New strain of Pediococcus pentosaceus alleviates ethanol-induced liver injury by modulating the gut microbiota and short-chain fatty acid metabolism

Abstract

BACKGROUND Intestinal dysbiosis has been shown to be associated with the pathogenesis of alcoholic liver disease (ALD), which includes changes in the microbiota composition and bacterial overgrowth, but an effective microbe-based therapy is lacking. Pediococcus pentosaceus ( P. pentosaceus ) CGMCC 7049 is a newly isolated strain of probiotic that has been shown to be resistant to ethanol and bile salts. However, further studies are needed to determine whether P. pentosaceus exerts a protective effect on ALD and to elucidate the potential mechanism. AIM To evaluate the protective effect of the probiotic P. pentosaceus on ethanol-induced liver injury in mice. METHODS A new ethanol-resistant strain of P. pentosaceus CGMCC 7049 was isolated from healthy adults in our laboratory. The chronic plus binge model of experimental ALD was established to evaluate the protective effects. Twenty-eight C57BL/6 mice were randomly divided into three groups: The control group received a pair-fed control diet and oral gavage with sterile phosphate buffered saline, the EtOH group received a ten-day Lieber-DeCarli diet containing 5% ethanol and oral gavage with phosphate buffered saline, and the P. pentosaceus group received a 5% ethanol Lieber-DeCarli diet but was treated with P. pentosaceus . One dose of isocaloric maltose dextrin or ethanol was administered by oral gavage on day 11, and the mice were sacrificed nine hours later. Blood and tissue samples (liver and gut) were harvested to evaluate gut barrier function and liver injury-related parameters. Fresh cecal contents were collected, gas chromatography–mass spectrometry was used to measure short-chain fatty acid (SCFA) concentrations, and the microbiota composition was analyzed using 16S rRNA gene sequencing. RESULTS The P. pentosaceus treatment improved ethanol-induced liver injury, with lower alanine aminotransferase, aspartate transaminase and triglyceride levels and decreased neutrophil infiltration. These changes were accompanied by decreased levels of endotoxin and inflammatory cytokines, including interleukin-5, tumor necrosis factor-α, granulocyte colony-stimulating factor, keratinocyte-derived protein chemokine, macrophage inflammatory protein-1α and monocyte chemoattractant protein-1. Ethanol feeding resulted in intestinal dysbiosis and gut barrier disruption, increased relative abundance of potentially pathogenic Escherichia and Staphylococcus , and the depletion of SCFA-producing bacteria, such as Prevotella, Faecalibacterium , and Clostridium . In contrast, P. pentosaceus administration increased the microbial divers...

Translational Approaches with Antioxidant Phytochemicals against Alcohol-Mediated Oxidative Stress, Gut Dysbiosis, Intestinal Barrier Dysfunction, and Fatty Liver Disease

“…Additionally, butyrate can restrain cytokine (TNFα and MCP-1) production following acute alcohol exposure, although it does not appear to ameliorate alcohol-induced steatosis [ 267 ]. Indirect benefits of SCFA supplementation might also be achieved through administration of Pediococcus pentosaceus , which increased the levels of the SCFAs possibly due to the partial recovery of bacterial genera, such as Clostridium, whose levels were decreased in the mouse model of chronic plus binge alcohol exposure and whose recovery could increase SCFA production, as suggested by the positive correlation found between Clostridium and butyric acid levels in this study [ 268 ]. Administration of other SCFAs or other beneficial microbial products may yield similar results to butyrate supplementation, such as administration of indole-3-propionic acid (IPA), an indole metabolite generated by the metabolism of tryptophan, which elevated gut tight junction proteins, thus preventing intestinal barrier dysfunction and liver damage in rats exposed to a Western-style HFD, possibly by the gut–liver axis [ 269 ].…”

Alcohol’s Impact on the Gut and Liver

“…Analysis of the faecal metabolome in humans with alcohol use disorders revealed a reduction in SCFAs, which is likely to be due in part to dysbiosis that negatively affects SCFA-producing bacteria such as Faecalibacterium [ 15 , 21 ]. Several murine models have reliably shown that supplementation with SCFAs in either the form of a high fibre diet, probiotic or dietary modification enhances gut epithelial integrity and reduces liver injury in alcoholic models, and work in this area is ongoing [ 22 , 23 , 24 ].…”

Gut Microbiota and Chemical-Induced Acute Liver Injury

“…Meanwhile, there have been reports on the intervention of the gut microbiota in acute alcoholic liver disease. The supplementation of Pediococcus pentosaceus CGMCC 7,049 improved the intestinal barrier function and reversed gut microbiota dysbiosis by reducing the level of circulating endotoxin and proinflammatory cytokines (Jiang et al, 2020 ).…”