Journal of Clinical and Translational Hepatology
·
2023
·
IF 3.6
Fulin Nian,Longyun Wu,Qiaoyun Xia,Peiying Tian,Chunmei Ding,Xiaolan Lu
Background and aims Non-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota and has become the most common chronic liver disease worldwide, but the relationship between specific strains and NAFLD has not been fully elucidated. We aimed to investigate whether Akkermansia muciniphila and Bifidobacterium bifidum could prevent NAFLD, the effects of their action alone or in combination, possible mechanisms, and modulation of the gut microbiota. Methods Mice were fed with high-fat diets (HFD) for 20 weeks, in which experimental groups were pretreated with quadruple antibiotics and then given the corresponding bacterial solution or PBS. The expression of the glycolipid metabolism indicators, liver, and intestinal farnesol X receptors (FXR), and intestinal mucosal tight junction proteins were detected. We also analyzed the alterations of inflammatory and immune status and the gut microbiota of mice. Results Both strains were able to attenuate mass gain ( p <0.001), insulin resistance ( p <0.001), and liver lipid deposition ( p <0.001). They also reduced the levels of the pro-inflammatory factors ( p <0.05) and the proportion of Th17 ( p <0.001), while elevating the proportion of Treg ( p <0.01). Both strains activated hepatic FXR while suppressing intestinal FXR ( p <0.05), and elevating tight junction protein expression ( p <0.05). We also perceived changes in the gut microbiota and found both strains were able to synergize beneficial microbiota to function. Conclusions Administration of A. muciniphila or B. bifidum alone or in combination was protective against HFD-induced NAFLD formation and could be used as alternative treatment strategy for NAFLD after further exploration.
研究领域:
微生物学
·
肝病学
·
营养学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Zheming Gu,Xin Tang,Bingyong Mao,Qiuxiang Zhang,Jianxin Zhao,Wei Chen,Shumao Cui
Bifidobacterium bifidum rarely utilises yeast extract , which causes significant challenges in its industrial production. This study characterised the utilisation of amino acids by B. bifidum to improve the viability of the strain. In this study, the proliferation effect of B. bifidum in different nitrogen sources was determined, and the amino acid contents of different nitrogen sources were analysed, which indicated that hydrophobic amino acids may inhibit B. bifidum growth. Among different hydrophobic amino acids , methionine was identified as the strongest growth inhibitor. Furthermore, the intracellular pH and NH 4 + contents of B. bifidum CCFM16 were higher in methionine-free medium. Among the NH 3 -producing enzymes related to amino acid metabolism , the metC gene was significantly transcribed in methionine-free medium. In addition, tcyP , metB , metC and metE genes encoding cysteine transporter proteins and the conversion pathway of cysteine to methionine were transcribed 2.03-fold, 7.03-fold, 3.05-fold and 2.92-fold, respectively, in methionine-free medium compared to methionine-containing medium. Compared with methionine-containing medium, the activity of tricarboxylic acid cycle rate-limited enzyme isocitrate dehydrogenase in methionine-free medium also increased from 198.89 to 410.56 nmol/min/mg protein, which probably enhanced the carbon flux and promoted growth. Meanwhile, the activity of pyrroline-5-carboxylate reductase , an enzyme that synthesises proline , increased from 14.76 to 35.28 nmol/min/mg protein, which promoted proline synthesis in response to osmotic stress . Cyclopropane fatty acids were also significantly higher in methionine-free medium, which may promote growth by decreasing cell membrane permeability to protons and enhancing cell membrane fluidity . This study provides a theoretical basis for high-density culture of B. bifidum .
研究领域:
微生物学
·
生物化学
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yu Tang,Chun Chen,Binglei Jiang,Lu Wang,Fujie Jiang,Disen Wang,Yaotai Wang,Haiyan Yang,Xia Ou,Yan Du,Qi Wang,Jianzhong Zou
Purpose Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for Bifidobacterium bifidum (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer.Methods We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF in vivo. Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor.Results The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects.Conclusion We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.
