PLoS One
·
2020
·Vol. 15
·期 10
·e0240920
·
IF 2.74
Li-Wei Gao,Hong-Tao Zhu,Cai-Yun Liu,Zhi-Xiang Lv,Xiao-Man Fan,Ye-Wang Zhang
As one of the most extensively studied glycosaminoglycan lyases, heparinase I has been used in producing low or ultra-low molecular weight heparin. Its’ important applications are to neutralize the heparin in human blood and analyze heparin structure in the clinic. However, the low productivity and activity of the enzyme have greatly hindered its applications. In this study, a novel Hep-I from Bacteroides cellulosilyticus (BcHep-I) was successfully cloned and heterologously expressed in E . coli BL21 (DE3) as a soluble protein. The molecular mass and isoelectric point (pI) of the enzyme are 44.42 kDa and 9.02, respectively. And the characterization of BcHep-I after purified with Ni-NTA affinity chromatography suggested that it is a mesophilic enzyme. BcHep-I can be activated by 1 mM Ca 2+ , Mg 2+ , and Mn 2+ , while severely inhibited by Zn 2+ , Co 2+ , and EDTA. The specific activity of the enzyme was 738.3 U·mg -1 which is the highest activity ever reported. The K m and V max were calculated as 0.17 mg·mL -1 and 740.58 U·mg -1 , respectively. Besides, the half-life of 300 min at 30°C showed BcHep-I has practical applications. Homology modeling and substrate docking revealed that Gln15, Lys74, Arg76, Lys104, Arg149, Gln208, Tyr336, Tyr342, and Lys338 were mainly involved in the substrate binding of Hep-I, and 11 hydrogen bonds were formed between heparin and the enzyme. These results indicated that BcHep-I with high activity has great potential applications in the industrial production of heparin, especially in the clinic to neutralize heparin.
研究领域:
生物化学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Suhang Guo,Yi Peng,Yan Lou,Lijuan Cao,Junqing Liu,Nengming Lin,Sheng Cai,Yu Kang,Su Zeng,Lushan Yu
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the world. The downregulation of farnesoid X receptor (FXR) is frequently founded in CRC patients. The current study found that the decreased expression of FXR in colorectal cancer leads to disorders of bile acids (BAs) metabolism. The altered BAs profile shaped distinct intestinal flora and positively regulated secretory immunoglobulin A (sIgA). The dual regulation of BAs and sIgA enhanced adhesion and biofilm formation of enterotoxigenic Bacteroides fragilis (ETBF), which has a colorectal tumorigenesis effect. The abundance of ETBF increased significantly in intestinal mucosa of colitis-associated cancer (CAC) mice, and finally promoted the development of colorectal cancer. This study suggests that downregulation of FXR in CRC results in BAs dysregulation, and BAs have strong effects on sIgA and gut flora. The elevated BAs concentration and altered gut microbiome are risk factors for CRC.
研究领域:
肿瘤学
·
胃肠病学
·
微生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Xiaojiang Wang,Yan Lu,Meixia Li,Xiao Xia,Can Jin,Kan Ding,Daofeng Chen
Commelina communis L., a functional food and herbal plant in Asia, has been used against obesity, diabetes, and infections for centuries. A growing body of studies has demonstrated that indigestible polysaccharides are significant in obesity management. However, the structures and bioactivities of homogeneous polysaccharides from C. communis remain unclear. This study presented the structural characterization, simulated digestion, and human gut Bacteroides proliferation promotion activity of a novel homogeneous polysaccharide (CCB-3) from C. communis . The results showed that CCB-3 was an arabinoglucuronoxylan, primarily composed of arabinose, galactose, xylose, glucuronic acid (GlcA), and 4- O -methyl GlcA with a molecular weight ( Mw ) of 58.8 kDa. Following a 6-hour exposure to simulated gastrointestinal fluid, the Mw of CCB-3 remained unchanged, revealing that CCB-3 was an indigestible polysaccharide. Notably, CCB-3 could promote the proliferation of B. thetaiotaomicron, B . ovatus , and B . cellulosilyticus and produce short-chain fatty acids (SCFAs) and 1,2-propanediol. These findings might shed light on the discovery of polysaccharide-based leading compounds from C. communis against obesity.
