Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma
Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) asscociated hepatocellular carcinoma (HCC) is becoming a growing concern in global healthcare. The early-life gut microbiota plays a crucial role in maintaining healthy. However, the impact of early-life gut microbi...
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BMC
2024-11-01
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| Online Access: | https://doi.org/10.1186/s12885-024-13136-2 |
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| author | Panpan Tian Xinyu Tian Lifen Gao Chunhong Ma Xiaohong Liang |
| author_facet | Panpan Tian Xinyu Tian Lifen Gao Chunhong Ma Xiaohong Liang |
| author_sort | Panpan Tian |
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| description | Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) asscociated hepatocellular carcinoma (HCC) is becoming a growing concern in global healthcare. The early-life gut microbiota plays a crucial role in maintaining healthy. However, the impact of early-life gut microbiota dysbiosis on the advancement of MASLD-HCC remains inadequately understood. Methods In the present study, we investigated the role of early-life gut microbiota in the development of MASLD-HCC in streptozotocin and high-fat diet (STZ-HFD) induced mouse model. We recorded the body weight and lifespan, and dynamically monitored the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (T-CHO) and blood glucose in the serum monthly. In addition, we examined various immune cells present in the liver, such as T cells, B cells, NK cells, NKT cells, αβT cells, γδT cells, macrophage and MDSC cells by flow cytometry and conducted liquid chromatography mass spectrometry (LC–MS) based analysis on liver tissue from control and early-life antibiotic exposure mice (early-Abx) MASLD-HCC mice. Results We found that early-Abx mice suffered from more severe tumor burden and further confirmed that hepatocytes and immune cells were all disturbed. Importantly, early-life antibiotic exposure alters the liver metabolic profiling especially glycerophospholipids and lipid accumulation. Furthermore, mice exposed to antibiotics in early-life showed disturbances in glucose metabolism and developed insulin resistance. Conclusions Collectively, our findings revealed that early-life antibiotic exposure accelerated the progression of MASLD-HCC by impairing the hepatocytes, immune homeostasis and metabolites persistently, highlighting the importance of the early-life microbiota in the development of MASLD-HCC. |
| format | Article |
| id | doaj-art-c72ccdfc49cc4198aa65072818ba089a |
| institution | OA Journals |
| issn | 1471-2407 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-c72ccdfc49cc4198aa65072818ba089a2025-08-20T02:13:28ZengBMCBMC Cancer1471-24072024-11-0124111210.1186/s12885-024-13136-2Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinomaPanpan Tian0Xinyu Tian1Lifen Gao2Chunhong Ma3Xiaohong Liang4Department of Clinical Laboratory, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing UniversityDepartment of Clinical Laboratory, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College of Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College of Shandong UniversityKey Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College of Shandong UniversityAbstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) asscociated hepatocellular carcinoma (HCC) is becoming a growing concern in global healthcare. The early-life gut microbiota plays a crucial role in maintaining healthy. However, the impact of early-life gut microbiota dysbiosis on the advancement of MASLD-HCC remains inadequately understood. Methods In the present study, we investigated the role of early-life gut microbiota in the development of MASLD-HCC in streptozotocin and high-fat diet (STZ-HFD) induced mouse model. We recorded the body weight and lifespan, and dynamically monitored the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (T-CHO) and blood glucose in the serum monthly. In addition, we examined various immune cells present in the liver, such as T cells, B cells, NK cells, NKT cells, αβT cells, γδT cells, macrophage and MDSC cells by flow cytometry and conducted liquid chromatography mass spectrometry (LC–MS) based analysis on liver tissue from control and early-life antibiotic exposure mice (early-Abx) MASLD-HCC mice. Results We found that early-Abx mice suffered from more severe tumor burden and further confirmed that hepatocytes and immune cells were all disturbed. Importantly, early-life antibiotic exposure alters the liver metabolic profiling especially glycerophospholipids and lipid accumulation. Furthermore, mice exposed to antibiotics in early-life showed disturbances in glucose metabolism and developed insulin resistance. Conclusions Collectively, our findings revealed that early-life antibiotic exposure accelerated the progression of MASLD-HCC by impairing the hepatocytes, immune homeostasis and metabolites persistently, highlighting the importance of the early-life microbiota in the development of MASLD-HCC.https://doi.org/10.1186/s12885-024-13136-2Early-life antibiotic exposureMetabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinomaImmune homeostasisMetabolites |
| spellingShingle | Panpan Tian Xinyu Tian Lifen Gao Chunhong Ma Xiaohong Liang Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma BMC Cancer Early-life antibiotic exposure Metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma Immune homeostasis Metabolites |
| title | Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma |
| title_full | Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma |
| title_fullStr | Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma |
| title_full_unstemmed | Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma |
| title_short | Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma |
| title_sort | early life antibiotic exposure aggravate the metabolic dysfunction associated steatotic liver disease associated hepatocellular carcinoma |
| topic | Early-life antibiotic exposure Metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma Immune homeostasis Metabolites |
| url | https://doi.org/10.1186/s12885-024-13136-2 |
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