Sulfate-reducing bacteria Desulfovibrio fairfieldensis is an opportunistic pathogen that widely exists in the human intestine and can cause severe infectious diseases. However, the mechanisms contributing to its pathogenesis remain of great interest. In this study, we aim to investigate the outer membrane vesicles (OMVs) secreted by D. fairfieldensis and their pathogenic effect. The OMVs separated by ultracentrifugation were spherical and displayed a characteristic bilayer lipid structure observed by transmission electron microscopy, with an average hydrodynamic diameter of 75 nm measurement using the particle size analyzer. We identified 1496 and 916 proteins from D. fairfieldensis and its OMVs using label-free non-target quantitative proteomics, respectively. The 560 co-expressed proteins could participate in bacterial life activities by function prediction. The translocation protein TolB, which participates in OMVs biogenesis and transporting toxins was highly expressed in OMVs. The OMVs inhibited the expression of tight junction proteins OCCLUDIN and ZO-1 in human colonic epithelial cells (Caco-2). The OMVs decreased the cell viability of monocyte macrophages (THP-1-Mφ) and activated various inflammatory factors secretion, including interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), and many interleukins. Further, we found the OMVs induced the expression of cleaved-gasdermin D, caspase-1, and c-IL-1β and caused pyroptosis in THP-1-Mφ cells. Taken together, these data reveal that the D. fairfieldensis OMVs can damage the intestinal epithelial barrier and activate intrinsic inflammation.

Juice fermented with lactic acid bacteria (LAB) has received attention due to its health benefits, such as antioxidant and anti-inflammatory. Previous research on LAB-fermented goji juice mainly focused on exploring the changes in the metabolite profile and antioxidant activity in vitro, whereas the liver protection properties of LAB-fermented goji juice in vivo are still unknown. This study aimed to investigate the effects of Lacticaseibacillus paracasei E10-fermented goji juice (E10F), Lactiplantibacillus plantarum M-fermented goji juice (MF), Lacticaseibacillus rhamnosus LGG-fermented goji juice (LGGF) on preventing acute alcoholic liver injury with physiology, gut microbial, and metabolic profiles in mice. Compared with goji juice, E10F, MF, and LGGF enhanced the protective effect against liver injury by reducing serum alanine transaminase (ALT) levels, improving the hepatic glutathione (GSH) antioxidant system, and attenuating inflammation by decreasing the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β. Furthermore, E10F, MF, and LGGF increased intestinal integrity, restructured the gut microbiota including Bacteroides and Lactobacillus, and altered gut microbial metabolites including kyotorphin, indolelactic acid, and N-methylserotonin. Pretreatment of different LAB-fermented goji juice in mice showed significant differences in gut microbiota and metabolism. The correlation analysis demonstrated that the increase of Lactobacillus, indolelactic acid, and N-methylserotonin by E10F, MF, and LGGF was positively correlated with reduced inflammation and improved liver and gut function. Taken together, E10F, MF, and LGGF all have the potential to be converted into dietary interventions to combat acute alcoholic liver injury. It provided a reference for the study of the hepatoprotective effect of LAB-fermented goji juice.

A high-methionine diet led to increased LPS-TLR4 signaling and reduced the content of anti-inflammatory bioactive lipids, which damaged the gut barrier and allowed the translocation of bacterial products to the liver and induced hepatic steatosis.

Desulfovibrio (DSV), sulfate-reducing gut bacteria that generate hydrogen sulfide (H₂S), can impact host health through diverse mechanisms including bile acid (BA) metabolism. Although intestinal overgrowth of DSV expands the BA pool and promotes liver injury, its causal role in hepatic pathophysiology remains incompletely defined. Here, by employing complementary interventions of cholic acid (CA) supplementation and the BA sequestrant cholestyramine in mouse models, we show that DSV-driven liver injury is mediated by aberrant BA metabolism coupled with gut microbial remodeling. CA alone induced overt hepatic damage, whereas supplemental DSV did not further exacerbate injury caused by excessive CA. Intervention with the BA sequestrant cholestyramine markedly attenuated DSV-elicited hepatic inflammatory and histological alterations, which were associated with an upregulation of the intestinal BAs pool. Hepatic expression of BAs synthetic genes Cyp7a1 and Cyp8b1 verified a negative-feedback regulation of BA metabolism upon treatments. 16S rRNA gene sequencing revealed that CA, DSV, and the cholestyramine all significantly influenced the gut microbiota. CA reduced microbial richness and drove community separation, while DSV intervention under high BA conditions enriched specific biomarkers including Eubacterium ventriosum and Enterorhabdus. Notably, the administration of cholestyramine attenuated these DSV-associated microbial shifts and further reduced overall species richness, confirming the integral role of BA dynamics in shaping the gut microbial community. Collectively, our research reveals the intricate link between DSV, BAs, and gut microbiota in liver injury, and suggests that modulation of BAs may hold therapeutic potential for DSV-associated liver hepatic conditions.

Gut-liver axis has been a study focus for liver diseases. Diet is a key player in influencing the gut microbiota. However, the effect of different dietary patterns on gut microbiota and liver functions remains unclear. Here, we used mouse standard chow and purified diet to mimic two common human dietary patterns: healthy grain and planted-based diet and Western style diet, respectively and explored their impacts on the gut microbiota and liver. Gut microbiota experienced a great shift with notable increase in Desulfovibrio , gut bile acid (BA) concentration elevated significantly, and liver inflammation was observed in mice fed with the purified diet. Liver inflammation due to translocation of toxic lipopolysaccharides (LPS) and hydrophobic BAs from the damaged gut barrier was also observed in mice fed with the chow diet after receiving Desulfovibrio desulfuricans ATCC 29577 (DSV). Restricted intake of sulfur-containing amino acids reversed the liver injury due to excess Desulfovibrio through lowering the gut BA concentration and enhancing the hepatic antioxidant and detoxifying ability. Ex vivo fermentation of human fecal microbiota with primary BAs also demonstrated that DSV enhanced production of secondary BAs. Germ-free mice had higher concentration of both conjugated and unconjugated primary BAs in their gut after receiving DSV.