Characteristics of Bone Marrow Derived Mesenchymal Stem Cells in Patients with Liver Cirrhosis

( Haripriya Gupta ),( Sang Jun Yoon ),( Dae Hee Han ),( Na Young Lee ),( Ki Tae Suk ),( Dong Joon Kim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Cirrhosis is the end stage of chronic liver disease, which may lead to severe hepatic dysfunction and even life-threatening conditions. The beneficial impact of mesenchymal stem cells (MSCs) transplantation on liver diseases has been confirmed on several studies include our previous clinical trial for autologous bone marrow-derived mesenchymal stem cells (BM MSCs) transplantation to patients with liver cirrhosis, which have shown the ability of MSCs to reduce liver cirrhosis and improve liver function. We aimed to identify secreted factors by undifferentiated BM-MSCs in order to describe related pathways potentially targeted gene by MSC in liver cirrhosis. Methods: Human BM-MSCs from normal and patients who had liver cirrhosis after autologous BM-MSCs transplanted and cultured specific medium condition for mesenchymal stem cells. We evaluated the potential of differentiation to osteoblast and adipocytes, morphological changes and cell proliferation depending on culture period, and immunophenotyping assay with flow cytometer with CD14, CD34, CD45, CD73 and CD105. At passage 4-5 of BM-MSCs were used for cDNA microarrays to identify secreted genes and related pathway that differentially expressed in specific stem cell population in liver cirrhosis and identified by biomathmatical analysis. Results: On immunophenotyping analysis to determine mesenchymal function, CD14, CD34 and CD45 were 0.88%, 0.68% and 0.78%, respectively, however CD73 and CD105 for specific antigen of MSCs were 99.81% and 99.92%. BM MSCs secreted different factors in normal and patients with liver cirrhosis. We found 2968 genomes of 15 maps in KEGG pathway include Metabolic pathways, TGF-beta signaling pathway, Wnt signaling pathway, Cytokine-cytokine receptor interaction, HIF- 1 signaling pathway, Ras signaling pathway and Natural killer cell mediated cytotoxicity. Within these pathways, functionally up-regulated genes were 7 genes and down-regulated genes were 9. In particular, we were able to identify potential specific genes might have typical function for regulation of liver cirrhosis and regeneration (FBN2, P4HA1 and STC1), and KIR3DL2, which is gene for regulation of immune system process. Conclusions: Based on our previous clinical trial for autologous BM MSCs transplantation to patients with liver cirrhosis, the results have shown the ability of MSCs to reduce liver cirrhosis and improve liver function. Application of MSCs might target a widespread pattern of biological, cellular compositional and molecular functional event in the liver. MSC secreted genes and proteins can be differ depending on pathways and molecular mechanisms. Genes involved liver cirrhosis are able to release hepatotropic factors from transplanted MSCs, also potentially supporting liver regenerations.

Gut Microbiome and Metabolomic Signatures in Alco-holic Liver Disease

( Raja Ganesan ),( Haripriya Gupta ),( Ye Rin Choi ),( Hyeong Seop Kim ),( Sang Jun Yoon ),( Yoseph Asmelash Gebru ),( Satya Priya Sharma ),( Dong Joon Kim ),( Ki Tae Suk ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Compositional Shift of Gut Microbiome According to the Complications In Patients With Liver Cirrhosis

( Satya Priya Sharma ),( Raja Ganesan ),( Haripriya Gupta ),( Ye Rin Choi ),( Hyeong Seop Kim ),( Sang Jun Yoon ),( Yoseph Asmelash Gebru ),( Dong Joon Kim ),( Ki Tae Suk ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Bifidobacterium Breve and Bifidobacterium longum Attenuate Western Diet Induced Nonalcoholic Fatty Liver Disease in Mice

