Dataset Information

Proteomic Antibacterial Characterization of Flavonoid Xanthohumol and probiotic Clostridium butyricum on Pathogenic Clostridioides difficile

ABSTRACT: In this study, we evaluated the antimicrobial properties of XN and C. butyricum culture supernatant (CBs) against C. difficile, focusing on their ability to reduce C. difficile adhesion, inhibit growth, and restrict toxin production. Using a dextran sulfate sodium (DSS)-induced Caco-2 intestinal epithelial model, we demonstrated that XN alleviates C. difficile-induced epithelial barrier disruption and inhibits the activation of related inflammatory signaling pathways. Additionally, our research indicated that both XN and C. butyricum effectively prevent CDI-induced cellular damage and led to significant proteomic regulation in this pathogen. We then mapped the global acetylation landscape of C. difficile proteins response to these two conditions, revealing that lysine acetylation regulates pathogenicity by modulating glycolysis pathways and the activity of metabolic enzymes. These findings suggest that XN and CBs may represent promising therapeutic options for CDI, which serving as a valuable resource for investigating lysine acetylation in C. difficile metabolism and virulence.

ORGANISM(S): Clostridioides Difficile 70-100-2010 Clostridioides Difficile Atcc 9689 = Dsm 1296

SUBMITTER: Junyu Xu

PROVIDER: PXD069714 | iProX | Tue Oct 21 00:00:00 BST 2025

REPOSITORIES: iProX

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Proteomic antibacterial characterization of flavonoid xanthohumol and probiotic Clostridium butyricum on pathogenic Clostridioides difficile.

Wei Shenkun S Li Guorong G Yang Qiong Q Zhu Xinping X Liang Junjie J Liu Mengyi M Chen Zijian Z Liu Xia X Xu Jun-Yu JY Chen Wei W

Chinese medicine 20260203 1

<h4>Background</h4>The management of dysbiotic gut microbiota in Clostridioides difficile infection has attracted increasing scholarly attention. The development of therapeutic agents with low toxicity, derived from both the flavonoid xanthohumol and the short-chain fatty acid-producing probiotic Clostridium butyricum, holds considerable promise for combating Clostridioides difficile infection. Despite their therapeutic potential, the molecular mechanisms underlying the anti-Clostridioides diffi ...[more]

PMID: 41634763

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Project description:Objective: Enterococcus faecalis has been implicated in the development of colorectal cancer (CRC) in murine models through the microbiota-induced bystander effect (MIBE). This study aimed to investigate whether this commensal bacterium induces epigenetic alterations via MIBE. Methods: Murine macrophage RAW264.7 cells were treated with either superoxide-producing E. faecalis OG1RF or superoxide-deficient WY84. Conditioned medium (CM) was then collected and used to treat IEC-6 rat intestinal epithelial cells. Histone acetylation states and related signaling pathways were analyzed using immunoblotting, immunofluorescent staining, and chromatin immunoprecipitation sequencing (ChIP-seq). Results: CM derived from E. faecalis-infected macrophages significantly induced histone H3 acetylation at lysine 27 and 9 (H3K27ac/H3K9ac) in IEC-6 cells compared to controls. Furthermore, this CM inhibited histone deacetylases, which contributed to the increased in H3 acetylation. ChIP-seq analysis revealed widespread alterations in H3K27ac across the genome in cells treated with E. faecalis-infected macrophage-derived CM. Additionally, these changes were associated with aberrantly activated TGF-β signaling, leading to epithelial-mesenchymal transition (EMT). Targeted metabolomic analysis indicated that E. faecalis activated arachidonate lipoxygenase-12 (Alox12) in macrophages, resulting in the production of 12-hydroxyeicosatetraenoic acid (12-HETE), which induces H3 acetylation via the bystander effect (BSE). Conclusion: Infection with E. faecalis activates Alox12 in macrophages, leading to the production of 12-HETE that subsequently induces H3 acetylation through the BSE. This aberrant H3 acetylation alters gene expression associated with TGF-β signaling, promoting EMT. These findings elucidate the mechanisms by which commensal bacteria may initiate and promote CRC, potentially providing insights for the development of novel strategies for CRC prevention and treatment.

Dataset Information

Proteomic Antibacterial Characterization of Flavonoid Xanthohumol and probiotic Clostridium butyricum on Pathogenic Clostridioides difficile

Publications

Proteomic antibacterial characterization of flavonoid xanthohumol and probiotic Clostridium butyricum on pathogenic Clostridioides difficile.

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