion, NK3 and NK49 may simultaneously alleviate BV and osteoporosis by suppressing NF-κB-linked TNF-α expression through the regulation of gut microbiota population.

The fermentation characteristics of soy yogurt with different content of d-allulose and sucrose fermented by lactic acid bacteria from Kimchi.

In this study, to understand whether d-allulose, an ultra-low calorie sweetener, was available in soy yogurt fermentation, we isolated Leuconostoc mesenteroides and Lactobacillus plantarum from kimchi and fermented in soymilk at various contents of d-allulose and sucrose. The lactic acid bacteria counts in soy yogurt had the highest range of 9.23-9.49 log CFU/g at 24 h fermentation and then decreased. At 48 h fermentation, the pH showed 4.31 and 4.52 in the samples containing 75% and 100% d-allulose as sweetener. DPPH radical scavenging activity showed a decreasing tendency as the amount of d-allulose increased. Soy yogurt samples containing d-allulose had higher scores in sweet taste, sour taste and overall preference in sensory evaluation. These findings suggest that d-allulose is beneficial for the development of a low calorie soy yogurt.

Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 simultaneously alleviate high-fat diet-induced colitis, endotoxemia, liver steatosis, and obesity in mice.

Long-term feeding of a high-fat diet (HFD) induces endotoxemia and gastrointestinal inflammation by disturbing gut microbiota composition and membrane permeability, resulting in the acceleration of obesity. Some probiotics exhibit anti-inflammatory effects in vitro and in vivo. Therefore, we hypothesized that anti-inflammatory probiotics could lead to the simultaneous attenuation of endotoxemia, liver steatosis, obesity, and colitis in mice with HFD-induced obesity. Herein, we examined whether Lactobacillus plantarum LC27 and/or Bifidobacterium longum LC, which significantly suppressed NF-κB activation in lipopolysaccharide- or fecal lysate-stimulated Caco-2 cells, could simultaneously alleviate liver steatosis and colitis in mice with HFD-induced obesity. Oral administration of LC27, LC67, or their (3:1) mixture (LM) reduced HFD-induced aspartate transaminase, alanine transaminase, triglyceride, total cholesterol, and lipopolysaccharide levels in the blood and liver. Their treatments also suppressed HFD-induced NF-κB activation and increased AMP-activated protein kinase (AMPK) activation and claudin-1 and occludin expression in the liver and colon. Moreover, LC27, LC67, or LM treatment reduced HFD-induced Firmicutes and Proteobacteria populations in gut microbiota and fecal lipopolysaccharide production. The hypothesis was supported by the findings that anti-inflammatory LC27 and/or LC67 simultaneously alleviated liver steatosis, obesity, and colitis by regulating NF-κB and AMPK activation through the inhibition of gut microbiota lipopolysaccharide production.

Blackcurrant (Ribes nigrum) Prevents Obesity-Induced Nonalcoholic Steatohepatitis in Mice.

OBJECTIVE: With increasing prevalence of nonalcoholic steatohepatitis (NASH), effective strategies to prevent NASH are needed. This study investigated whether the consumption of blackcurrant (Ribes nigrum) can prevent the development of obesity-induced NASH in vivo. METHODS: Male C57BL/6J mice were fed a low-fat control diet, a low-fat diet with 6% whole blackcurrant powder, an obesogenic high-fat/high-sucrose control diet (HF), or a high-fat/high-sucrose diet containing 6% whole blackcurrant powder (HF-B) for 24 weeks. RESULTS: HF significantly increased, whereas HF-B markedly decreased, liver weights and triglyceride. Furthermore, blackcurrant attenuated obesity-induced infiltration of macrophages in the liver, in particular, the M1 type, and also suppressed the hepatic expression of fibrogenic genes and fibrosis. Flow cytometric analysis showed that HF significantly increased the percentages of monocytes of total splenocytes, which was markedly attenuated by blackcurrant. HF-B decreased lipopolysaccharide-stimulated mRNA expression of interleukin 1ß and tumor necrosis factor α in splenocytes, compared with those from HF controls. Moreover, the levels of circulating and hepatic miR-122-5p and miR-192-5p, known markers for nonalcoholic fatty liver disease, were significantly increased by HF but decreased by HF-B. CONCLUSIONS: The study's findings indicate that blackcurrant consumption prevents obesity-induced steatosis, inflammation, and fibrosis in the liver.

Astaxanthin exerts anti-inflammatory and antioxidant effects in macrophages in NRF2-dependent and independent manners.