( Sang Jun Yoon ),( Yoseph Asmelash ),( Raja Ganesan ),( Haripriya Gupta ),( Sung Min Won ),( Eun Ju Park ),( Satyapriya Sharma ),( Hyeong Seop Kim ),( Ye Rin Choi ),( Byeong Hyun Min ),( Min Kyo Jeon 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Effects of Probiotics for the Treatment of Non-Alcoholic Fatty Liver Disease in Mice Model

( Dae Hee Han ),( Sang Jun Yoon ),( Haripriya Gupta ),( Na Young Lee ),( Ki Tae Suk ),( Dong Joon Kim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, comprises a spectrum of diseases ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis, and cirrhosis. Currently, there are no Food and Drug Administration-approved therapies for NAFLD. The aim of this study is to find beneficial probiotics and assess the improvement in NAFLD animal model. Methods: Six-week male C57BL/6J mice were used in this study. Mice were randomly assigned to normal diet, Western-diet, and 9 Western diet+probiotics groups (n=10/group). Used probiotics strains are Lactobacillus acidophilus, L. plantarum, L. casei, L. paracasei, L. fermentum, L. helveticus, L. bulgaricus, Bifidobacterium bifidum, Pediococcus pentosaceus KID7). Each probiotics were administered to mice in the drinking water at concentration of 1 Х 10⁹ colony forming units(CFU)/g/day for 8 weeks. Liver/body weight ratio, liver enzyme (ALT, AST), cholesterol, and histologic findings (hepatitis and steatosis score)) were analyzed. Results: In the analysis of liver/body weight ratio, L. acidophilus (5.5±0.4, P<0.001), L. bulgaricus (5.1±0.5, P<0.001), P. pentosaceus KID7 (5.5±0.5, P=0.009), L. paracasei (5.7±0.4, P=0.032), and L. helveticus (5.2±0.4, P<0.001) groups showed significant improvement compared with that of Western group (6.2±0.6). All strains except B. bifidum were effective in improvement of liver enzyme (AST or ALT, P<0.05). All strains except B. bifidum and L. casei significantly reduced the level of cholesterol (P<0.05). In comparison of histology (hepatitis score/steatosis score), L. helveticus (1.3±0.5/1.7±0.7, P<0.001), L. fermentum (1.8±0.4/2.7±0.5, P=0.042), L. paracasei (1.6±0.5/2.1±0.9, P=0.035), P. pentosaceus KID7 (1.3±0.5/1.4±0.5, P<0.001), B. bifidum (1.6±0.5/2.5±0.8, P=0.037), L. bulgaricus (0.7±0.7/0.7±0.7, P<0.001), L. casei (1.8±0.4/2.1±0.6, P<0.001), L. plantarum (1.8±0.6/2.3±0.7, P=0.003), and L. acidophilus (1.6±0.7/1.8±0.6, P<0.001) groups reveled significant improvement compared with that of Western group (3.1±0.3/2.0±0.0). Conclusion: Our selected probiotics have beneficial effects on weight reduction, dyslipidemia, and liver inflammation and steatosis. Therefore, probiotics might be effective in the treatment of NALD by regulating the gut-liver axis.