研究领域:
食品科学
·
微生物学
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植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Yu Biao,Lu Zheng,Zhong Saiyi,Cheong Kit-Leong
Introduction: Research on the mechanism of marine polysaccharide utilization by Bacteroides thetaiotaomicron has drawn substantial attention in recent years. Derived from marine algae, the marine algae polysaccharides could serve as prebiotics to facilitate intestinal microecological balance and alleviate colonic diseases. Bacteroides thetaiotaomicron, considered the most efficient degrader of polysaccharides, relates to its capacity to degrade an extensive spectrum of complex polysaccharides. Polysaccharide utilization loci (PULs), a specialized organization of a collection of genes-encoded enzymes engaged in the breakdown and utilization of polysaccharides, make it possible for Bacteroides thetaiotaomicron to metabolize various polysaccharides. However, there is still a paucity of comprehensive studies on the procedure of polysaccharide degradation by Bacteroides thetaiotaomicron.Methods: In the current study, the degradation of four kinds of marine algae polysaccharides, including sodium alginate, fucoidan, laminarin, and Pyropia haitanensis polysaccharides, and the underlying mechanism by Bacteroides thetaiotaomicron G4 were investigated. Pure culture of Bacteroides thetaiotaomicron G4 in a substrate supplemented with these polysaccharides were performed. The change of OD600, total carbohydrate contents, and molecular weight during this fermentation were determined. Genomic sequencing and bioinformatic analysis were further performed to elucidate the mechanisms involved. Specifically, Gene Ontology (GO) annotation, Clusters of Orthologous Groups (COG) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were utilized to identify potential target genes and pathways.Results: Underlying target genes and pathways were recognized by employing bioinformatic analysis. Several PULs were found that are anticipated to participate in the breakdown of these four polysaccharides. These findings may help to understand the interactions between these marine seaweed polysaccharides and gut microorganisms.Discussion: The elucidation of polysaccharide degradation mechanisms by Bacteroides thetaiotaomicron provides valuable insights into the utilization of marine polysaccharides as prebiotics and their potential impact on gut health. Further studies are warranted to explore the specific roles of individual PULs and their contributions to polysaccharide metabolism in the gut microbiota.
研究领域:
微生物学
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分子生物学
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基因组学
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生物信息学
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营养科学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2020
·
IF 8.109
Shanshan Qiao,Li Bao,Kai Wang,Shanshan Sun,Mingfang Liao,Chang Liu,Nan Zhou,Ke Ma,Yuwei Zhang,Yihua Chen,Shuang-Jiang Liu,Hongwei Liu
Summary A beneficial gut Bacteroides -folate-liver pathway regulating lipid metabolism is demonstrated. Oral administration of a Ganoderma meroterpene derivative (GMD) ameliorates nonalcoholic hepatic steatosis in the liver of fa/fa rats by reducing endotoxemia, enhancing lipid oxidation, decreasing de novo lipogenesis, and suppressing lipid export from the liver. An altered gut microbiota with an increase of butyrate and folate plays a causative role in the effects of GMD. The commensal bacteria Bacteroides xylanisolvens , Bacteroides thetaiotaomicron , Bacteroides dorei , and Bacteroides uniformis, which are enriched by GMD, are major contributors to the increased gut folate. Administration of live B. xylanisolvens reduces hepatic steatosis and enhances the folate-mediated signaling pathways in mice. Knockout of the folate biosynthetic folp gene in B. xylanisolvens blocks its folate production and beneficial effects. This work confirms the therapeutic potential of GMD and B. xylanisolvens in alleviating nonalcoholic hepatic steatosis and provides evidence for benefits of the gut Bacteroides -folate-liver pathway.
研究领域:
胃肠病学
·
微生物学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
Jikai He,Jiaqi Jia,Wenhao Qu,Shuyu Zhang,Keyu Fan,Runze Lin,Wei Zhao,Yan Niu,Yanqiang Huang,Lizhou Jia
Objective To analyze differences in gut microbiota composition, metabolites, and metabolic pathways between healthy individuals and colorectal cancer (CRC) patients, and to investigate the inhibitory effects of N-methylserotonin (NMS) produced by Bacteroides ovatus (B.o) from orange fiber on CRC progression and its underlying mechanisms. Methods (1) Fecal samples from CRC patients (n=26) and healthy controls (n=20) were collected for metagenomic sequencing and untargeted metabolomics analysis; (2) The ability of B.o to produce NMS from orange fiber was validated in vitro ; (3) A CRC mouse model was established using azoxymethane (AOM)/dextran sulfate sodium (DSS) induction, followed by evaluation of body weight, rectal bleeding, colorectal length, tumor number, and intestinal barrier function; (4) Network pharmacology, molecular docking, and western blot analysis were combined to verify the mechanism of action; (5) 16S rRNA sequencing was performed to analyze gut microbiota changes. Results (1) CRC patients showed significantly increased metabolic pathways including glycolysis, methane metabolism, beneficial amino acid degradation, and linoleic acid degradation, along with significantly decreased B.o abundance and NMS levels, which were positively correlated; (2) NMS significantly inhibited CRC cell proliferation, migration, and invasion, while promoting apoptosis; (3) Combined treatment with B.o and orange fiber or NMS alone reduced tumorigenesis and improved intestinal barrier function; (4) Mechanistic studies revealed that these effects could be mediated through downregulation of 5-hydroxytryptamine receptor 1D (HTR1D) expression and inhibition of the cAMP/PKA/IκBα/NF-κB pathway; (5) The treatments optimized gut microbiota structure and metabolite composition. Conclusion B.o and its metabolite NMS possibly inhibit CRC progression by modulating the HTR1D-mediated cAMP/PKA/NF-κB signaling pathway, while improving gut microbiota structure, providing a novel therapeutic target for CRC prevention and treatment.
