• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.57-63
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• 1997

Animal and clinical investigations have shown that fluoroquinolones, new quinolone antibacterial agents (NQs), are well absorbed across the intestinal tract, with a bioavailability of 60-90% after oral administration. Although some types of carrier-mediated intestinal transport mechanisms have been reported for enoxacin (ENX), ofloxacin (OFLX) and sparfloxacin (SPFX), recent results using a human intestinal epithelial cell line, Caco-2, indicated a passive or nonsaturable transport of SPFX, one of the most hydrophobic NQs. The mechanism underlying the intestinal absorption of NQs is still largely unknown. The distribution of NQs into peripheral tissues including erythrocytes is very rapid and their tissue-to-plasma concentration ratios (Kp) are considerably larger than those of inulin (an extracellular fluid space marker), in spite of almost complete ionization of NQs at the physiological pH. Our findings suggest that OFLX and lomefloxacin (LFLX) are taken up by rat erythrocytes via a transport system common to that of a water-soluble vitamin, nicotinic acid.

• Food Science of Animal Resources
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• v.37 no.6
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• pp.931-939
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• 2017

Alcoholic liver disease (ALD) is a complex multifaceted disease that involves oxidative stress and inflammation as the key mediators. Despite decades of intensive research, there are no FDA-approved therapies, and/or no effective cure is yet available. Probiotics have received increasing attention in the past few years due to their well-documented gastrointestinal health-promoting effects. Interestingly, emerging studies have suggested that certain probiotics may offer benefits beyond the gut. Lactobacillus fermentum LA12 has been previously demonstrated to play a role in inflammatory-related disease. However, the possible protective effect of L. fermentum LA12 on ALD still remain to be explored. Thus, the aim of this study was to evaluate the possible protective effect of L. fermentum LA12 on alcohol-induced gut barrier dysfunction and liver damage in a rat model of alcoholic steatohepatitis (ASH). Daily oral administration of L. fermentum LA12 in rat model of ASH for four weeks was shown to significantly reduced intestinal nitric oxide production and hyperpermeability. Moreover, small intestinal histological- and qRT-PCR analysis further revealed that L. fermentum LA12 treatment was capable of up-regulating the mRNA expression levels of tight junction proteins, thereby stimulating the restitution of barrier structure and function. Serum and hepatic analyses also revealed that the restoration of epithelial barrier function may prevent the leakage of endotoxin into the blood, subsequently improve liver function and hepatic steatosis in the L. fermentum LA12-treated rats. Altogether, results in this study suggest that L. fermentum LA12 may be used as a dietary adjunct for the prevention and treatment of ASH.

• Journal of Microbiology and Biotechnology
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• v.25 no.4
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• pp.479-491
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• 2015

Lactobacillus species have been shown to enhance intestinal epithelial barrier function, modulate host immune responses, and suppress the growth of pathogenic bacteria, yeasts, molds, and viruses. Thus, lactobacilli have been used as probiotics for treating various diseases, including intestinal disorders, and as biological preservatives in the food and agricultural industries. However, the molecular mechanisms used by lactobacilli to suppress pathogenic bacterial infections have been poorly characterized. We previously isolated Lactobacillus plantarum JSA22 from buckwheat sokseongjang, a traditional Korean fermented soybean food, which possessed high enzymatic, fibrinolytic, and broad-spectrum antimicrobial activity against foodborne pathogens. In this study, we investigated the effects of L. plantarum JSA22 on the growth of S. Typhimurium and S. Typhimurium-induced cytotoxicity by stimulating the host immune response in intestinal epithelial cells. The results showed that coincubation of S. Typhimurium and L. plantarum JSA22 with intestinal epithelial cells suppressed S. Typhimurium infection, S. Typhimurium-induced NF-κB activation, and IL-8 production, and lowered the phosphorylation of both Akt and p38. These data indicated that L. plantarum JSA22 has probiotic properties, and can inhibit S. Typhimurium infection of intestinal epithelial cells. Our findings can be used to develop therapeutic and prophylactic agents against pathogenic bacteria.