Impact of Probiotics in NAFLD in Mice with Western Diet

( Sang Jun Yoon ),( Dae Hee Han ),( Haripriya Gupta ),( Na Young Lee ),( Ki Tae Suk ),( Dong Joon Kim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide. However, definitive medical treatment has not been established with the exception of lifestyle modification. Probiotics can be used as a promising mediation targeting gut-liver axis in NAFLD. The aim of study was to evaluate the impact of some strains in Western diet induced NAFLD mice model. Methods: We used 6-week aged C57BL/6 mouse and mice were divided into 8 groups (n=10/group; normal diet group, Western diet for 8 weeks group, and 6 Western diet with probiotics administration groups [10⁹ CFU/g, for 8 weeks]). Used probiotics strains are Lactobacillus reuteri, L. salivarius, L. gasseri, Bifidobacterium lactis, B. breve, and B. longum. We compared liver/body weight ratio, histology (fatty liver and hepatitis), liver enzymes (AST, ALT, and bilirubin), and cholesterol. Results: In the analysis of liver/body weight ratio, L. salivarius (5.73±0.52, P=0.028), B. breve (5.27±0.47, P=0.001), and B. longum (4.85±0.57, P<0.001) groups showed significant improvement compared with that of Western group (6.33±0.63). In comparison of histology (fatty liver score/ hepatitis score), L. salivarius (1.9±0.3/1.0±0.0, P<0.001), B. breve (1.2±0.7/0.9±0.6, P<0.001), L. gasseri (1.9±0.3/1.0±0.3, P<0.001), B. lactis (2.1±0.3/1.2±0.4, P<0.001), and B. longum (1.2±0.4/0.8±0.4, P<0.001) groups reveled significant improvement compared with that of Western group (3.0±0.4/1.9±0.3). Especially, B. breve and B. longum showed liver histology like that of normal control. All strains are effective in improvement of liver enzyme (ASTT or ALT, P<0.05). In case of B. longum, mean cholesterol level was significantly decreased after administration of B. longum (0.9±0.5/0.3±0.2, P<0.001) Conclusions: Gut-liver axis plays an important role in the NAFLD and probiotics effectively reduce inflammation and steatosis of the liver in NAFLD. In addition, B. longum can be used in the treatment of dyslipidemia.

Gut Lactobacillus and Probiotics Lactobacillus lactis/rhamnosis Ameliorate Liver Fibrosis in Prevention and Treatment

Won Sung Min,Lee Na Young,Oh Ki-Kwang,Gupta Haripriya,Sharma Satya Priya,Kim Kyung Hwan,Kim Byoung Kook,Joung Hyun Chae,Jeong Jin Ju,Ganesan Raja,Han Sang Hak,Yoon Sang Jun,Kim Dong Joon,Suk Ki Tae 한국미생물학회 2023 The journal of microbiology Vol.61 No.2

The progression and exacerbation of liver fibrosis are closely related to the gut microbiome. It is hypothesized that some probiotics may slow the progression of liver fibrosis. In human stool analysis [healthy group (n = 44) and cirrhosis group (n = 18)], difference in Lactobacillus genus between healthy group and cirrhosis group was observed. Based on human data, preventive and therapeutic effect of probiotics Lactobacillus lactis and L. rhamnosus was evaluated by using four mice fibrosis models. L. lactis and L. rhamnosus were supplied to 3,5-diethoxycarbonyl-1,4-dihydrocollidine or carbon tetrachloride-induced liver fibrosis C57BL/6 mouse model. Serum biochemical measurements, tissue staining, and mRNA expression in the liver were evaluated. The microbiome was analyzed in mouse cecal contents. In the mouse model, the effects of Lactobacillus in preventing and treating liver fibrosis were different for each microbe species. In case of L. lactis, all models showed preventive and therapeutic effects against liver fibrosis. In microbiome analysis in mouse models administered Lactobacillus, migration and changes in the ratio and composition of the gut microbial community were confirmed. L. lactis and L. rhamnosus showed preventive and therapeutic effects on the progression of liver fibrosis, suggesting that Lactobacillus intake may be a useful strategy for prevention and treatment.

Sufficient Calorie Intake Ameliorates Cognitive Impairment in Alcoholic Liver Disease

