Protective effect of Lactobacillus salivarius Li01 on thioacetamide‐induced acute liver injury and hyperammonaemia

Abstract

The gut microbiota plays pivotal roles in liver disease onset and progression. The protective effects of Lactobacillus salivarius Li01 on liver diseases have been reported. In this study, we aimed to detect the protective effect of L. salivarius Li01 on thioacetamide (TAA)-induced acute liver injury and hyperammonaemia. C57BL/6 mice were separated into three groups and given a gavage of L. salivarius Li01 or phosphate-buffered saline for 7 days. Acute liver injury and hyperammonaemia were induced with an intraperitoneal TAA injection. L. salivarius Li01 decreased mortality and serum transaminase levels and improved histological liver damage caused by TAA. Serum inflammatory cytokine and chemokine and lipopolysaccharide-binding protein (LBP) concentrations, nuclear factor jB (NFjB) pathway activation and macrophage and neutrophil infiltration into the liver were significantly alleviated by L. salivarius Li01. L. salivarius Li01 also reinforced gut barrier and reshaped the perturbed gut microbiota by upregulating Bacteroidetes and Akkermansia richness and downregulating Proteobacteria, Ruminococcaceae_UCG_014 and Helicobacter richness. Plasma and faecal ammonia levels declined noticeably in the Li01 group, accompanied by improvements in cognitive function, neuro-inflammation and relative brain-derived neurotrophic factor (BDNF) gene expression. Our results indicated that L. salivarius Li01 could be considered a potential probiotic in acute liver injury and hepatic encephalopathy (HE).

Dose-Dependent Relationship between Protection of Thioacetamide-Induced Acute Liver Injury and Hyperammonemia and Concentration of Lactobacillus salivarius Li01 in Mice

“…However, very few studies have been conducted that examine the dose-response relation. Therefore, based on the research of Yang et al ( 29 ), the protective effect of different concentrations of L. salivarius Li01 on TAA-induced acute liver injury and hyperammonemia was explored in this study.…”

“…We found the overall trend of ammonia levels in intestinal contents and blood to decrease with the increase of intervention concentration of Lactobacillus salivarius Li01. Yang et al proved that L. salivarius Li01 reduced fecal ammonia, and a correlation has been established between the concentrations of blood ammonia, fecal ammonia, and fecal microbiota ( 29 ). This study demonstrated that pretreatment of mice with different concentrations of L. salivarius Li01 leads to different amounts of L. salivarius Li01 colonizing their lumen, changes the composition and function of intestinal microbial structure, and therefore, affects their intestinal ammonia metabolism.…”

“…In addition, LPS from Gram-negative bacteria played a pivotal role that led to deteriorated condition of group PC, which, in combination with brain intoxication caused by high ammonia levels, resulted in a low survival rate in this group. Conditions improved when the mice were pretreated with L. salivarius Li01 in groups A and B due to their ability to protect the intestinal barrier, alleviate liver damage, and decrease the plasma and fecal ammonia levels ( 29 , 32 ). However, when the concentration of L. salivarius Li01 continued to increase, the protective effect of the probiotic started to dissipate, and the adverse effects started to emerge.…”

“…Recently, Yang et al ( 29 ) found that in the mouse model with thioacetamide-induced acute liver injury and hyperammonemia, L. salivarius Li01 had a protective effect, therefore improving the survival rate of the mice. Apart from that, L. salivarius Li01, which is isolated from the feces of healthy individuals, has also been proved to have bile salt resistance ( 30 ), ameliorates acute liver injury induced by d -galactosamine ( 31 ), and prevents CCl 4 -induced cirrhosis by protecting the intestinal barrier in rats ( 32 ).…”

“…Therefore, based on the research of Yang et al ( 29 ), this study investigated the protective effect that was produced by L. salivarius Li01 at different concentrations in mice with TAA-induced acute liver injury and hyperammonemia.…”