Dietary modulation of gut microbiota affects susceptibility to drug-induced liver injury
Han Pan,
Delei Song,
Zhiyi Wang,
Xin Yang,
Pei Luo,
Wei Li,
Yan Li,
Mengxue Gong,
Chenhong Zhang
Affiliations
Han Pan
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Delei Song
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Zhiyi Wang
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Xin Yang
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Pei Luo
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Wei Li
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Yan Li
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Mengxue Gong
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
Chenhong Zhang
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
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.