研究领域:
癌症治疗
·
纳米医学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Tingting He,Lu Wang,Shuangquan Gou,Lu Lu,Genhua Liu,Kui Wang,Yulu Yang,Qiaojian Duan,Wenbo Geng,Peng Zhao,Zhong Luo,Kaiyong Cai
The immunogenic cell death (ICD) of tumor cells has aroused great interest in the field of immunotherapy, mainly due to the production of plentiful tumor-associated antigens (TAAs) and damage-associated molecule patterns. However, doxorubicin (DOX)-induced tumor-specific T-cell-mediated immune response is usually very weak because of antigen presentation deficiency and the immunosuppressive tumor microenvironment (ITME). Herein, the probiotic Bifidobacterium bifidum (Bi) was covalently modified with DOX-loaded CaP/SiO2 nanoparticles (DNPs@Bi) for tumor therapy. On one hand, the pH-responsive release of DOX could induce chemotherapy and ICD in the ITME. On the other hand, tumor-targeting Bi is able to significantly enhance the presentation of TAAs from B16F10 cells to DCs via Cx43-dependent gap junctions. Due to the combination of enhanced ICD and TAAs presentation, the maturation of DCs and the infiltration of cytotoxic T lymphocytes in the ITME were stimulated. As a result, in vivo antitumor experiments demonstrated that DNPs@Bi prolonged the survival rate and significantly inhibited the tumor progression and metastasis. This strategy of bacterial-driven hypoxia-targeting delivery systems offers a promising approach to tumor chemo-immunotherapy.
研究领域:
肿瘤学
·
免疫治疗
·
纳米技术
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 19
·3054
·
IF 4.7
Jiacui Shang,Lijun Liu,Shuo Yang,Bofan Duan,Shuiqi Xie,Xiangchen Meng
Chronic inflammation is a factor in the development of cancer, and probiotics play a role in preventing or treating inflammation as an adjuvant therapy. To investigate potential probiotics for the prevention of colitis-associated colorectal cancer (CAC), Bifidobacterium bifidum H3-R2 and Lactococcus lactis KLDS4.0325 were used to examine the effects on colon cancer cells and in an inflammation-related cancer animal model. The results revealed that B. bifidum H3-R2 in combination with L. lactis KLDS4.0325 caused apoptosis in colon cancer cells by increasing caspase-3 and caspase-9 protein levels, enhancing Bax expression, and lowering Bcl-2 expression. In addition, the combination of the two strains relieved the tissue damage; reduced proinflammatory cytokines, myeloperoxidase (MPO) activity, and hypoxia-inducible factor 1-alpha (HIF-1α) level; upregulated anti-inflammatory cytokines; increased colonic tight junction protein expression; regulated intestinal homeostasis by inhibiting NLRP3 inflammasome signaling pathway; and improved the imbalance of gut microbiota in animal models. Moreover, the combination of the two strains had a greater preventive impact than each strain alone. These findings are supportive of clinical studies and product development of multi-strain probiotic preparations for diseases associated with colitis.
研究领域:
微生物学
·
癌症研究
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
BIOCATALYSIS AND BIOTRANSFORMATION
·
2020
·
IF 1.863
Chou Li,Qingzhi Ji,Tongyao He,Yingying Liu,Yunqing Ma
Deconjugation of bile salts in vivo not only promotes the cholesterol metabolism of the host, but also provides cellular carbon, nitrogen and sulphur for some probiotics. In this study, the gene of BSH from Bifidobacterium bifidum (ATCC 29521) was amplified and expressed using glutathione S-transferase (GST) Gene Fusion System. The enzyme was purified in a mild conditions without denaturation and renaturation, and the molecular mass was estimated to be 35 kDa. The optimum pH for the enzyme catalysis was 5.5. The BSH enzyme was stable from 37 to 57 °C. In addition, this enzyme was completely inhibited by Cu2+, while many other metal ions only gave moderate inhibition. Hydrolysis efficiency of BSH was quantified in two ways: ninhydrin colouration method and high-performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD). The hydrolysis process was clearly observed through real-time picture monitoring. The activity of BSH on glycine-conjugated bile salts was better than on taurine-conjugated bile salts. The proportion of hydrolysis for both sodium glycochenodeoxycholate (GCDCA) and sodium glycoursodeoxycholate (GUDCA) were more than 90% in 60 min. However, the proportion of hydrolysis for sodium taurochenodeoxycholate (TCDCA) and sodium tauroursodeoxycholate (TUDCA) were only 68% and 43% at the same condition. The study of this paper provides a better choice for hydrolysis of glycine-conjugated bile salts.HighlightsThe specificity of BSH was high for glycine-conjugated bile salts.Hydrolysis process of bile acid was obtained through real-time picture monitoring.Hydrolysis efficiency of BSH was quantified in two ways: ninhydrin colouration method and HPLC-ELSD.
