Gut Microbes
·
2023
·
IF 12.2
Hui Xu,Haidan Luo,Jiayu Zhang,Kai Li,Mong-Hong Lee
Probiotic roles of Clostridium butyricum (C.B) are involved in regulating disease and cancers, yet the mechanistic basis for these regulatory roles remains largely unknown. Here, we demonstrate that C.B reprograms the proliferation, migration, stemness, and tumor growth in CRC by regulating pivotal signal molecules including MYC. Destabilization of MYC by C.B supplementation suppresses cancer cell proliferation/metastasis, sensitizes 5-FU treatment, and boosts responsiveness of anti-PD1 therapy. MYC is a transcriptional regulator of Thymidylate synthase (TYMS), a key target of the 5-FU. Also MYC is known to impact on PD-1 expression. Mechanistically, C.B treatment of CRC cells results in MYC degradation by enhancing proteasome-mediated ubiquitination, thereby mitigating MYC-mediated 5-FU resistance and boosting anti-PD1 immunotherapeutic efficacy. Together, our findings uncover previously unappreciated links between C.B and CRC cell signaling, providing insight into the tumorigenesis modulating mechanisms of C.B in boosting chemo/immune therapies.
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-11
·
IF 5.228
Dan Jiang,Fang Zhen,Chin Siew-xian,Tian Xiao-fei,Su Tong-chao
Biohydrogen production has received widespread attention from researchers in industry and academic fields. Response surface methodology (RSM) was applied to evaluate the effects of several key variables in anaerobic fermentation of glucose with Clostridium butyrium and achieved the highest production rate and yield of hydrogen. Highest H 2 yield of 2.02 mol H 2 /mol-glucose was achieved from 24 h bottle fermentation of glucose at 35 °C, while the composition of medium was (g/L): 15.66 glucose, 6.04 yeast extract, 4 tryptone, 3 K 2 HPO 4 , 3 KH 2 PO 4 , 0.05 L-cysteine, 0.05 MgSO 4 ·7H 2 O, 0.1 MnSO 4 ·H 2 O and 0.3 FeSO 4 ·7H 2 O, which was very different from that for cell growth. Sugarcane bagasse and Jatropha hulls were selected as typical tropical biomass wastes to produce sugars via a two-step acid hydrolysis for hydrogen production. Under the optimized fermentation conditions, H 2 yield (mol H 2 /mol-total reducing sugar) was 2.15 for glucose, 2.06 for bagasse hydrolysate and 1.95 for Jatropha hull hydrolysate in a 3L fermenter for 24 h at 35 °C, with H 2 purity of 49.7–64.34%. The results provide useful information and basic data for practical use of tropical plant wastes to produce hydrogen.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Qinglian Hu,Xiangchi Xu,Jing Feng,Jiyue Hu,Chaozhi Wei,Jintao Cheng,Yue Chen,Yuanxiang Jin
A collaborative intervention strategy based on probiotics represents a promising therapeutic approach against inflammatory bowel disease (IBD). However, enhancing probiotic efficacy within the IBD microenvironment while minimizing side effects remains a critical challenge. Polygonatum polysaccharide (PP), a natural plant-derived bioactive polymer, has attracted significant attention due to its ability to regulate oxidative and inflammatory stress with a favorable safety profile. Herein, PP was incorporated into calcium-alginate microgels (Mgel), resulting in enhanced mechanical strength and thermal stability. Compared to conventional calcium-alginate microgels, the PP-loaded microgels exhibited improved performance in oral delivery. In addition, PP functions as a promising microenvironmental modulator, exhibiting broad-spectrum antioxidant, anti-inflammatory, and prebiotic properties. The microgel system provides a versatile platform for probiotic oral delivery, contributing to the reshaping of the IBD microenvironment by enhancing the efficacy of Clostridium butyricum JHP6 and increasing beneficial metabolite levels in colitis. Collectively, naturally derived polysaccharide-based microspheres encapsulating probiotics offer an effective strategy to modulate the IBD microenvironment and enhance probiotic efficacy, thereby representing a collaborative intervention approach for IBD.
