Previous studies have revealed that the probiotic Clostridium butyricum (C. butyricum) can attenuate cirrhosis in chronic non-alcoholic liver disease. However, the effects of C. butyricum on acute liver injury (ALI) remain unclear. Therefore, the present study aims to examine the hepatoprotective effects and the underlying mechanisms employed by C. butyricum in a carbon tetrachloride (CCl)-induced ALI murine model. Here, we evaluated the survival rate and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), anti-oxidants, cytokines and the gut microbiota to elucidate the potential mechanisms by which C. butyricum is hepatoprotective. Our results show that five days of prophylactic C. butyricum treatment significantly reduced mortality by 40% and decreased the CCl-induced levels of ALT and AST in the serum of these mice. Additionally, prophylactic treatment with C. butyricum increased the activity of both superoxide dismutase (SOD) and catalase (CAT), and substantially reduced malondialdehyde (MDA) levels, which were deteriorated in the untreated ALI mice compared to normal control mice. Furthermore, C. butyricum up-regulated the nuclear factor (erythroid-derived 2)-like 2 (NRF2) content. CCl-induced mice also exhibited considerable increases of phosphorylation of nuclear factor-kappa B (NF-κB) p65 and pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). However, the inflammatory responses of the liver induced by CCl were significantly alleviated by C. butyricum pretreatment. Additionally, we found that interleukin-10 (IL-10), an anti-inflammatory mediator, was increased in the C. butyricum-pretreated group. Microbiota analysis in these mice revealed crosstalk between the gut microbial metabolites and ALI. The intestinal flora was changed by CCl administration and was shifted by the probiotic C. butyricum toward more beneficial bacteria, particularly the Clostridia orders, which are the known producers of the anti-inflammatory and anti-oxidative metabolite butyrate. In conclusion, we found that the intestinal flora changes after the intraperitoneal injection of CCl. We also offer novel insights into the mechanism by which probiotic C. butyricum pretreatment alleviates the CCl-induced inflammation and oxidative stress of the liver via the modulation of NRF2, NF-κB p65, IL-10 and the intestinal microbiota in mice.
Butyrate is one of the most abundant short-chain fatty acids produced by intestinal bacteria. In the present study, the action of butyrate on chronic gastric mucosa lesions was investigated, as well as its underlying mechanism in mice. Male mice from the Institute of Cancer Research were randomly divided into three groups: Sham, model and butyrate groups. Butyrate was administered intragastrically for 7 days to butyrate group mice following the establishment of a gastric ulcer model. Hematoxylin and eosin staining, immunohistochemical analysis, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction were used to determine the therapeutic effects and molecular mechanism of butyrate treatment. The findings demonstrated that butyrate induced a marked shift in superoxide dismutase and catalase activities, along with a decrease in malondialdehyde levels, thereby attenuating oxidative stress. Furthermore, butyrate decreased the levels of pro-inflammatory cytokines interleukin-1β, tumour necrosis factor-α and leukotriene B4, which helped combat inflammatory responses. Moreover, butyrate treatment exerted remarkable positive influences that mediate an increase in 6-keto-PGF-1α (a degradation product of prostacyclin), trefoil factor 2, MUC5AC and fibroblast growth factor-7 levels to promote gastric mucosal repair. The expression of specific receptor GPR109A for butyrate was upregulated, with no significant difference noted in the expression of GPR43 or GPR41. Overall, the present findings revealed that butyrate exerted therapeutic effects by upregulating mucosal repair factors and stimulating protective responses against oxidation and inflammation. GPR109A may be the key receptor for butyrate therapy.
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