Idiosyncratic Drug-Induced Liver Injury and Amoxicillin-Clavulanate: Spotlight on Gut Microbiota, Fecal Metabolome and Bile Acid Profile in Patients.

Autores de IIS La Fe

• Polina Soluyanova Tsaregorodtseva

  Autor

• 

  Ramiro Jover Atienza

  Autor

Participantes ajenos a IIS La Fe

• Roman-Saguillo, Sara
• Quinones Castro, Raisa
• Juarez-Fernandez, Maria
• Stephens, Camilla
• Robles-Diaz, Mercedes
• Jorquera Plaza, Francisco
• Gonzalez-Gallego, Javier
• Martinez-Florez, Susana
• Garcia-Mediavilla, Maria Victoria
• Nistal, Esther
• Sanchez-Campos, Sonia

Grupos

• Hepatología experimental y Trasplante hepático

• Unidad Mixta de Investigación en Hepatología Experimental

Abstract

Several hepatic disorders are influenced by gut microbiota, but its role in idiosyncratic drug-induced liver injury (iDILI), whose main causative agent is amoxicillin-clavulanate, remains unknown. This pioneering study aims to unravel particular patterns of gut microbiota composition and associated metabolites in iDILI and iDILI patients by amoxicillin-clavulanate (iDILI-AC). Thus, serum and fecal samples from 46 patients were divided into three study groups: healthy controls (n = 10), non-iDILI acute hepatitis (n = 12) and iDILI patients (n = 24). To evaluate the amoxicillin-clavulanate effect, iDILI patients were separated into two subgroups: iDILI non-caused by amoxicillin-clavulanate (iDILI-nonAC) (n = 18) and iDILI-AC patients (n = 6). Gut microbiota composition and fecal metabolome plus serum and fecal bile acid (BA) analyses were performed, along with correlation analyses. iDILI patients presented a particular microbiome profile associated with reduced fecal secondary BAs and fecal metabolites linked to lower inflammation, such as dodecanedioic acid and pyridoxamine. Moreover, certain taxa like Barnesiella, Clostridia UCG-014 and Eubacterium spp. correlated with significant metabolites and BAs. Additionally, comparisons between iDILI-nonAC and iDILI-AC groups unraveled unique features associated with iDILI when caused by amoxicillin-clavulanate. In conclusion, specific gut microbiota profiles in iDILI and iDILI-AC patients were associated with particular metabolic and BA status, which could affect disease onset and progression.

Keywords

• drug-induced liver disease; amoxicillin-clavulanate; gut microbiota; bile acids; fecal metabolome