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 5.9
Qingyu Zhang,Kailun He,Mohd Shafiq Aazmi,Mohd Fakharul Zaman Raja Yahya
Background: Extracellular vesicles (EVs) of probiotics are an important pathway for probiotics to exert probiotic effects. EVs of Clostridium butyricum (C. butyricum) has great potential in immunotherapy. The aim of this study is to investigate the regulatory effect of C. butyricum EVs on the pyroptosis-related gene network in LPS-stimulated macrophages and explore its potential molecular mechanisms.Methods: Differential centrifugation was used to isolate C. butyricum EVs, and EVs were characterized by transmission electron microscopy, NTA, and ZETA potential. PI staining was employed to confirm the stimulatory effect of LPS on RAW264.7 cells. Transcriptome sequencing and qPCR were performed to validate the regulatory effects of EVs on pyroptosis-related genes (PRGs) in LPS-stimulated RAW264.7 cells.Results: C. butyricum EVs exhibited a bilayer membrane structure with a median particle size of 144.4 ± 85.7 nm and a ZETA potential of -37.56 ± 1.08 mV. PI staining showed that LPS induced cell death in RAW264.7 macrophages, while EV treatment significantly affected the expression of pyroptosis-related genes IL-18 and IL-33 (q < 0.05). Transcriptome analysis revealed that C. butyricum EVs induce inflammation and cytokine secretion in RAW264.7 macrophages through the JAK-STAT signaling pathway and Cytokine receptor interaction. EVs pretreatment (10/20 μg/mL) regulated the expression of 14 PRGs in a concentration-related manner, including significant upregulation of IL-6 and P2rx7 (q < 0.01) and inhibition of ZBP1 and Tnf (q < 0.05). The gene interaction network showed a positive correlation (r=0.82) between IL-6 and P2rx7, and a negative correlation (r=-0.75) between ZBP1 and P2rx7.Conclusion: C. butyricum EVs remodel the pyroptosis-related regulatory network by modulating key genes such as IL-6, P2rx7, and ZBP1, suggesting their potential role in fine-tuning LPS-induced inflammatory responses in macrophages.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2025
·
IF 6.9
Qinchao Ding,Feiwei Cao,Shanglei Lai,Jundi Yu,Yibo Zeng,Teresa G. Valencak,Shuo Zhang,Xiu Zhang,Xiaobing Dou,Songtao Li,Daxi Ren
Alcohol-associated liver disease (ALD) has become a serious public health issue worldwide. This study was conducted to investigate the protective role of Lactobacillus helveticus ZJUIDS12 (Z12) on ALD. Z12 (10 9 CFU/day) significantly reversed alcohol-induced liver injury, hepatic steatosis, oxidative stress, and inflammation by restoring lipid metabolism and gut barrier integrity. Z12's effects, abolished in antibiotic-treated mice, involve gut microbiota, notably Clostridium sensu stricto 1, linked to Reg3γ upregulation. Clostridium butyricum (a representative strain of Clostridium sensu stricto 1) or butyric acid replicated Z12's benefits, which were absent in Reg3γ −/− mice. Further studies revealed that the heat-inactivated postbiotics of Z12 and its secreted exopolysaccharides still significantly alleviated ALD, similar to the effects of the live Z12. Our present study suggests that Z12 probiotics and their postbiotics ameliorate alcohol-induced hepatic steatosis and liver injury in mice by enhancing butyrate production via C. butyricum , mediated through the Reg3γ pathway. These findings support the therapeutic potential of probiotic and postbiotic interventions for ALD.
