早年接触抗生素会加重与肝细胞癌相关的代谢功能障碍性脂肪肝。

IF 3.4 2区 医学 Q2 ONCOLOGY
Panpan Tian, Xinyu Tian, Lifen Gao, Chunhong Ma, Xiaohong Liang
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引用次数: 0

摘要

背景:代谢功能障碍相关性脂肪性肝病(MASLD)相关性肝细胞癌(HCC)正成为全球医疗保健领域日益关注的问题。生命早期的肠道微生物群在维持健康方面发挥着至关重要的作用。然而,人们对生命早期肠道微生物群失调对MASLD-HCC进展的影响仍缺乏足够的了解:本研究调查了链脲佐菌素和高脂饮食(STZ-HFD)诱导的小鼠模型中早期肠道微生物群在 MASLD-HCC 发病中的作用。我们记录了小鼠的体重和寿命,并每月动态监测血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、甘油三酯(TG)、总胆固醇(T-CHO)和血糖的水平。此外,我们还通过流式细胞术检测了肝脏中存在的各种免疫细胞,如T细胞、B细胞、NK细胞、NKT细胞、αβT细胞、γδT细胞、巨噬细胞和MDSC细胞,并对对照组和早期抗生素暴露小鼠(early-Abx)MASLD-HCC小鼠的肝组织进行了基于液相色谱质谱法(LC-MS)的分析:结果:我们发现早期抗生素暴露小鼠的肿瘤负荷更严重,并进一步证实肝细胞和免疫细胞均受到干扰。重要的是,早期抗生素暴露会改变肝脏代谢谱,尤其是甘油磷脂和脂质积累。此外,早期接触抗生素的小鼠表现出糖代谢紊乱,并出现胰岛素抵抗:总之,我们的研究结果表明,早期抗生素暴露会持续损害肝细胞、免疫稳态和代谢物,从而加速 MASLD-HCC 的进展,这凸显了早期微生物群在 MASLD-HCC 发展过程中的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma.

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.

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来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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