PHYTOMEDICINE
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2025
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IF 8.3
Zhe Song,Zhou Qiao,Jia Liu,Lingfei Han,Xi Chen,Yun Wang
Background The gut microbiota is firmly associated with the progression of ulcerative colitis (UC). Beneficial microbial metabolites, such as butyrate, exert vital roles in maintaining intestinal homeostasis. The Sea buckthorn berry is a traditional Chinese medicine homologous to food and medicine which is widely applied in the prevention and treatment of UC in clinic practice. Recent studies have exhibited the potential function of Sea buckthorn on regulating the gut microbiota, however, the mechanism underlying its anti-colitis effects and the key gut microbes mediating its efficacy are still unclear. Purpose This study is intended to explore the pharmacological mechanism of the efficacy of Sea buckthorn berries extract (SBE) in alleviating UC from the perspective of the gut microbial regulation. Methods The effect of SBE on UC was evaluated on dextran sulfate sodium (DSS)-induced murine model by assessing the body weight change, colon length, disease activity index (DAI), histopathological staining and the transcriptional expression of genes associated with inflammation and mucosal integrity. The dependence of the gut microbiota in the therapeutical effects of SBE on UC was confirmed by pseudo-germ-free mice and the co-housing experiment. The differential gut microbes altered by SBE were discovered by 16S rRNA sequencing and qPCR. The levels of short chain fatty acids (SCFAs) in bacterial medium and colonic contents were determined by GC–MS/MS. Bacterial colonization was conducted to estimate the effects of the bacteria on UC and to verify the involvement of the functional bacteria in the efficacy of SBE. A butyrate receptor G protein-coupled receptor (GPR)109A antagonist mepenzolate bromide (MPN) was used to validate the important role of butyrate and GPR109A in the anti-colitis effects of SBE and functional bacteria on UC. Two-way ANOVA was employed for multiple curve comparison and One-way ANOVA and Brown-Forsythe ANOVA test were used for multiple group comparison. Statistical significance was defined as p < 0.05 . Results SBE treatment significantly alleviated DSS-induced UC and its therapeutical effects was impaired in pseudo-germ-free mice. Moreover, the co-housing experiment exhibited that SBE-altered microbiota could effectively ameliorate UC. Further research demonstrated that Faecalibaculum rodentium was obviously increased by SBE and could be transferable by co-housing. Moreover, butyrate, a product of F. rodentium , dramatically decreased in UC mice while could be recovered by SBE administration. Abolishment of F. rodentium using vancomycin deprived the efficacy of SBE, but this could be reversed by recolonization of F. rodentium . Finally, blockage of the butyrate's receptor GPR109A weakened the effects of F. rodentium , indicating the indispensability of butyrate and GPR109A in the anti-colitis effects of F. rodentium . Conclusion SBE has potent therapeutical efficacy on UC including relieving inflammation and enhancing intestinal epithelial integrity, which is mediated by the gut F. rodentium -regulated butyrate−GPR109A axis.
研究领域:
微生物学
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药理学
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消化系统疾病
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2025
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IF 14.1
Hanyong Zhu,Hui Guo,Na Sun,Rui Xiao,Binbin Ji,Ruihan Jiang,Fuxing Dong,Chen Yao,Xuerong Wang,Rongqing Li,Jie Zhao,Xueqin Li,Shengzhe Gong,Yongqin Qin,Xin Chen,Yuchen Pan,Takayuki Ikezoe,Jing Yang
The gut microbiota is key to mitigating ionizing radiation (IR)–induced injuries; however, the specific species involved in and the molecular mechanisms remain elusive. Mitochondrial dynamics affect gut microbiota diversity. To identify the specific species involved in the radioprotective effect, we performed mitochondrial proteomic profiling of mouse intestinal epithelial cells and identified the accumulation of signal transducer and activator of transcription 3 (STAT3). Using mitochondrial STAT3 knock-in mice, we observed the abundance of the probiotic Faecalibaculum rodentium and its metabolite butyrate decreased in parallel with increased sensitivity to IR. Supplementation with Faecalibaculum rodentium or butyrate attenuated IR-induced intestinal barrier dysfunction, enhanced hematopoietic recovery, and prolonged survival. Butyrate is found to exert dual protective effects: It increases tight junction proteins, such as zonula occludens-1 (ZO-1) and occludin, and the defense factor levels to reinforce intestinal integrity. Furthermore, it sustains extracellular regulated protein kinases (ERK)-mediated pyruvate kinase isozyme type M2 (PKM2) nuclear localization, thereby attenuating p53-dependent apoptotic signaling in hematopoietic stem cells and ultimately prolonging mouse survival. These findings indicate that Faecalibaculum rodentium -derived butyrate confers radioprotection by maintaining the intestinal barrier and hematopoietic regeneration, suggesting a promising microbiota-directed therapeutic strategy against radiation-induced injury.