✓ 已验证
产品关联
DOI
高影响因子
CANCER LETTERS
·
2019
·
IF 6.508
Danfeng Chen,Duochen Jin,Shumin Huang,Jingyi Wu,Mengque Xu,Tianyu Liu,Wenxiao Dong,Xiang Liu,Sinan Wang,Weilong Zhong,Yi Liu,Ruihuan Jiang,Meiyu Piao,Bangmao Wang,Hailong Cao
Gut microbiota dysbiosis is closely involved in intestinal carcinogenesis. A marked reduction in butyrate-producing bacteria has been observed in patients with colorectal cancer (CRC); nevertheless, the potential benefit of butyrate-producing bacteria against intestinal tumor development has not been fully investigated. We found that Clostridium butyricum ( C. butyricum , one of the commonly used butyrate-producing bacteria in clinical settings) significantly inhibited high-fat diet (HFD)-induced intestinal tumor development in Apc min/+ mice. Moreover, intestinal tumor cells treated with C. butyricum exhibited decreased proliferation and increased apoptosis . Additionally, C. butyricum suppressed the Wnt/β-catenin signaling pathway and modulated the gut microbiota composition, as demonstrated by decreases in some pathogenic bacteria and bile acid (BA)-biotransforming bacteria and increases in some beneficial bacteria, including short-chain fatty acid (SCFA)-producing bacteria. Accordingly, C. butyricum decreased the fecal secondary BA contents, increased the cecal SCFA quantities, and activated G-protein coupled receptors (GPRs), such as GPR43 and GPR109A. The anti-proliferative effect of C. butyricum was blunted by GPR43 gene silencing using small interfering RNA (siRNA). The analysis of clinical specimens revealed that the expression of GPR43 and GPR109A gradually decreased from human normal colonic tissue to adenoma to carcinoma. Together, our results show that C. butyricum can inhibit intestinal tumor development by modulating Wnt signaling and gut microbiota and thus suggest the potential efficacy of butyrate-producing bacteria against CRC.
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yongqiang He,Ruxiang Ma,Niu Feng,Yiping Chen
Due to the significant health risks posed by pathogenic bacteria, there is an urgent need to develop multiplex, sensitive detection methods for them. Here, we developed a highly sensitive fluorescent sensor for the detection of pathogens by leveraging the powerful programmability of Clostridium butyricum Argonaute ( Cb Ago)-assisted exponential isothermal amplification reaction (EXPAR). This system combined Cb Ago, which locally cleaved extracted genomic DNA to produce single-stranded DNA (ssDNA), with EXPAR, which induced the amplification of large DNAzyme fragments by the ssDNA. Each DNAzyme fragment cleaved a specific reporter to generate a fluorescent signal for quantification of pathogenic bacteria. The EXPAR templates were carefully designed to ensure sufficient specificity for multiplex detection. The assay demonstrated superior analytical performance, with a limit of detection of as low as 4 CFU mL −1 and a linear range of 10–10 7 CFU mL −1 . This method represents the integration of Cb Ago-mediated genome editing and EXPAR high-efficiency amplification, yielding a customizable nucleic acid detection tool with broad applications in pathogen detection
✓ 已验证
产品关联
DOI
高影响因子
Nano Today
·
2025
·
IF 10.9
Shengke Zhao,Yunjian Yu,Youtao Xin,Hegang Lu,Xiaohui Li,Shuyu Wang,Feihe Ma,Hui Gao
The gut microbiota plays a crucial role in host immune modulation and maintaining homeostasis. An abnormal increase in certain pathogens such as Fusobacterium nucleatum ( Fn ) can break homeostasis and drive the progression of various intestinal diseases. Supplementing probiotics can partially counteract these effects without flora disturbance. However, broad-spectrum antibacterial treatments are not compatible with probiotic therapy in a therapeutic system due to their non-selective damage on both probiotics and the overall gut microbiota. Herein, we screen and identify lauric acid (LA)-derived lipid, S12, from a combinatorial library of 12 chemically diverse lipids for its selective antibacterial activity against Fn over probiotic Clostridium butyricum ( Cb ). This lipid is then utilized as a single-cell carrier to orally deliver Cb ( Cb @S12) for enhanced treatment of Fn -associated intestinal diseases. The surface arming of S12 effectively protects Cb from simulated gastric and intestinal fluids, thus significantly prolonging its intestinal retention in mice. Oral administration of Cb @S12 has demonstrated impressive therapeutic outcomes against Fn -aggravated inflammatory bowel disease and orthotopic colorectal cancer by selectively eliminating Fn while preserving the probiotic activity of Cb . This study introduces a robust approach using selectively antibacterial lipids for probiotic encapsulation, offering an antibiotic-free “probiotic-antagonistic” combination therapeutic strategy for intestinal diseases.
