The rising incidence of drug-induced liver injury (DILI) parallels contemporary dietary shifts that have transformed the composition of human gut microbiota. The relationship between these phenomena remains unknown. Here, it is unveiled that a high fiber diet (HFiD) provides substantial protection against DILI, whereas a western style diet (WSD) significantly exacerbates DILI. Gut microbiota transplantation further confirms these differing outcomes are mediated by diet-induced variations in gut microbiota. Mechanistically, Lactobacillus acidophilus, enriched by HFiD, alleviates DILI through its metabolite indole-3-lactic acid (ILA), which activates the AhR/Nrf2 signaling pathway, thus enhancing hepatocellular antioxidant defenses and detoxification capacity. In the clinical intervention of subjects with prediabetes (N = 330), dietary fiber intervention enriches intestinal L. acidophilus, elevates serum ILA levels, and improves liver function. Conversely, WSD induces disturbance in bile acid metabolism and dysbiosis in gut microbiota, which impairs the intestinal barrier and facilitates the translocation of lipopolysaccharides (LPS) to the liver, thus triggering inflammatory responses and exacerbating DILI. These results demonstrate that dietary patterns significantly influence the onset of DILI by modulating gut microbiota. This novel insight expands the understanding of DILI risk factors and highlights the potential of dietary modifications as a preventive strategy against DILI.

中文翻译：

---

肠道菌群的饮食调节会影响对药物性肝损伤的易感性。


药物性肝损伤 （DILI） 发病率的上升与改变人类肠道微生物群组成的当代饮食转变相呼应。这些现象之间的关系仍然未知。在这里，揭示了高纤维饮食 （HFiD） 对 DILI 提供了实质性保护，而西式饮食 （WSD） 会显着加剧 DILI。肠道微生物群移植进一步证实这些不同的结果是由饮食诱导的肠道微生物群变化介导的。从机制上讲，富含 HFiD 的嗜酸乳杆菌通过其代谢物吲哚-3-乳酸 （ILA） 缓解 DILI，ILA 激活 AhR/Nrf2 信号通路，从而增强肝细胞抗氧化防御和解毒能力。在糖尿病前期受试者 （N = 330） 的临床干预中，膳食纤维干预丰富了嗜酸乳杆菌肠道，提高了血清 ILA 水平，并改善了肝功能。相反，WSD 会诱导胆汁酸代谢紊乱和肠道菌群失调，从而损害肠道屏障并促进脂多糖 （LPS） 易位到肝脏，从而引发炎症反应并加剧 DILI。这些结果表明，饮食模式通过调节肠道微生物群显着影响 DILI 的发生。这种新颖的见解扩大了对 DILI 风险因素的理解，并强调了饮食调整作为预防 DILI 策略的潜力。