Microbial metabolism dysfunction induced by transarterial chemoembolization aggravates postprocedural liver injury in...

Area of Science:

• Hepatology
• Microbiome Research
• Oncology

Background:

• Transarterial chemoembolization (TACE) is a standard treatment for unresectable hepatocellular carcinoma (HCC).
• TACE-induced liver injury (TACE-LI) is a common complication that compromises patient outcomes.
• The precise mechanisms driving TACE-LI beyond direct organ damage are not fully understood.

Purpose of the Study:

• To investigate the potential role of gut microbiota alterations in the pathogenesis of TACE-LI.
• To identify specific microbial or metabolic factors contributing to TACE-LI.
• To explore therapeutic interventions targeting the gut microbiome to mitigate TACE-LI.

Main Methods:

• Utilized microbial multi-omics analysis, genetically engineered bacteria, and transcriptomics in a rat model.
• Investigated the impact of gut microbiota depletion and fecal microbiota transplantation on TACE-LI severity.
• Quantified Limosilactobacillus reuteri (L. reuteri) and indole-3-lactic acid (ILA) levels in TACE-treated subjects.

Main Results:

• Antibiotic-induced gut dysbiosis and fecal transplants from TACE-treated donors exacerbated TACE-LI.
• TACE treatment significantly reduced L. reuteri abundance and its metabolite ILA in rats and HCC patients.
• Administration of L. reuteri or ILA protected against TACE-LI by inhibiting macrophage-mediated inflammation via the NOD-like receptor protein 3 inflammasome pathway.

Conclusions:

• Gut microbiota disturbance, specifically the deficiency of L. reuteri-derived ILA, is identified as a novel cause of TACE-LI.
• Reduced L. reuteri and ILA levels correlate with increased TACE-LI severity and poorer survival in HCC patients.
• Supplementation with L. reuteri or ILA presents a promising therapeutic strategy to mitigate TACE-LI and improve HCC prognosis.