Although anti-inflammatory effects of astaxanthin (ASTX) have been suggested, the underlying mechanisms have not been fully understood. Particularly, the modulatory action of ASTX in the interplay between nuclear factor E2-related factor 2 (NRF2) and nuclear factor κB (NFκB) to exert its anti-inflammatory effect in macrophages is unknown. The effect of ASTX on mRNA and protein expression of pro-inflammatory and antioxidant genes and/or cellular reactive oxygen species (ROS) accumulation were determined in RAW 264.7 macrophages, bone marrow-derived macrophages (BMDM) from wild-type (WT) and Nrf2-deficient mice, and/or splenocytes and peritoneal macrophages of obese mice fed ASTX. The effect of ASTX on M1 and M2 macrophage polarization was evaluated in BMDM. ASTX significantly decreased LPS-induced mRNA expression of interleukin 6 (Il-6) and Il-1ß by inhibiting nuclear translocation of NFκB p65; and attenuated LPS-induced ROS with an increase in NRF2 nuclear translocation, concomitantly decreasing NADPH oxidase 2 expression in RAW 264.7 macrophages. In BMDM of WT and Nrf2-deficient mice, ASTX decreased basal and LPS-induced ROS accumulation. The induction of Il-6 mRNA by LPS was repressed by ASTX in both types of BMDM while Il-1ß mRNA was decreased only in WT BMDM. Furthermore, ASTX consumption lowered LPS sensitivity of splenocytes in obese mice. ASTX decreased M1 polarization of BMDM while increasing M2 polarization. ASTX exerts its anti-inflammatory effect by inhibiting nuclear translocation of NFκB p65 and by preventing ROS accumulation in NRF2-dependent and -independent mechanisms. Thus, ASTX is an agent with anti-inflammatory and antioxidant properties that may be used for the prevention of inflammatory conditions.

Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 mitigate alcoholic steatosis in mice by inhibiting LPS-mediated NF-κB activation through restoration of the disturbed gut microbiota.

Long-term exposure to ethanol simultaneously causes gastrointestinal inflammation, liver injury, and steatosis. In the present study, we investigated the effects of Bifidobacterium longum LC67, Lactobacillus plantarum LC27, and their mixture (LM) against ethanol-induced steatosis in mice. Exposure to ethanol caused liver damage: it increased ALT, AST, TG, TC, and lipopolysaccharide levels in the blood and induced NF-κB activation in the liver. Oral administration of LC27, LC67, or LM in mice reduced ethanol-induced ALT, AST, TG, and TC levels in the blood and liver. These also suppressed ethanol-induced NF-κB activation and α-smooth muscle actin expression in the liver and increased ethanol-suppressed AMPK activation. Treatment with LC27, LC67, or LM increased ethanol-suppressed alcohol dehydrogenase and acetaldehyde dehydrogenase activities in the liver, as well as tight junction protein expression in the liver and colon. Moreover, treatment with LC27, LC67, or LM restored the ethanol-disturbed gut microbiota composition, such as the increased population of Proteobacteria, and inhibited fecal and blood lipopolysaccharide levels. These inhibited NF-κB activation and increased tight junction protein expression in ethanol- or lipopolysaccharide-stimulated Caco-2 cells. These findings suggest that LC27, LC67, and LM can alleviate alcoholic steatosis by inhibiting LPS-mediated NF-κB activation through restoration of the disturbed gut microbiota.

Evidence for interplay among antibacterial-induced gut microbiota disturbance, neuro-inflammation, and anxiety in mice.

The aim of the present study was to determine whether there is the mechanistic connection between antibacterial-dependent gut microbiota disturbance and anxiety. First, exposure of mice to ampicillin caused anxiety and colitis and increased the population of Proteobacteria, particularly Klebsiella oxytoca, in gut microbiota and fecal and blood lipopolysaccharide levels, while decreasing lactobacilli population including Lactobacillus reuteri. Next, treatments with fecal microbiota of ampicillin-treated mouse (FAP), K. oxytoca, or lipopolysaccharide isolated from K. oxytoca (KL) induced anxiety and colitis in mice and increased blood corticosterone, IL-6, and lipopolysaccharide levels. Moreover, these treatments also increased the recruitment of microglia (Iba1+), monocytes (CD11b+/CD45+), and dendritic cells (CD11b+/CD11c+) to the hippocampus, as well as the population of apoptotic neuron cells (caspase-3+/NeuN+) in the brain. Furthermore, ampicillin, K. oxytoca, and KL induced NF-κB activation and IL-1ß and TNF-α expression in the colon and brain as well as increased gut membrane permeability. Finally, oral administration of L. reuteri alleviated ampicillin-induced anxiety and colitis. These results suggest that ampicillin exposure can cause anxiety through neuro-inflammation which can be induced by monocyte/macrophage-activated gastrointestinal inflammation and elevated Proteobacteria population including K. oxytoca, while treatment with lactobacilli suppresses it.

Simultaneous Amelioratation of Colitis and Liver Injury in Mice by Bifidobacterium longum LC67 and Lactobacillus plantarum LC27.