• Journal of Radiation Protection and Research
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• v.45 no.4
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• pp.163-170
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• 2020

Background: Gut microflora contributes to the nutritional metabolism of the host and to strengthen its immune system. However, if the intestinal barrier function of the living body is destroyed by radiation exposure, the intestinal bacteria harm the health of the host and cause sepsis. Therefore, this study aims to trace short-term radiation-induced changes in the mouse gut microflora-dominant bacterial genus, and analyze the degree of intestinal epithelial damage. Materials and Methods: Mice were irradiated with 0, 2, 4, 8 Gy X-rays, and the gut microflora and intestinal epithelial changes were analyzed 72 hours later. Five representative genera of Actinobacteria, Firmicutes, and Bacteroidetes were analyzed in fecal samples, and the intestine was pathologically analyzed by Hematoxylin-Eosin and Alcian blue staining. In addition, DNA fragmentation was evaluated by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Results and Discussion: The small intestine showed shortened villi and reduced number of goblet cells upon 8 Gy irradiation. The large intestine epithelium showed no significant morphological changes, but the number of goblet cells were reduced in a radiation dose-dependent manner. Moreover, the small intestinal epithelium of 8 Gy-irradiated mice showed significant DNA damaged, whereas the large intestine epithelium was damaged in a dose-dependent manner. Overall, the large intestine epithelium showed less recovery potential upon radiation exposure than the small intestinal epithelium. Analysis of the intestinal flora revealed fluctuations in lactic acid bacteria excretion after irradiation regardless of the morphological changes of intestinal epithelium. Altogether, it became clear that radiation exposure could cause an immediate change of their excretion. Conclusion: This study revealed changes in the intestinal epithelium and intestinal microbiota that may pave the way for the identification of novel biomarkers of radiation-induced gastrointestinal disorders and develop new therapeutic strategies to treat patients with acute radiation syndrome.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.265-273
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• 2023

Background: The intestinal microbiota is an important regulator of bone health. In previous studies we have shown that intestinal microbiota dysbiosis, induced by treatment with broad spectrum antibiotics (ABX) followed by natural repopulation, results in gut barrier dysfunction and bone loss. We have also shown that treatment with probiotics or a gut barrier enhancer can inhibit dysbiosis-induced bone loss. The overall goal of this project was to test the effect of Korean Red Ginseng (KRG) extract on bone and gut health using antibiotics (ABX) dysbiosis-induced bone loss model in mice. Methods: Adult male mice (Balb/C, 12-week old) were administered broad spectrum antibiotics (ampicillin and neomycin) for 2 weeks followed by 4 weeks of natural repopulation. During this 4-week period, mice were treated with vehicle (water) or KRG extract. Other controls included mice that did not receive either antibiotics or KRG extract and mice that received only KRG extract. At the end of the experiments, we assessed various parameters to assess bone, microbiota and in vivo intestinal permeability. Results: Consistent with our previous results, post-ABX- dysbiosis led to significant bone loss. Importantly, this was associated with a decrease in gut microbiota alpha diversity and an increase in intestinal permeability. All these effects including bone loss were prevented by KRG extract treatment. Furthermore, our studies identified multiple genera including Lactobacillus and rc4-4 as well as Alistipes finegoldii to be potentially linked to the effect of KRG extract on gut-bone axis. Conclusion: Together, our results demonstrate that KRG extract regulates the gut-bone axis and is effective at preventing dysbiosis-induced bone loss in mice.

• Journal of Periodontal and Implant Science
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• v.48 no.5
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• pp.284-294
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• 2018

Purpose: Epithelial barrier dysfunction is involved in the pathophysiology of periodontitis and oral lichen planus. Estrogens have been shown to enhance the physical barrier function of intestinal and esophageal epithelia, and we aimed to investigate the effect of estradiol (E2) on the regulation of physical barrier and tight junction (TJ) proteins in human oral epithelial cell monolayers. Methods: HOK-16B cell monolayers cultured on transwells were treated with E2, an estrogen receptor (ER) antagonist (ICI 182,780), tumor necrosis factor alpha ($TNF{\alpha}$), or dexamethasone (Dexa), and the transepithelial electrical resistance (TER) was then measured. Cell proliferation was measured by the cell counting kit (CCK)-8 assay. The levels of TJ proteins and nuclear translocation of nuclear factor $(NF)-{\kappa}B$ were examined by confocal microscopy. Results: E2 treatment increased the TER and the levels of junctional adhesion molecule (JAM)-A and zonula occludens (ZO)-1 in a dose-dependent manner, without affecting cell proliferation during barrier formation. Treatment of the tight-junctioned cell monolayers with $TNF{\alpha}$ induced decreases in the TER and the levels of ZO-1 and nuclear translocation of $NF-{\kappa}B$. These $TNF{\alpha}-induced$ changes were inhibited by E2, and this effect was completely reversed by co-treatment with ICI 182,780. Furthermore, E2 and Dexa presented an additive effect on the epithelial barrier function. Conclusions: E2 reinforces the physical barrier of oral epithelial cells through the nuclear ER-dependent upregulation of TJ proteins. The protective effect of E2 on the $TNF{\alpha}-induced$ impairment of the epithelial barrier and its additive effect with Dexa suggest its potential use to treat oral inflammatory diseases involving epithelial barrier dysfunction.