研究领域:
肿瘤学
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微生物组研究
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分子生物学
·
代谢组学
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胃肠病学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2024
·
IF 6
Zhiqing Xie,Aohuan Huang,Jihang Xie,Shubo Yu,Mengfei Chen,Jie Cai,Rong Huang,Zhenjun Zhu,Yu Ding
Bacteroides dorei is a promising candidate for the next-generation probiotics (NGP), but its accurate identification remains challenging due to its close taxonomic relationship with other Bacteroides species. This study aimed to mine the novel specific molecular target for detecting Bacteroides dorei . Using pan-genome analysis and PCR validation, species-specific target genes with a size of 193 bp were identified, and the specificity of the designed primer pair (30 bp) for this molecular target was confirmed. The PCR assay demonstrated high applicability for detecting target and/or nontarget strains in three simulated food systems, yielding no false-positive or false-negative results. Additionally, a qPCR method was developed for quantifying Bacteroides dorei , with a linear detection range from 1 × 10 8 to 1 × 10 1 CFU/mL and an R 2 value greater than 0.98. This method exhibited accurate and sensitive detection capabilities suitable for both food and feces samples. Overall, our study established PCR and qPCR assays for the rapid identification of Bacteroides dorei , advancing the exploration of Bacteroides species and the application of detection for NGPs in functional foods across various product forms.
研究领域:
微生物学
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分子生物学
·
食品科学
·
益生菌
✓ 已验证
产品关联
DOI
高影响因子
Protein & Cell
·
2024
·
IF 13.6
Ma Wei,Zhang Lu,Chen Weilong,Chang Zhaoxia,Tu Juchuanli,Qin Yuanyuan,Yao Yuwen,Dong Mengxue,Ding Jiajun,Li Siqin,Li Fengkai,Deng Qiaodan,Yang Yifei,Feng Tingting,Zhang Fanrong,Shao Xiying,He Xueyan,Zhang Lixing,Hu Guohong,Liu Quentin,Jiang Yi-Zhou,Zhu Shu,Xiao Zhi,Su Dan,Liu Tong,Liu Suling
Tumor-resident microbiota in breast cancer promote cancer initiation and malignant progression. However, targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail. Here, we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy. ETBF, albeit at low biomass, secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance. Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein. NOD1 was highly expressed on ALDH+ breast cancer stem cells (BCSCs) and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation, thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs. NOD1 inhibition and ETBF clearance increases the chemosensitivity of breast cancer by impairing BCSCs.
研究领域:
肿瘤学
·
微生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CELL CYCLE
·
2024
·
IF 3.4
Jian Yang,Xue Wang,Tao Hu,He Huang,Gang Chen,Bo Jin,Guilin Zeng,Jian Liu
Our previous findings confirmed the high enrichment of Bacteroides fragilis (BF) in fecal samples from patients with colorectal cancer (CRC). The intestinal mucosal barrier is the first defense of the organism against commensal flora and intestinal pathogens and is closely associated with the occurrence and development of CRC. Therefore, this study aimed to investigate the molecular mechanisms through which BF mediates intestinal barrier injury and CRC progression. SW480 cells and a Caco2 intestinal barrier model were treated with entero-toxigenic BF (ETBF), its enterotoxin (B. fragilis toxin, BFT), and non-toxigenic BF (NTBF). Cell counting kit-8, flow cytometry, wound healing and transwell assays were performed to analyze the proliferation, apoptosis, migration, and invasion of SW480 cells. Transmission electron microscopy, FITC-dextran, and transepithelial electrical resistance (TEER) were used to analyze damage in the Caco2 intestinal barrier model. The Azoxymethane/Dextran Sulfate Sodium (AOM/DSS) animal model was established to evaluate the effect of ETBF on intestinal barrier injury and CRC progression in vivo. ETBF and BFT enhanced the viability, wound healing ratio, invasion, and EMT of SW480 cells. In addition, ETBF and BFT disrupted the tight junctions and villus structure in the intestinal barrier model, resulting in increased permeability and reduced TEER. Similarly, the expression of intestinal barrier-related proteins (MUC2, Occludin and Zo-1) was restricted by ETBF and BFT. Interestingly, the STAT3/ZEB2 axis was activated by ETBF and BFT, and treatment with Brevilin A (a STAT3 inhibitor) or knockdown of ZEB2 limited the promotional effect of ETBF and BFT on the SW480 malignant phenotype. In vivo experiments also confirmed that ETBF colonization accelerated tumor load, carcinogenesis, and intestinal mucosal barrier damage in the colorectum of the AOM/DSS animal model, and that treatment with Brevilin A alleviated these processes. ETBF-secreted BFT accelerated intestinal barrier damage and CRC by activating the STAT3/ZEB2 axis. Our findings provide new insights and perspectives for the application of ETBF in CRC treatment.