研究领域:
微生物学
·
酶学
·
益生菌研究
·
代谢
✓ 已验证
产品关联
DOI
高影响因子
PROCESS BIOCHEMISTRY
·
2026
·
IF 4.4
Nanyu Tang,Tao Lin,Chang Xu,Xia Fan,Kai Ma,Changliang Zhang,Shuo Geng,Feng Ji,Xin Rui,Wei Li
This study investigates the production and prebiotic properties of exopolysaccharides (EPS) from Bifidobacterium bifidum 3469 (BBF-EPS) and B. animalis subsp. lactis 9749 (BAL-EPS). To eliminate interference from exogenous polysaccharides present in conventional MRS-c broth, EPS were produced using a modified medium (MRS-TY) lacking complex carbohydrate components, enabling accurate structural characterization of the intrinsically synthesized EPS. Whole-genome sequencing revealed fundamentally different eps biosynthetic gene clusters between the strains. The structural analysis indicated that the compact gene cluster of B. bifidum 3469 was associated with a simpler EPS (molecular weight 1.98 ×10 5 Da; consisting of glucose, galactose, rhamnose, and mannose in a 1.00:0.78:0.34:0.25 molar ratio), whereas the large, complex cluster of B. animalis subsp. lactis 9749 was associated with the production of a galactose-rich EPS (molecular weight 2.02 ×10 5 Da; consisting of galactose, rhamnose, glucose, and mannose in a 5.47:1.46:1.00:0.86 molar ratio). Both EPS supported growth of Lactobacillus strains. In vitro fecal fermentation demonstrated that BBF-EPS enriched Megamonas and Faecalibacterium , leading to increased propionic acid production (51.77 mM). In contrast, BAL-EPS enriched Bifidobacterium and Blautia , enhancing butyric acid (28.67 mM) production. These findings highlight the importance of culture medium optimization for reliable characterization of bifidobacterial EPS, supporting their potential application as targeted prebiotics for intestinal health.
✓ 已验证
DOI
高影响因子
Biomaterials Advances
·
2026
·
IF 6.7
Mengyao Li,Yuwen Yan,Tianxing Gong,Xinwei Liu,Yi Liu,Bowen Zheng
Oral ulcers affect over 25% of the global population, substantially impairing quality of life. Current therapeutic approaches are limited by challenges such as drug resistance and treatment dependency. Although probiotics have shown promise in mucosal repair, local delivery of anaerobic strains such as Bifidobacterium bifidum remains challenging because oxygen exposure rapidly reduces bacterial viability. Here, we report a sprayable, dynamic Schiff-base gelatin/cellulose hydrogel capable of in situ gelation and microenvironment engineering for the viable delivery of Bifidobacterium bifidum . The reversible imine crosslinking network forms an oxygen-limited, moisture-retaining niche that preserves bacterial viability while enabling uniform mucosal adhesion and deformation tolerance. B. bifidum embedded in the hydrogel exhibited sustained release over 2 h and maintained high activity throughout gelation and degradation. In vitro, the hydrogel and B. bifidum synergistically enhanced fibroblast migration, reduced LPS-induced TNF-α and IL-6 expression, and promoted macrophage polarization toward the M2 phenotype. In vivo, the B. bifidum –loaded hydrogel markedly accelerated oral ulcer closure, improved epithelial regeneration, increased collagen deposition, and elevated α-SMA and collagen I expression. Cytokine profiling confirmed a transition toward a pro-healing microenvironment characterized by decreased TNF-α/IL-6 and increased IL-10 levels. No systemic toxicity was observed. This work demonstrates a microbe–material synergy strategy, where a dynamic covalent hydrogel enables anaerobic probiotic therapy by engineering a protective oxygen-limited microenvironment. The platform offers a clinically translatable approach for managing oral mucosal wounds under complex wet conditions.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2022
·
IF 6.064