✓ 已验证
产品关联
DOI
高影响因子
BEHAVIOURAL BRAIN RESEARCH
·
2026
·
IF 2.9
Shufen Wu,Jingyuan Zhang,Yiru Yin,Enhui Li,Yu Zhang,Jianguo Li,Xiaorong Yang,Xin Zhao,Xiang Zan,Zhengyin Guo,Zihan Feng,Jianing Xie,Chenlong Cui,Lijun Zhao,Ce Zhang
Brain aging primarily manifests as cognitive decline. Spermidine (SPD) is known to ameliorate age-related cognitive decline, and the gut microbiota is an important source of SPD. Clostridium butyricum ( C. butyricum ), a probiotic, can alleviate cognitive decline in individuals with various neurodegenerative diseases, and C. butyricum might generate SPD. However, the role of C. butyricum in natural brain aging and the efficacy of C. butyricum and the metabolite SPD in ameliorating age-related cognitive decline remain unclear. Here, we investigated the effects of C. butyricum and its metabolite SPD on cognitive decline during natural brain aging and the mechanisms underlying these effects. Aged rats (aged 17 months, n = 12 per group) were randomly divided into normal saline (NS), C. butyricum (1 ×10 8 ∼10 9 CFU/ml, by gavage for two months) and SPD (6.5 mg/kg/d, by gavage for one month) groups. Compared with the NS group, the C. butyricum and SPD groups presented improved spatial reference and recognition memory, reduced aging marker levels by immunohistochemical staining, improved synaptic plasticity-related tissue structure by transmission electron microscopy and Golgi staining, and increased level of synaptophysin and BDNF by immunofluorescence staining and western blotting in the brain. Furthermore, treatment with C. butyricum and SPD enhanced intestinal barrier function and decreased serum proinflammatory factor levels and brain tissue damage due to oxidative stress. There were no significant differences in relevant indicators between the C. butyricum and SPD groups. In conclusion, C. butyricum and its metabolite SPD may delay the cognitive decline caused by normal brain aging by reducing oxidative stress and inflammation.
✓ 已验证
DOI
PubMed
高影响因子
ACS Synthetic Biology
·
2022
·
IF 5.249
Amreesh Parvez,Yuvaraj Ravikumar,Renu Bisht,Junhua Yun,Yang Wang,Sabapathy Poorna Chandrika,Hossain M. Zabed,Xianghui Qi
Biosynthesis of 1,3-propanediol (1,3-PD) by 1,3-propanediol oxidoreductase (PDOR) is often limited by the stability issues. To address this issue, the goal of the present study was to engineer the Clostridium butyricum PDOR dimeric interface. The interface exists between the chains and plays a role in the synthesis of 1,3-PD, which is hindered by the increased temperature and pH. Herein, we engineered PDOR by HotSpot Wizard 3.0 and molecular dynamics simulations, improving its thermal stability, pH tolerance, and catalytic properties with respect to the wild-type PDOR activity at 37 °C. Compared to the activity of the wild-type PDOR, the N298C mutant showed 0.5-fold greater activity at pH 8.0, while the P299E mutant showed significantly increased activity of over five fold at pH 4.0. Further structural comparisons between the wild-type and P299E mutant revealed that the extraordinary stability of the P299E mutant could be due to the formation of additional hydrogen bonds and salt bridges. The N298C mutant also exhibits thermal stability at a broad range of temperature at pH 8 with respect to wild-type PDOR and other mutants. The molecular dynamics simulations revealed that stability profiles of P299E mutants at pH 4.0 are attributed to identical root mean square deviation values and stable conformations in the motif region present in the dimer interface of the enzyme. These findings suggest that the dimer interface motifs are essential for the compactness and stability of the PDOR enzyme; therefore, engineering the PDOR using a structure-guided approach could aid in improving its activity and stability under various physiological conditions (pH and temperature).
