دورية أكاديمية
Lactobacillus rhamnosus GG combined with inosine ameliorates alcohol-induced liver injury through regulation of intestinal barrier and Treg/Th1 cells.
| العنوان: | Lactobacillus rhamnosus GG combined with inosine ameliorates alcohol-induced liver injury through regulation of intestinal barrier and Treg/Th1 cells. |
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| المؤلفون: | Zhu Y; Department of Infectious Diseases and liver Diseases, Ningbo Medical Centre Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo 315040, China; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou 325025, China., Wang X; Department of General and Gastrointestinal Surgery, The Affiliated Mindong Hospital of Fujian Medical University, Fujian 355000, China., Zhu L; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou 325025, China., Tu Y; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou 325025, China., Chen W; Department of Infectious Diseases and liver Diseases, Ningbo Medical Centre Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo 315040, China., Gong L; Department of Infectious Diseases and liver Diseases, Ningbo Medical Centre Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo 315040, China., Pan T; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou 325025, China., Lin H; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou 325025, China., Lin J; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou 325025, China., Sun H; Department of Infectious Diseases and Liver Diseases, Lishui City People's Hospital, Lishui 323020, China., Ge Y; Department of Infectious Diseases and Liver Diseases, Lishui City People's Hospital, Lishui 323020, China., Wei L; Department of Infectious Diseases and liver Diseases, Ningbo Medical Centre Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo 315040, China., Guo Y; Department of Infectious Diseases and liver Diseases, Ningbo Medical Centre Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo 315040, China., Lu C; Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Centre Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo 315040, China. Electronic address: lucaide@nbu.edu.cn., Chen Y; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou 325025, China. Electronic address: cyp@wmu.edu.cn., Xu L; Department of Infectious Diseases and liver Diseases, Ningbo Medical Centre Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo 315040, China; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou 325025, China. Electronic address: 13587646315@163.com. |
| المصدر: | Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2022 Mar 15; Vol. 439, pp. 115923. Date of Electronic Publication: 2022 Feb 15. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0416575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0333 (Electronic) Linking ISSN: 0041008X NLM ISO Abbreviation: Toxicol Appl Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York, NY : Academic Press Original Publication: New York. |
| مواضيع طبية MeSH: | Chemical and Drug Induced Liver Injury, Chronic* , Lacticaseibacillus rhamnosus*/physiology , Liver Diseases, Alcoholic*/pathology , Liver Diseases, Alcoholic*/prevention & control, Animals ; Ecosystem ; Ethanol/toxicity ; Inflammation ; Inosine ; Male ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; Th1 Cells ; Tight Junction Proteins |
| مستخلص: | Background: Intestinal epithelial barrier disruption and bacterial translocation exacerbates the progression of alcoholic liver disease. Lactobacillus rhamnosus GG (LGG), a probiotic, has been shown benefits in chronic liver disease and in regulating gut dysbiosis. Previous studies showed the protective roles of LGG in ethanol-disrupted gut barrier functions and liver injury. Inosine, a metabolite produced by intestinal bacteria, has the anti-inflammatory and immunregulatory functions. In this study, the synergistic effect of LGG and inosine was investigated in a mouse model of alcohol-induced liver disease (ALD). Methods: Male C57BL/6 mice were fed with a Lieber-DeCarli diet containing 5% alcohol for four weeks to establish a model of alcohol-induced liver injury. LGG or a combination of LGG and inosine were administrated orally to explore a new therapeutic method for alcohol-induced liver disease and to investigate the underlying mechanisms. Liver damage was evaluated by transaminases and pathological changes. Tight junction proteins, composition of the gut microbiome, cytokines, lipopolysaccharides (LPS), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), F4/80+ macrophages, as well as p38, Jun N-terminal kinase (JNK), were determined by qRT-PCR, RNAseq, ELISA, IHC and western blot. Regulatory T (Treg) cells were characterized by positive staining of CD4, CD25 and Foxp3 using flow cytometry. IFN-γ-producing CD4 + T (Th1) cells were examined by intracellular cytokine staining. Results: Alcohol consumption induced elevated liver enzymes, steatosis and inflammation, while LGG combined with inosine treatment was more significant to ameliorate these symptoms compared with LGG alone. When LGG combined with inosine were administered to ALD mice, intestinal microecology significantly improved reflected by intestinal villi and tight junction proteins recovery and the restoration of intestinal flora. Combined therapy inhibited phosphorylation of p38 and JNK to alleviate hepatic inflammation. Moreover, flow cytometry analysis showed that long-term excessive alcohol consumption reduced Tregs population while increased Th1 population, which was restored by a combination of LGG and inosine treatment. Conclusions: The findings from the study indicate that the combined LGG and inosine treatment ameliorates ALD by improving the gut ecosystem, intestinal barrier function, immune homeostasis and liver injury. (Copyright © 2022. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Alcoholic liver disease; Gut microbiota; IFN-γ–producing CD4(+) T cells; Inosine; Lactobacillus rhamnosus GG; Regulatory T cells |
| المشرفين على المادة: | 0 (Tight Junction Proteins) 3K9958V90M (Ethanol) 5A614L51CT (Inosine) |
| تواريخ الأحداث: | Date Created: 20220217 Date Completed: 20220429 Latest Revision: 20221207 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.taap.2022.115923 |
| PMID: | 35176292 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-0333 |
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| DOI: | 10.1016/j.taap.2022.115923 |