Interplay Between Drug-Induced Liver Injury and Gut Microbiota: A Comprehensive Overview

Abstract

Drug-induced liver injury is a prevalent severe adverse event in clinical settings, leading to increased medical burdens for patients and presenting challenges for the development and commercialization of novel pharmaceuticals. Research has revealed a close association between gut microbiota and drug-induced liver injury in recent years. However, there has yet to be a consensus on the specific mechanism by which gut microbiota is involved in drug-induced liver injury. Gut microbiota may contribute to drug-induced liver injury by increasing intestinal permeability, disrupting intestinal metabolite homeostasis, and promoting inflammation and oxidative stress. Alterations in gut microbiota were found in drug-induced liver injury caused by antibiotics, psychotropic drugs, acetaminophen, antituberculosis drugs, and antithyroid drugs. Specific gut microbiota and their abundance are associated closely with the severity of drug-induced liver injury. Therefore, gut microbiota is expected to be a new target for the treatment of drug-induced liver injury. This review focuses on the association of gut microbiota with common hepatotoxic drugs and the potential mechanisms by which gut microbiota may contribute to the pathogenesis of drug-induced liver injury, providing a more comprehensive reference for the interaction between drug-induced liver injury and gut microbiota.

Keywords: Drug-Induced Liver Injury; Gut Microbiota; Hepatotoxic Drug; Mechanisms.

Figure 1

GM participates in the mechanism of DILI through LPS. The drugs can disrupt the balance of GM, leading to increased levels of LPS, which in turn trigger intestinal inflammation and increased intestinal permeability. This subsequently results in intestinal leakage, allowing the LPS produced in the intestines to migrate to the liver, ultimately causing metabolic disorders and DILI. β-glucuronidase is an enzyme capable of converting drugs into their active forms. Liver injury leads to reduced β-glucuronidase activity, thereby affecting the drug metabolism process. RegIIIβ and RegIIIɣ are lectins that regulate bacterial density in GM and participate in the host's innate immune response to GM. GM, gut microbiota.