Proteomic antibacterial characterization of flavonoid xanthohumol and probiotic Clostridium butyricum on pathogenic Clostridioides difficile
文献类型：期刊论文
| 作者 | Wei, Shenkun3,4; Li, Guorong3; Yang, Qiong3; Zhu, Xinping3,4; Liang, Junjie3,4; Liu, Mengyi3,4; Chen, Zijian1; Liu, Xia3; Xu, Jun-Yu2,3,4; Chen, Wei1 |
| 刊名 | CHINESE MEDICINE
 |
| 出版日期 | 2026-02-03 |
| 卷号 | 21期号:1页码:21 |
| 关键词 | |
| ISSN号 | 1749-8546 |
| DOI | 10.1186/s13020-026-01343-x |
| 英文摘要 | BackgroundThe 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 difficile effects remain inadequately characterized.MethodsIn this study, we established a dextran sulfate sodium-induced inflammatory model using Caco-2 intestinal epithelial cells. The protective effects of xanthohumol against Clostridioides difficile infection superimposed on colitis were evaluated through cell viability assays, analysis of inflammatory signaling pathways, and proteomic profiling. Subsequent in vitro assays and proteomic analyses were conducted to assess the influence of xanthohumol and Clostridium butyricum supernatant on Clostridioides difficile. Furthermore, tandem mass tag-based post-translational modification proteomics was employed to elucidate the underlying molecular mechanisms and key pathways. Finally, critical metabolic enzyme activity assays were performed to validate the regulatory roles of these pathways.ResultsXanthohumol significantly alleviated C. difficile-induced damage in Caco-2 cells, enhanced cell viability, and suppressed the activation of inflammatory signaling pathways. In vitro experiments demonstrated that both xanthohumol and C. butyricum supernatant reduced bacterial colonization, inhibited growth, and attenuated toxin production. Proteomic analyses revealed substantial alterations in the proteome of C. difficile in response to each treatment. Post-translational modification proteomics further indicated that both treatments modulate lysine acetylation levels, influencing glycolysis pathways and ultimately diminishing the pathogen's virulence. Furthermore, mass spectrometry identified a specific lysine acetylation at the K280 site of fructose-1,6-bisphosphate aldolase, a key enzyme in glycolysis. Functional validation via site-directed mutagenesis confirmed the essential role of this acetylation in regulating the catalytic activity of fructose-1,6-bisphosphate aldolase.ConclusionsOur study demonstrates that xanthohumol and Clostridium butyricum attenuate the pathogenicity of Clostridioides difficile through modulation of lysine acetylation and disruption of glycolysis metabolism. These findings highlight their potential as promising therapeutic strategies for treating Clostridioides difficile infection. |
| WOS关键词 | GUT MICROBIOTA ; BUTYRATE |
| 资助项目 | National Health Commission Pharmaceutical Health Science and Technology Development Research Center of innovative drug post-marketing clinical research project[WKZX2024CX104301] ; Guangdong High-level Innovative Research Institute, China[Grant No.:2021B0909050003] ; Wenzhou Science and Technology Project[Y20220186] ; Discipline Cluster of Oncology, Wenzhou Medical University, China[No. z1-2023003] ; National Natural Science Foundation of China[32322048] ; Youth Innovation Promotion Association[CAS2021276] ; Shanghai Rising-Star Program[22QA1411100] ; Zhongshan Science and Technology Bureau[CXTD2024006] ; Sanofi scholarship program, Guangdong High-level New R&D Institute, China[Grant No.:2019B090904008] ; Innovative research team of high-level local universities in Shanghai[SHSMU-ZDCX20212700] ; Strategic Priority Research Program of the Chinese Academy of Sciences[Grant No. XDB1360000] ; Zhejiang Province Medical and health science and Technology project[2024KY141] ; Clinical and basic research project of Beijing Kangmeng Charity Foundation Medical Research and Development Fund[CB23005] ; Young Elite Scientists Sponsorship Program by CAST[2022QNRC001] ; National Key Research and Development Program of China[No. 2021YFA0804700] |
| WOS研究方向 | Integrative & Complementary Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001679433700002 |
| 出版者 | BMC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322737]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Liu, Xia; Xu, Jun-Yu; Chen, Wei |
| 作者单位 | 1.Wenzhou Med Univ, Affiliated Hosp 1, Dept Urol, Wenzhou, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Guangdong, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wei, Shenkun,Li, Guorong,Yang, Qiong,et al. Proteomic antibacterial characterization of flavonoid xanthohumol and probiotic Clostridium butyricum on pathogenic Clostridioides difficile[J]. CHINESE MEDICINE,2026,21(1):21. |
| APA | Wei, Shenkun.,Li, Guorong.,Yang, Qiong.,Zhu, Xinping.,Liang, Junjie.,...&Chen, Wei.(2026).Proteomic antibacterial characterization of flavonoid xanthohumol and probiotic Clostridium butyricum on pathogenic Clostridioides difficile.CHINESE MEDICINE,21(1),21. |
| MLA | Wei, Shenkun,et al."Proteomic antibacterial characterization of flavonoid xanthohumol and probiotic Clostridium butyricum on pathogenic Clostridioides difficile".CHINESE MEDICINE 21.1(2026):21. |
入库方式： OAI收割
来源：上海药物研究所
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