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- Title
Ampicillin exacerbates acetaminophen‐induced acute liver injury by inducing intestinal microbiota imbalance and butyrate reduction.
- Authors
Li, Zhan‐Ming; Kong, Chao‐Yue; Mao, Yu‐Qin; Huang, Jia‐Ting; Chen, Hui‐Ling; Han, Bing; Wang, Li‐Shun
- Abstract
Background and Aims: Antibiotics (ATBx) and acetaminophen (APAP) are widely used worldwide. APAP is the most common cause of acute liver injury (ALI) and might be used in combination with ATBx in clinics. However, the impact of ATBx on APAP‐induced ALI has rarely been studied. Methods: First, we compared the effects of seven ATBx on APAP‐induced ALI. Then, we analysed faecal, serum and liver samples to investigate the impact of the gut microbiota on this process. Finally, we assessed the role of short‐chain fatty acids in this process. Results: In this work, we found that the ALI was significantly aggravated in the mice treated with ampicillin (Amp) instead of other ATBx. Amp exposure reduced the diversity and altered the composition of gut microbiota. The altered gut microbiota aggravated APAP‐induced ALF, which was proven by faecal microbiota transplantation from ATBx‐treated mice. Metagenomic analysis showed a significantly decreased Lactobacillus abundance in Amp‐treated mice. Gavage with Lactobacillus, especially Lactobacillus rhamnosus, significantly reversed the severer ALF induced by APAP and Amp. Moreover, Lactobacillus supplementation increased butyrate‐producing clostridia and lowered butyrate levels in Amp‐treated mice. In accordance, butyrate supplementation could also alleviate Amp‐aggravated ALI. In addition, inhibition of nuclear factor erythroid 2–related factor 2 counteracted the protective effect of butyrate on aggravated ALI induced by Amp and APAP. Conclusion: Together, this study revealed a potential health impact of Amp that may exacerbate liver damage when co‐exposed to excess APAP.
- Subjects
NUCLEAR factor E2 related factor; GUT microbiome; FECAL microbiota transplantation; LIVER injuries; INTESTINAL injuries
- Publication
Liver International, 2023, Vol 43, Issue 4, p865
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/liv.15512