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2023
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IF 9.8
Xuyang Chai,Luyao Wen,Yuanyuan Song,Xiaochong He,Jingxian Yue,Jianlin Wu,Xin Chen,Zongwei Cai,Zenghua Qi
Phthalate esters (PAEs) are one of the significant classes of emerging contaminants that are increasingly detected in environmental and human samples. Nevertheless, the current toxicity studies rarely report how PAEs affect the cardiovascular system, especially in obese individuals. In this study, diet-induced obese mice and corresponding normal mice were exposed to di(2-ethylhexyl) phthalate (DEHP) by oral gavage at environmentally relevant concentrations and key characteristics of cardiovascular risk were examined. The 16S rRNA and high-resolution mass spectrometry were used to investigate the alterations in the gut microbial profile and metabolic homeostasis. The results indicated that the cardiovascular system of fat individuals was more susceptible to DEHP exposure than mice in the lean group. 16S rRNA-based profiling and correlation analysis collectively suggested DEHP-induced gut microbial remodeling in fed a high-fat diet mice, represented by the abundance of the genus Faecalibaculum . Using metagenomic approaches, Faecalibaculum rodentium was identified as the top-ranked candidate bacterium. Additionally, metabolomics data revealed that DEHP exposure altered the gut metabolic homeostasis of arachidonic acid (AA), which is associated with adverse cardiovascular events. Finally, cultures of Faecalibaculum rodentium were treated with AA in vitro to verify the role of Faecalibaculum rodentium in altering AA metabolism. Our findings provide novel insights into DEHP exposure induced cardiovascular damage in obese individuals and suggest that AA could be used as a potential modulator of gut microbiota to prevent related diseases.
研究领域:
毒理学
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微生物学
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心血管科学
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环境健康
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代谢组学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Cheng-Qiang Wang,Zou Su,Chun-Guang Dai,Jia-Le Song,Bo Qian
2,2′,4,4′-tetrabromodiphenyl ether (BDE47) is a foodborne environmental risk factor for depression, but the pathogenic mechanism has yet to be fully characterized. In this study, we clarified the effect of BDE47 on depression in mice. The abnormal regulation of the microbiome-gut-brain axis is evidenced closely associated with the development of depression. Using RNA sequencing, metabolomics, and 16s rDNA amplicon sequencing, the role of the microbiome-gut-brain axis in depression was also explored. The results showed that BDE47 exposure increased depression-like behaviors in mice but inhibited the learning memory ability of mice. The RNA sequencing analysis showed that BDE47 exposure disrupted dopamine transmission in the brain of mice. Meanwhile, BDE47 exposure reduced protein levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT), activated astrocytes and microglia cells, and increased protein levels of NLRP3, IL-6, IL-1β, and TNF-α in the brain of mice. The 16 s rDNA sequencing analysis showed that BDE47 exposure disrupted microbiota communities in the intestinal contents of mice, and faecalibaculum was the most increased genus. Moreover, BDE47 exposure increased the levels of IL-6, IL-1β, and TNF-α in the colon and serum of mice but decreased the levels of tight junction protein ZO-1 and Occludin in the colon and brain of mice. In addition, the metabolomic analysis revealed that BDE47 exposure induced metabolic disorders of arachidonic acid and neurotransmitter 2-Arachidonoyl glycerol (2-AG) was one of the most decreased metabolites. Correlation analysis further revealed gut microbial dysbiosis, particularly faecalibaculum , is associated with altered gut metabolites and serum cytokines in response to BDE47 exposure. Our results suggest that BDE47 might induce depression-like behavior in mice through gut microbial dysbiosis. The mechanism might be associated with the inhibited 2-AG signaling and increased inflammatory signaling in the gut-brain axis.
研究领域:
神经科学
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药理学
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分子生物学
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微生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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