Gut Microbiota and Drug-Related Liver Injury: Challenges and Perspectives

Abstract

Drug-related liver injury (DILI) is increasing in the incidence of liver injury due to nonviral liver disease and has become a health problem that should not be underestimated. As a hot research topic in recent years, gut microbiota have been studied in various tumors, cardiovascular metabolic diseases, and human immunity. However, there is still a lack of research related to gut microbiota and DILI. It is known that they can influence each other through the regulation of the “gut-liver axis,” and the relationship between them and the possible mechanisms of action are still at the research stage. Human leukocyte antigen (HLA) gene polymorphisms are closely related to the development of DILI, and the gene can also affect changes in the composition of gut microbes. In this paper, we review the possible relationships and mechanisms between DILI and gut microbiota in order to provide new research directions for the prevention and treatment of DILI in the future. In the future, untargeted therapies using antibiotics, probiotics, or FMT will be replaced by personalised and precision medicine approaches, such as bioengineered bacterial strains or drugs that modulate specific bacterial enzymes and metabolic pathways.

Clinical Perspectives of Gut Microbiota in Patients with Chronic Kidney Disease and End-Stage Kidney Disease: Where Do We Stand?

“…GM can mitigate drug-induced liver injury (DILI) and alcoholic liver disease : GM significantly influences drug metabolism and elimination in CKD and renal disease patients [ 94 ]. The capacity of GM to metabolize and modulate drug absorption and distribution contributes to protecting the liver from drug-induced damage [ 95 ].…”

MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation

“…Shreds of evidence show that the chemokines/cytokines secreted by cholangiocytes, especially chemokine (C—C motif) ligand 20 (CCL20), can attract T helper 17 (Th17) lymphocytes to damage bile ducts in liver diseases [31] . But few treatments were found to regulate cytokines secretion or differentiation of Th17 [ 32 , 33 ]. Nevertheless, the secretion of interleukin-17A (IL-17A) from Th17 cells directly activates hepatic stellate cells (HSCs) [ 34 , 35 ], and the levels of circulating IL-17A are associated with the development of mice liver fibrosis [34] .…”