( Ye Rin Choi ),( Min Jea Shin ),( Gi Soo Youn ),( Sang Jun Yoon ),( Haripriya Gupta ),( Na Young Lee ),( Hyeong Seop Kim ),( Dong Joon Kim ),( Ki Tae Suk ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Alcoholic liver disease (ALD) is the most common cause of chronic liver disease. And cognitive dysfunction is one of the complications and associated with calorie intake in ALD. However, relation between nutrition and cognitive function has not been fully evaluated. The aim of this study is to explore the effect of diet on cognitive function in ALD. Methods: A total of 43 patients were enrolled and neuropsychological tests assessed according to the nutritional state (BMI<21.7 and BMI≥21.7). In animal study, mice were sub-divided into 4 groups (n=9/group; control (5% EtOH liquid diet), low fat (5% EtOH+low fat diet), high fat (5% EtOH+high fat diet), and high protein (5% EtOH+high protein diet)) for 8 weeks. For the cognitive function, we performed T-maze study weekly before and after alcohol binge. Results: In the comparison of cognitive function (BMI<21.7 and BMI≥21.7), language score of Korea mini-mental state (7.37 ± 1.4 and 7.85 ± 0.4 P=0.04), rey-complex figure (72.0±25.9 and 58.4±33.6, P=0.05), boston naming (11.7±2.7 and 13.0±1.8, P=0.02), forward digit span (6.7±1 .8 and 7.5±1.6, P=0.04), Korean-color word stroop (24.2±26.5 and 43.6±32.4, P=0.006), interference score (33.9±31.9 and 52.3±33.9, P=0.02) showed high scores in BMI≥21.7 group. In the animal study on day 40, all groups shortened the time to find feed (low fat: P=0.004, high fat: P=0.02) compared to the control group. Interestingly, binge drinking mice reduced the time than before trained mice. Conclusions: ALD patients with BMI<21.7 enhance their cognitive dysfunction. Although it needs more studies which correlation of calorie intake and cognitive function, this study indicates that sufficient intake of calories provides major benefits for preventing cognitive dysfunction.

Effect of Korean Red Ginseng on metabolic syndrome

Sang Jun Yoon,Seul Ki Kim,Na Young Lee,Ye Rin Choi,Hyeong Seob Kim,Haripriya Gupta,Gi Soo Youn,Hotaik Sung,Min Jea Shin,Ki Tae Suk 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.3

Metabolic syndrome (MS) refers to a clustering of at least three of the following medical conditions: high blood pressure, abdominal obesity, hyperglycemia, low high-density lipoprotein level, and high serum triglycerides. MS is related to a wide range of diseases which includes obesity, diabetes, insulin resistance, cardiovascular disease, dyslipidemia, or non-alcoholic fatty liver disease. There remains an ongoing need for improved treatment strategies for MS. The most important risk factors are dietary pattern, genetics, old age, lack of exercise, disrupted biology, medication usage, and excessive alcohol consumption, but pathophysiology of MS has not been completely identified. Korean Red Ginseng (KRG) refers to steamed/dried ginseng, traditionally associated with beneficial effects such as anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. KRG has been often used in traditional medicine to treat multiple metabolic conditions. This paper summarizes the effects of KRG in MS and related diseases such as obesity, cardiovascular disease, insulin resistance, diabetes, dyslipidemia, or non-alcoholic fatty liver disease based on experimental research and clinical studies.

Lactobacillus attenuates progression of nonalcoholic fatty liver disease by lowering cholesterol and steatosis

( Na Young Lee ),( Min Jea Shin ),( Gi Soo Youn ),( Sang Jun Yoon ),( Ye Rin Choi ),( Hyeong Seop Kim ),( Haripriya Gupta ),( Sang Hak Han ),( Byoung Kook Kim ),( Do Yup Lee ),( Tae Sik Park ),( Hotai 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.1

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice. Methods: The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [10⁹ colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined. Results: Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P<0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (P<0.05). L. acidophilus (41.0±8.6), L. fermentum (44.3±12.6), and L. plantarum (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (P<0.05). In comparison of steatosis, L. acidophilus (1.9±0.6), L. plantarum (2.4±0.7), and L. paracasei (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (P<0.05). Conclusions: Ingestion of Lactobacillus, such as L. acidophilus, L. fermentum, and L. plantarum, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of Lactobacillus can be considered as a useful strategy for the treatment of NAFLD. (Clin Mol Hepatol 2021;27:110-124)