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Yongzhen Dong,Aoting Gu,Chunling Li,Huihui Wang,Yang Zhou,Zhixiong Pi,Chengjia Jiang,Yiping Chen
A CbAgo-CRISPR/Cas12a-powered cascade amplification sensing strategy was proposed. • It combined CbAgo's precise cleavage with the Cas12a's robust trans-cleavage activity. • An amplified fluorescent biosensor was developed for detecting Salmonella Typhimurium . • The proposed biosensor demonstrated comparable analytical performance to qPCR assay. Sensitive and accurate detection of foodborne pathogens constitutes a critical imperative for safeguarding food safety. Herein, we proposed a Clostridium butyricum argonaute (Cb A go)-CRISPR/ C as12a-powered synergistic amplification strategy and developed a DNA amplification-free f luorescent ( ACF ) biosensor for ultrasensitive detection of Salmonella Typhimurium . In this biosensor, magnetic beads-phage conjugates enabled the selective capture of viable Salmonella Typhimurium , followed by rapid DNA extraction within 5 min using commercial lysis buffers. A synergistic signal amplification strategy was designed for efficient biosensing by utilizing the primary cleavage product (tDNA) of the CbAgo system as a molecular bridge to integrate CbAgo and Cas12a systems. Specifically, CbAgo performed primary cleavage of target DNA to generate tDNA fragments. These tDNA subsequently activated the CRISPR/Cas12a system, initiating its trans-cleavage activity to degrade fluorescent reporter probes for quantitative analysis. This tDNA-mediated integration synergizes CbAgo's precision cleavage capability with Cas12a's efficient trans-cleavage activity, enabling exponential amplification. Under optimized conditions, the ACF biosensor exhibited a linear detection range of 10 2 –10 7 CFU/mL and a detection limit of 24.8 CFU/mL for Salmonella Typhimurium without DNA amplification steps. Moreover, the ACF biosensor demonstrated comparable analytical performance to the qPCR assay and achieved satisfactory results in the detection of Salmonella Typhimurium in 20 food samples, highlighting its potential as an ultrasensitive tool for foodborne pathogen monitoring. Download: Download high-res image (107KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
Translational Oncology
·
2026
·
IF 4.9
Zhuo Chen,Meng-Lei Wang,Zhuo-Wen Zhang,Peng-Cheng Zhang,Qing-fang Yang,Yu-jing Weng,Jia-Long Shen,Wenxian Wang,Lan Shao
Background PD-1 blockade has become an important immunotherapeutic strategy, its clinical efficacy in non-small cell lung cancer (NSCLC) remains suboptimal. This study explores the effect and mechanism of sodium butyrate (NaB) and Clostridium butyricum ( C. butyricum ) combined with PD-1 inhibitors in NSCLC. Methods We established an NSCLC mouse model and evaluated tumor size, histopathology, apoptosis, cell proliferation, inflammatory factors, immune cell populations, and proteins of the HDAC1/ID2/IL-12R axis in the tumor, along with gut microbiome profiling. Results A combination of NaB or C. butyricum with PD-1 inhibitors significantly inhibited tumor growth and increased spleen and thymus indices. The combinations promoted tumor cell apoptosis, reduced the number of Ki67-positive proliferating cells, and increased IL-2, IL-6, IL-12, TNF-α, and IFN-γ levels in tumor tissues and serum. Additionally, the infiltration of CD4 + and CD8 + T cells in the tumor increased, while the Treg cells decreased. Importantly, the expressions of HDAC1 were markedly decreased, whereas ID2 and IL-12R levels increased in tumor tissues from NaB or C. butyricum with PD-1 inhibitor groups. Meanwhile, the combination of NaB or C. butyricum with PD‑1 inhibitors could alleviate the disturbance of gut microbiota by decreasing the Gordonibacter and increasing the WCHB1-32 . Significantly, the anti-CD8 antibody attenuated the inhibition of tumor growth conferred by NaB and PD‑1 inhibitors in vivo. Conclusions Collectively, NaB and C. butyricum enhanced the therapeutic action of PD‑1 inhibitors in murine models of NSCLC, possibly by modulating the HDAC1/ID2/IL-12R pathway, impacting intestinal microbiota and immune microenvironment.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）