Yang Yong, He Yanzhao, Yang Xiaodan, Qiao Yuyu, Yi Gaoqin, Fan Weiping, Liu Hongli, Tong Mingwei
School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, China.
Key Laboratory of Cellular Physiology, Ministry of Education, and Shanxi Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan 030001, China.
ACS Pharmacol Transl Sci. 2024 Jan 18;7(2):432-444. doi: 10.1021/acsptsci.3c00276. eCollection 2024 Feb 9.
Nonalcoholic fatty liver disease (NAFLD) is a liver disease characterized by hepatic steatosis, inflammation, and fibrosis, as well as gut dysbiosis. No approved effective therapeutic medicine is available to date for NAFLD. Helminth therapy is believed to be a novel direction and therapeutic strategy for NAFLD. Our previous study showed that -derived antigens () had the potential for partially alleviating obesity via regulating gut microbiota. However, the effect of on NAFLD remains unclear. In this study, high-fat diet (HFD)-induced model mice were treated with and microbiota transplantation experiments, and alterations in the pathogenesis of nonalcoholic liver disease were assessed. The results showed that markedly reduced hepatic steatosis, improved insulin resistance, and regulated the abnormal expression of hepatic lipid-related genes. Of note, ameliorated hepatic inflammation by decreasing pro-inflammatory TNF-α and IL-1β, suppressing hepatic macrophage infiltration, as well as promoting M2 macrophage polarization. Moreover, reversed gut dysbiosis, as especially indicated by an increase in beneficial bacteria (e.g., and ). Furthermore, our study found that reduced LPS hepatic translocation and hepatic TLR4/NF-κB signaling, which further contributed to inhibiting hepatic inflammation. In addition, inhibited hepatic oxidative stress involving Nrf2/NQO-1 signaling. Microbiota transplantation showed that -altered microbiota is sufficient to confer protection against NAFLD in HFD-induced mice. Overall, these findings suggest that involving gut-liver axis and Nrf2/NQO-1 signaling is a novel promising candidate for NAFLD treatment. restores intestinal microbiota and intestinal barrier to inhibit bacteria and LPS translocation into the liver, contributing to reduce inflammation, oxidative stress, and hepatic steatosis in the liver of NAFLD mice. The effects were attributed to, at least in part, the inactivation of NF-κB pathway and the activation of Nrf-2/NQO-1 pathway. This study provides new insights for understanding immune modulation by -derived products as well as the potential application of TsAg as a modality for NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种以肝脂肪变性、炎症、纤维化以及肠道菌群失调为特征的肝脏疾病。迄今为止，尚无获批的针对NAFLD的有效治疗药物。蠕虫疗法被认为是NAFLD的一种新方向和治疗策略。我们之前的研究表明，[具体名称]衍生抗原（[具体名称]）有通过调节肠道微生物群部分缓解肥胖的潜力。然而，[具体名称]对NAFLD的影响仍不清楚。在本研究中，用[具体名称]和微生物群移植实验处理高脂饮食（HFD）诱导的模型小鼠，并评估非酒精性肝病发病机制的改变。结果表明，[具体名称]显著降低了肝脂肪变性，改善了胰岛素抵抗，并调节了肝脏脂质相关基因的异常表达。值得注意的是，[具体名称]通过降低促炎细胞因子TNF-α和IL-1β、抑制肝巨噬细胞浸润以及促进M2巨噬细胞极化来改善肝脏炎症。此外，[具体名称]逆转了肠道菌群失调，尤其表现为有益菌（如[具体有益菌名称1]和[具体有益菌名称2]）的增加。此外，我们的研究发现，[具体名称]减少了LPS的肝脏转运以及肝脏TLR4/NF-κB信号传导，这进一步有助于抑制肝脏炎症。另外，[具体名称]抑制了涉及Nrf2/NQO-1信号传导的肝脏氧化应激。微生物群移植表明，[具体名称]改变的微生物群足以在HFD诱导的小鼠中赋予对NAFLD的保护作用。总体而言，这些发现表明，涉及肠-肝轴和Nrf2/NQO-1信号传导的[具体名称]是NAFLD治疗的一种新的有前景的候选物。[具体名称]恢复肠道微生物群和肠道屏障以抑制细菌和LPS向肝脏的转运，有助于减少NAFLD小鼠肝脏中的炎症、氧化应激和肝脂肪变性。这些作用至少部分归因于NF-κB途径的失活和Nrf-2/NQO-1途径的激活。本研究为理解[具体名称]衍生产物的免疫调节以及TsAg作为NAFLD一种治疗方式的潜在应用提供了新的见解。