• Animal Bioscience
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• v.35 no.11
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• pp.1711-1724
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• 2022

Objective: The present study was to evaluate the effects of different rapeseed meal substitution (RSM) and glutamine (Gln) supplementation on growth performance, intestine morphology, and intestinal mucosa barrier of broilers. Methods: Four hundred and twenty Qiandongnan Xiaoxiang Chicken at 1 day of age with similar weight were chosen and were randomly assigned into 7 groups, consisting of 10 replicates per group and 6 broilers per replicate. Three groups were provided with diets separately containing 0%, 10%, and 20% RSM, and the other four groups were fed with diets separately supplemented with 0.5% and 1% Gln based on the inclusion of 10% and 20% RSM. At 21 and 42 days of age, 10 broilers per group were chosen to collect plasma and intestinal samples for further analysis. Results: The results showed that 10% RSM decreased average daily feed intake (ADFI) and average daily weight gain (ADG) of broilers at 21 days of age (p<0.05). Furthermore, both ADFI and ADG of broilers at 21 and 42 days of age were decreased by 20% RSM, while feed conversion ratio (FCR) was increased (p<0.05). Besides, 10% RSM resulted in lower intestinal villus height and the ratio of villus height to crypt depth, deeper crypt depth (p<0.05), combined with the lower mRNA expressions of occludin, claudin-1, and zonula occludens-1 (ZO-1) in broilers at 21 days of age (p<0.05). Similar results were also observed in broilers at 21 and 42 days of age fed with 20% RSM. However, 1% Gln improved the growth performance of broilers fed with 10% and 20% RSM (p<0.05), ameliorated intestine morphology and elevated mRNA expressions of occludin, claudin-1 and ZO-1 (p<0.05). Conclusion: In conclusion, the increasing inclusion of RSM resulted in more serious effects on broilers, however, 1.0% Gln could reverse the negative effects induced by the inclusion of RSM.

• Nutrition Research and Practice
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• v.17 no.4
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• pp.616-630
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• 2023

BACKGROUND/OBJECTIVES: Indole-3-propionic acid (IPA) is a tryptophan-derived microbial metabolite that has been associated with protective effects against inflammatory and metabolic diseases. However, there is a lack of knowledge regarding the effects of IPA under physiological conditions and at the intestinal level. MATERIALS/METHODS: Human intestinal epithelial Caco-2 cells were treated for 2, 24, and/or 72 h with IPA or its precursors - indole, tryptophan, and propionate - at 1, 10, 100, 250, or 500 μM to assess cell viability, integrity, differentiation, and proliferation. RESULTS: IPA induced cell proliferation and this effect was associated with a higher expression of extracellular signal-regulated kinase 2 (ERK2) and a lower expression of c-Jun. Although indole and propionate also induced cell proliferation, this involved ERK2 and c-Jun independent mechanisms. On the other hand, both tryptophan and propionate increased cell integrity and reduced the expression of claudin-1, whereas propionate decreased cell differentiation. CONCLUSIONS: In conclusion, these findings suggested that IPA and its precursors distinctly contribute to the proliferation, differentiation, and barrier function properties of human intestinal epithelial cells. Moreover, the pro-proliferative effect of IPA in intestinal epithelial cells was not explained by its precursors and is rather related to its whole chemical structure. Maintaining IPA at physiological levels, e.g., through IPA-producing commensal bacteria, may be important to preserve the integrity of the intestinal barrier and play an integral role in maintaining metabolic homeostasis.

• IMMUNE NETWORK
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• v.21 no.3
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• pp.20.1-20.18
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• 2021

The gut is an important organ with digestive and immune regulatory function which consistently harbors microbiome ecosystem. The gut microbiome cooperates with the host to regulate the development and function of the immune, metabolic, and nervous systems. It can influence disease processes in the gut as well as extra-intestinal organs, including the brain. The gut closely connects with the central nervous system through dynamic bidirectional communication along the gut-brain axis. The connection between gut environment and brain may affect host mood and behaviors. Disruptions in microbial communities have been implicated in several neurological disorders. A link between the gut microbiota and the brain has long been described, but recent studies have started to reveal the underlying mechanism of the impact of the gut microbiota and gut barrier integrity on the brain and behavior. Here, we summarized the gut barrier environment and the 4 main gut-brain axis pathways. We focused on the important function of gut barrier on neurological diseases such as stress responses and ischemic stroke. Finally, we described the impact of representative environmental sensors generated by gut bacteria on acute neurological disease via the gut-brain axis.