研究领域:
胃肠病学
·
肿瘤学
·
微生物学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Chun-Qian Zhang,Xia Chen,Kan Ding
Dioscorea opposita Thunb. is widely used as functional foods and traditional Chinese medicine in China for its activity of regulating function of spleen and stomach. Polysaccharides may contribute to the function of regulation. To investigate structure features and bioactivities of polysaccharides from D. opposita, the rhizome of D. opposita was extracted with boiling water, yielding crude polysaccharides DOP. A novel polysaccharide named DOP0.1-S-1 was isolated from DOP by further purification. The average molecular weight of DOP0.1-S-1 was 10,000 Da and the range was around 12,000 –1,200 Da. The carbohydrate content of DOP0.1-S-1 was 100% and no protein was detected. The monosaccharide analysis showed that DOP0.1-S-1 was mostly composed of galactose. Methylation and NMR spectra analysis indicated that DOP0.1-S-1 was a 1,4-β-galactan. Bioactivity test showed that DOP0.1-S-1 could promote the growth of B. thetaiotaomicron and B. ovatus and produce the short-chain fatty acids during the utilization of the polysaccharide.
研究领域:
食品科学
·
微生物学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Gut Microbes
·
2024
·
IF 12.2
Zhenhui Chen,Huijuan Chen,Wanwen Huang,Xiaotong Guo,Lu Yu,Jiamin Shan,Xiaoshi Deng,Jiaxin Liu,Wendan Li,Wei Shen,Hongying Fan
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants with no specific treatments available. We aimed to identify the molecular mechanisms underlying NEC and investigate the therapeutic effects of Bacteroides fragilis on NEC. Clinical samples of infant feces, bile acid-targeted metabolomics, pathological staining, bioinformatics analysis, NEC rat model, and co-immunoprecipitation were used to explore the pathogenesis of NEC. Taxonomic characterization of the bile salt hydrolase (bsh) gene, enzyme activity assays, 16S rRNA sequencing, and organoids were used to explore the therapeutic effects of B. fragilis on NEC-related intestinal damage. Clinical samples, NEC rat models, and in vitro experiments revealed that total bile acid increased in the blood but decreased in feces. Moreover, the levels of FXR and other bile acid metabolism-related genes were abnormal, resulting in disordered bile acid metabolism in NEC. Taurochenodeoxycholic acid accelerated NEC pathogenesis and taurodeoxycholate alleviated NEC. B. fragilis displayed bsh genes and enzyme activity and alleviated intestinal damage by restoring gut microbiota dysbiosis and bile acid metabolism abnormalities by inhibiting the FXR-NLRP3 signaling pathway. Our results provide valuable insights into the therapeutic role of B. fragilis in NEC. Administering B. fragilis may substantially alleviate intestinal damage in NEC.
研究领域:
微生物学
·
胃肠病学
·
儿科
·
代谢组学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Lisi Liang,Lianzhu Lin,Mouming Zhao
Lycium barbarum polysaccharide (LBP) is a prebiotic that promotes the proliferation of beneficial bacteria, but lacks of regulatory function on harmful bacteria. In this study, chlorogenic acid (CGA) was used to achieve the functional enhancement of two LBPs (LBP-A and LBP-M). The combination of CGA resulted in changes in the solution properties of LBPs, manifested as increased pseudoplasticity, viscosity, turbidity, and decreased water mobility, absolute potential value, pH value. CGA was non-covalently bound to LBPs through hydrophobic interaction and hydrogen bond. LBP-A had strong affinity with CGA, mainly through hydrophobic interaction, while LBP-M had weak affinity with CGA, mainly through hydrogen bond. Both LBP-CGA complexes exhibited Bacteroides proliferative activity and gut pathogens inhibitory activity, among which LBP-A-CGA complex showed strong inhibitory effects on Escherichia coli and Bacillus cereus , and LBP-M-CGA complex showed strong inhibitory effect on Staphylococcus aureus . This study provided guidance for the development of LBP-CGA as novel prebiotic.
研究领域:
食品科学
·
微生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）