Disturbances in the gut microbiota composition are associated with chronic inflammatory diseases of the intestine and the liver. In a preliminary study, Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 could inhibit Escherichia coli growth and lipopolysaccharide-induced NF-κB activation linked to gut inflammation. Here, we investigated their effects on 2,4,6-trinitrobenzesulfonic acid (TNBS)-induced colitis and liver damage in mice. First, oral administration of LC27 or LC67 (1 × 109 CFU/mouse) inhibited TNBS-induced colon shortening [F(5,30) = 100.66, P < 0.05] and myeloperoxidase activity [F(5,30) = 56.48, P < 0.05]. These probiotics restored TNBS-induced disturbance of gut microbiota, leading to the suppression of Proteobacteria to Bacteroidetes ratio and fecal and blood lipopolysaccharide levels. Second, LC27 and LC67 inhibited TNBS-induced NF-κB activation, reversed TNBS-suppressed tight junction protein expression, and restored Th17/Treg balance. Also, treatment with LC27 or LC67 significantly decreased TNBS-induced alanine transaminase [ALT, F(5,30) = 3.50, P < 0.05] and aspartate transaminase [AST, F(5,30) = 12.81, P < 0.05] levels in the blood, as well as t-butylhydroperoxide-induced ALT and AST levels. Finally, the mixture of LC27 and LC67 (0.5 × 109 CFU/mouse, respectively) synergistically attenuated TNBS- or t-butylhydroperoxide-induced colitis and liver damage. The capability of LC27 and LC67 to reverse TNBS-mediated microbiota shift and damage signals suggests that these probiotics may synergistically attenuate colitis and liver injury by alleviating gut microbiota imbalance.

Lactobacillus plantarum C29 Alleviates TNBS-Induced Memory Impairment in Mice.

In a preliminary study, Lactobacillus plantarum C29 was found to suppress 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice. Therefore, to understand whether an anti-colitic probiotic C29 could attenuate memory impairment, we examined the effects of C29 on TNBS-induced memory impairment in mice. Orally administered Lactobacillus plantarum C29 attenuated TNBS-induced memory impairment in mice in the Y-maze, noble object, and passive avoidance task tests. C29 treatment increased TNBS-suppressed hippocampal brain-derived neurotrophic factor expression and inhibited TNBS-induced hippocampal NF-kappaB activation and blood LPS levels. Moreover, C29 restored the TNBS-disturbed gut microbiota composition. These findings suggest that C29 can alleviate memory impairment presumably by restoring the gut microbiota composition.

Correction: Jang, S.-E.; et al. Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus La-14 Attenuate Gardnerella vaginalis-Infected Bacterial Vaginosis in Mice. Nutrients 2017, 9, 531.

We would like to submit the following corrections to our recently published paper [1] due to the reported wrong name of probiotic mixture and the dose of some drugs. ...].

Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus La-14 Attenuate Gardnerella vaginalis-Infected Bacterial Vaginosis in Mice.

Oral administration of a probiotic mixture (PM; Respecta®) consisting of Lactobacillus rhamnosus HN001 (L1), Lactobacillus acidophilus La-14 (L2), and lactoferrin RCXTM results in colonization of these probiotics in the vagina of healthy women. Therefore, we examined whether vaginal colonization of the PM ingredients L1 and L2 could attenuate bacterial vaginosis (BV). BV was induced in mice via ß-estradiol-3-benzoate-induced immunosuppression and intravaginal inoculation with Gardnerella vaginalis (GV). Inflammatory markers were analyzed using enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, and flow cytometry. Oral or intravaginal administration of PM resulted in colonization of L1 and L2 in the vagina. Oral or intravaginal administration of L1, L2, or PM significantly inhibited GV-induced epithelial cell disruption, myeloperoxidase activity, NF-κB activation, and IL-1ß and TNF-α expression (p < 0.05). Administration of these probiotics also inhibited IL-17 and RORγt expression but increased IL-10 and Foxp3 expression. Of these probiotics, L2 most effectively attenuated GV-induced BV, followed by L1 and PM. Oral administration was more effective against GV-induced BV than intravaginal administration. L1 and L2 also significantly inhibited the adherence of GV to HeLa cells (a human cervical cancer cell line) and GV growth in vitro. In addition, L1 and L2 inhibited lipopolysaccharide-induced NF-κB activation in macrophages and the differentiation of splenocytes into Th17 cells in vitro, but increased their differentiation into Treg cells. Our study suggests that L1, L2, and PM attenuated GV-induced vaginosis by regulating both vaginal and systemic innate and adaptive immune responses rather than direct competition or killing of GV in the vagina.

Irisolidone attenuates ethanol-induced gastric injury in mice by inhibiting the infiltration of neutrophils.

SCOPE: This study was designed to determine whether irisolidone and its glycoside kakkalide, which are the major constituents of the flower of Pueraria lobata (Kudzu) can attenuate ethanol-induced gastritic injury in mice. METHODS AND RESULTS: Irisolidone and kakkalide inhibited IL-8 secretion and NF-κB activation in lipopolysaccharide-stimulated KATO III cells. Therefore, we investigated their protective effects against ethanol-induced gastric injury in mice. Pretreatment with kakkalide or irisolidone decreased the area of hemorrhagic ulcerative lesions caused by ethanol and suppressed stomach myeloperoxidase activity, CXCL4 secretion, and NF-κB activation. The ameliorating effect of irisolidone was more potent than that of kakkalide. CONCLUSION: Irisolidone may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, particularly neutrophils, through the regulation of CXCL-4 or IL-8 secretion.