Probiotics and their beneficial effects on alcohol-induced liver injury in a rat model: the role of fecal microbiota

Abstract

Abstract Background Current therapies for alcohol-induced liver injury are of limited efficacy and associated with significant side effects. With the proposed pathophysiology of alcohol-induced liver injury to be related to deranged gut microbiota, we hypothesized that probiotics would have beneficial effects in attenuating alcohol-induced liver injury. Methods Twenty-four male Sprague-Dawley rats were divided into 4 groups: control group, alcohol group, Lactobacillus plantarum group, and mixed-strain probiotics group. After 4 weeks, all rats were sacrificed, and blood samples were analyzed for ALT, lipopolysaccharide level (LPS), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Liver tissues were processed for histopathology, malondialdehyde (MDA) level and immunohistochemistry for toll-like receptors 4 (TLR-4). Stool samples were collected, and 16S rRNA sequencing was used to analyze the fecal microbiota. Results Liver histopathology showed the presence of significant hepatocyte ballooning in the alcohol group as compared with the control group, and the treatment with L. plantarum or mixed-strain probiotics alleviated these changes. Significant elevation of serum ALT, LPS, IL-6, and TNF-α, hepatic MDA levels, and hepatic TLR-4 expression were observed in alcohol-fed rats as compared with control rats. The administration of L. plantarum or mixed-strain probiotics restored these changes to the levels of control rats. The relative abundance of fecal bacteria at genus level showed a significant reduction in Allobaculum, Romboutsia, Bifidobacterium, and Akkermansia in the alcohol group as compared with the control group. In probiotics-treated rats, significant increases in Allobaculum and Bifidobacterium were observed, while the relative abundance of Romboutsia and Akkermansia was unchanged compared to the alcohol group. A reduction in alpha diversity was observed in alcohol-treated rats, whereas the improvement was noted after probiotic treatment. Conclusions The treatment with Lactobacillus, whether as single-, or mixed-strain probiotics, was beneficial in reducing the severity of alcohol-induced liver injury likely through the increase in beneficial bacteria, and the reduction of inflammatory responses, and oxidative stress.