Chenrui Peng,Jinxing Li,Zhonghua Miao,Yunyi Wang,Simou Wu,Yimei Wang,Silu Wang,Ruyue Cheng,Fang He,Xi Shen
Inflammatory bowel disease (IBD) is a chronic intestinal disease characterized by microbiota disturbance and intestinal mucosal damage. The current study aimed to investigate the preventive effects of Bifidobacterium bifidum BD-1 (BD-1) against long-term IBD and possible mechanism by which it alters the gut microbiota, immune response, and mucosal barrier. Our study found that early treatment of BD-1 + Ceftri (ceftriaxone followed by BD-1) and BD-1 confers a certain protective effect against the occurrence of long-term Dextran sulfate sodium-induced colitis, which manifests as a decrease in inflammation scores and MPO activity levels, as well as a relatively intact intestinal epithelial structure. Moreover, compared to BD-1, Ceftri, and NS, early treatment with BD-1 + Ceftri promoted greater expression levels of mucosal barrier-related proteins [KI67, MUC2, ZO-1, secretory immunoglobulin A (slgA), Clauding-1, and Occludin], better local immune responses activation, and moderately better modulation of systemic immune responses during long-term colitis. This may be due to the fact that BD-1 + Ceftri can deliberately prolong the colonization time of some beneficial microbiota (e.g., Bifidobacterium ) and reduce the relative abundance of inflammation-related microbiota (e.g., Escherichia/Shigella and Ruminococcus ). Interestingly, we found that the changes in the gut barrier and immunity were already present immediately after early intervention with BD-1 + Ceftri, implying that early effects can persist with appropriate intervention. Furthermore, intervention with BD-1 alone in early life confers an anti-inflammatory effect to a certain degree in the long-term, which may be due to the interaction between BD-1 and the host’s native gut microbiota affecting intestinal metabolites. In conclusion, BD-1 was not as effective as BD-1 + Ceftri in early life, perhaps due to its failure to fully play the role of the strain itself under the influence of the host’s complex microbiota. Therefore, further research is needed to explore specific mechanisms for single strain and native microbiota or the combination between probiotics and antibiotics.
研究领域:
微生物学
·
免疫学
·
胃肠病学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Chenrui Peng,Chang Lu,Xiaoting Li,Lunpu Zhang,Yao Zeng,Xiaona Wu,Ting Wu,Fang He,Xi Shen
Purpose Early-life gut microbiota establishment critically influences long-term host health. This study investigated whether maternal Bifidobacterium bifidum BD-1 supplementation during late gestation, combined with delivery mode, affects offspring responses to DSS-induced acute colitis. Methods Pregnant mice received B. bifidum BD-1 (1×10^9 CFU/day), ceftriaxone (100 mg/kg), or saline by gavage from gestational day 14 to 21. Offspring were delivered vaginally (VD) or by cesarean section (CS). Acute DSS-induced colitis was induced with 3% dextran sulfate sodium at postnatal day 42. Results VD offspring showed relatively stable microbial succession and comparatively limited variation in DSS-induced colitis-related outcomes across maternal treatment groups. In CS offspring, maternal BD-1 supplementation was associated with enrichment of beneficial genera, maintenance of α-diversity, higher fecal butyrate and propionate levels, increased expression of tight junction-related genes, and lower histopathological inflammatory scores compared with NS-CS-DSS offspring. Conclusion Maternal B. bifidum BD-1 supplementation was associated with lower indices of acute DSS-induced colitis, with more pronounced effects observed in CS offspring, supporting its potential as a prenatal probiotic candidate requiring further validation.
✓ 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）