Antibiotic exposure exacerbates acute-on-chronic liver failure via gut microbiota imbalance and secondary liver lesion.

Survival rates were significantly lower in ACLF patients exposed to antibiotics compared to matched non-exposed controls at multiple time points.

• Twenty-three ACLF patients with antibiotic exposure were matched to 46 controls without antibiotic exposure in a retrospective matched study design.
• Survival rates at 4, 12, and 24 weeks were all significantly lower in the antibiotic exposure group than in the non-exposure group.
• The study design was a retrospective matched study, with a 1:2 ratio of exposed to non-exposed patients.

Antibiotic exposure resulted in more severe hepatitis and higher alanine transaminase (ALT) levels in the ACLF rat model.

• In the ACLF rat model, hepatitis in the antibiotic-exposure group became more severe than in the non-exposure group.
• Alanine transaminase levels were higher in the antibiotic-exposed rat group compared to the non-exposed group.
• The rat model findings corroborated the clinical findings of adverse outcomes associated with antibiotic exposure.

Gut microbiota diversity was decreased in ACLF patients with antibiotic exposure, with specific changes in bacterial family proportions.

• The proportions of Enterococcaceae and Peptostreptococcaceae were increased in antibiotic-exposed ACLF patients.
• The proportions of Lachnospiraceae, Bifidobacteriaceae, and Bacteroidaceae were decreased in antibiotic-exposed ACLF patients.
• Gut microbiota was sequenced using the Illumina MiSeq platform in both ACLF patients and the rat model.

In the ACLF rat model, antibiotic exposure induced broad bacterial eradication and led to Klebsiella becoming the dominant microorganism.

• Antibiotic exposure induced eradication of both Gram-positive and Gram-negative bacteria in the rat model.
• Klebsiella became the dominant microorganism following antibiotic-induced dysbiosis in the rat model.
• This shift in microbial dominance toward Klebsiella may represent a mechanism contributing to secondary liver lesion.

The study hypothesized and found evidence that antibiotic exposure in ACLF alters gut microbiota in ways that negatively affect ACLF outcomes.

• The study used both a retrospective matched clinical cohort and an ACLF rat model to investigate the relationship between antibiotic exposure, gut microbiota, and outcomes.
• The proposed underlying mechanism for worsened outcomes is dysbiosis in the gut microbiota leading to secondary liver lesion.
• The correlation between antibiotic exposure and adverse outcomes in ACLF patients was described as previously controversial with unclear underlying mechanism.