THE EFFECT OF A PROBIOTIC ON HEPATIC STEATOSIS

益生菌对肝脏脂肪变性的影响

• 批准号: 7378910
• 负责人: STEVEN F SOLGA
• 金额: $ 0.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378910
• 关键词: EFFECT; PROBIOTIC; HEPATIC; STEATOSIS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States. NAFLD includes a spectrum of hepatic pathology that ranges from fatty liver (steatosis) at the most clinically indolent extreme, to cirrhosis at the opposite extreme where most liver specific morbidity and mortality occurs. Indeed, NAFLD is now thought to be responsible for most of what was once classified as "cryptogenic cirrhosis." Cryptogenic cirrhosis accounts for half of the annual liver-related deaths in the United States. The study of NAFLD has been hindered by the lack of an easily measurable, clinically relevant outcome measure. Safe, inexpensive, well-tolerated treatments for NAFLD are greatly needed. While the basic mechanisms that initiate hepatic steatosis and subsequent progression to cirrhosis remain unknown, recent breakthroughs using animal models have advanced understanding and provide hope for the development of effective treatments. Based on extensive work in our own laboratory, our OVERALL HYPOTHESIS is that alcohol and lipopolysacchride (LPS) production by intestinal bacterial overgrowth (IBO) cause inflammatory signaling in the liver that leads to hepatic insulin resistance and NAFLD. To evaluate this possibility, we treated a murine model of NAFLD with probiotics or anti-tumor necrosis factor a (TNFa) antibodies. We hypothesized that either probiotics or anti-TNFa would decrease inflammation and improve insulin resistance and hepatic steatosis. Indeed, both treatments decreased activation of well-defined molecular inflammatory pathways and improved steatosis by biopsy. This exciting preliminary data provides rationale for studying probiotics in humans. Therefore, this project has a single SPECIFIC AIM: to determine if probiotic therapy can decrease hepatic steatosis in humans with NAFLD.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。非酒精性脂肪肝病（NAFLD）是美国慢性肝病的最常见原因。 NAFLD包括一系列肝病理学，范围从最临床上懒惰的极端脂肪肝（脂肪变性）到大多数肝脏特异性发病率和死亡率的相反极端的肝硬化。的确，现在认为NAFLD是曾经被归类为“隐性肝硬化”的大多数造成的。隐性肝硬化是美国年度肝脏相关死亡的一半。由于缺乏易于测量的临床相关结果度量，NAFLD的研究受到了阻碍。非常需要安全，廉价，耐受性良好的NAFLD治疗方法。尽管启动肝脂肪变性并随后发展为肝硬化的基本机制仍然未知，但使用动物模型的最近突破具有深刻的理解，并为有效治疗的发展提供了希望。基于我们自己的实验室中的广泛工作，我们的总体假设是，肠道细菌过度生长（IBO）的酒精和脂多亚酸（LPS）产生会导致肝脏炎症信号传导，从而导致肝胰岛素抵抗和NAFLD。为了评估这种可能性，我们用益生菌或抗肿瘤坏死因子A（TNFA）抗体处理了NAFLD的鼠模型。我们假设益生菌或抗TNFA可以减轻炎症并改善胰岛素抵抗和肝脂肪变性。实际上，两种处理都降低了定义明确的分子炎症途径的激活，并通过活检改善了脂肪变性。这种令人兴奋的初步数据为研究人类益生菌提供了理由。因此，该项目具有一个特定的目的：确定益生菌治疗是否可以减少NAFLD人类的肝脂肪变性。