Bifidobacterium bifidum reduces oxidative stress and alters gut flora to mitigate acute liver injury caused by N-acetyl-p-aminophenol.

Abstract

Pharmacologically-induced liver injury from N-acetyl-p-aminophenol (APAP) overdose has become a leading cause of acute liver failure. Extensive research has elucidated the relationship between the intestinal microbiota and the pathophysiology of liver diseases. The growing body of evidence supporting the beneficial effects of probiotics, coupled with their established safety profile, has led to their widespread adoption in clinical practice. Among these, Bifidobacterium bifidum has garnered substantial attention due to its potential hepatoprotective properties, particularly in APAP-induced acute liver injury (AILI). However, the precise therapeutic effects and underlying mechanisms of its potential to alleviate drug-induced liver toxicity remain largely unexplored. To address this knowledge gap, the present study aimed to investigate the role of a new Bifidobacterium bifidum strain CGMCC No. 29,545 isolated from faeces on AILI. A mouse model was constructed through the administration of heat-killed or active B. bifidum CGMCC No. 29,545 preparations via gavage, followed by an intraperitoneal overdose of APAP. The results showed that the active B. bifidum could significantly reverse the increase in plasma transaminase levels and reduce the necrotic area of liver cells in AILI mice. A reduction in oxidative stress accompanied a reduction in this effect. Furthermore, B. bifidum attenuated plasma endotoxin levels and improved colonic inflammation, reducing hepatocyte apoptosis. The 16 S rRNA diversity of intestinal contents suggests that the involvement of B. bifidum in the regulation of the intestinal microbiota also plays a crucial role in the protection against AILI. The above results suggest that the amelioration of multiple injuries due to APAP overprocessing is closely related to active B. bifidum, which was confirmed by heat-killed B. bifidum preparations. Heat-killed B. bifidum preparations did not attenuate the degree of liver injury and oxidative stress caused by APAP treatment. The effects of two different active B. bifidum preparations provide new insights into the protective strategies of active B. bifidum as a probiotic against AILI.