Gut Microbes
·
2025
·
IF 11
Yong Sun,Qiwen Wang,Yao Jiang,Jiamin He,Dingjiacheng Jia,Man Luo,Wentao Shen,Qingyi Wang,Yadong Qi,Yifeng Lin,Ying Zhang,Lan Wang,Liangjing Wang,Shujie Chen,Lina Fan
Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, the deep mechanism between the microbiota-TME interaction has not been well explored. In this study, we for the first time discovered that Lactobacillus intestinalis (L. intestinalis) effectively suppressed tumor growth both in the AOM/DSS-induced CRC model and the ApcMin/+ spontaneous adenoma model. Our investigation revealed that L. intestinalis increased the infiltration of immune cells, particularly dendritic cells (DC), in the TME. Mechanically, the tumor-derived CCL5 induced by L. intestinalis recruited DC chemotaxis through the NOD1/NF-κB signaling pathway. In clinical samples and datasets, we found positive correlation between L. intestinalis, CCL5 level, and the DC-related genes. Our study provided a new strategy for microbial intervention for CRC and deepened the understanding of the interaction between tumor cells and the immune microenvironment modulated by gut microbes.
研究领域:
肿瘤学
·
微生物学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
INFLAMMOPHARMACOLOGY
·
2025
·
IF 5.3
Xu Wenxiu,Wang Hongbo,Sun Zhenyu,Zhang Hui,Zhang Zhijun,Sun Xiangrong,Gu Jiayu,Gong Yanling
Limonene, a monoterpene naturally abundant in various Citrus fruits, is widely used as a fragrance component and dietary supplement. Ulcerative colitis (UC), a representative inflammatory bowel disease, is characterized by an arising incidence and considerable impact on human health. Although several reports have demonstrated the beneficial effects of limonene on UC, detailed mechanisms remain incompletely understood. In this study, we employed a dextran sulfate sodium (DSS)-induced UC murine model and a lipopolysaccharide (LPS)-stimulated Caco-2 cell model to explore the mechanisms of limonene on UC. The results revealed that limonene significantly decreased disease activity index (DAI) score and alleviated pathological damage in UC mice, exhibiting therapeutic potential for UC. Limonene significantly inhibited interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) while increased superoxide dismutase (SOD) in both DSS-induced UC mice and LPS-induced Caco-2 cells. Furthermore, limonene significantly increased expressions of Zonula occludens-1 (ZO-1), occludin, and claudin-1, thereby enhancing intestinal barrier integrity. Limonene mitigated UC-associated dysbiosis by shifting the gut microbial composition toward that of healthy controls. Specifically, it modulated the microbiota at the phylum, family, genus and species levels, increasing the abundance of anti-inflammatory bacteria while decreasing inflammatory related taxa. Collectively, our in vivo and in vitro results demonstrate that limonene alleviates UC involving in anti-inflammation, anti-oxidation, restoration of intestinal barrier integrity and regulation of the gut microbiota. Future studies are warranted to explore whether gut microbial metabolites contribute to the protective effects of limonene in UC. Graphical abstract
研究领域:
消化病学
·
免疫学
·
分子生物学
·
药理学
·
微生物组学
·
氧化应激
·
肠道屏障功能
·
天然产物药理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BioScience Trends
·
2026
·
IF 5
Fangzhou Dou,Jing Li,Daoran Lu,Yueyi Sun,Shasha Hu,Jianjun Gao
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options. Transient receptor potential ankyrin 1 (TRPA1) has been implicated in inflammation and pain, but its role in UC remains a subject of debate. The current study investigated the effects of TRPA1 inhibition in both acute and subacute murine models of dextran sulfate sodium (DSS)-induced colitis. Genetic knockout of Trpa1 or pharmacological inhibition with A967079 significantly ameliorated inflammation in the acute model, reducing the disease activity index (DAI), colon shortening, histopathological damage, and TNF-α secretion from macrophages. In contrast, TRPA1 suppression exacerbated subacute colitis and worsened weight loss, DAI, colon shortening, and histopathology. Mechanistically, Trpa1 deletion promoted CD4+ T cell polarization toward the Th1 subtype in subacute colitis, increasing IFN-γ levels. These findings reveal a dual role for TRPA1 in colonic inflammation: it mediates pro-inflammatory effects primarily via innate immune cells in the acute phase but has anti-inflammatory effects by modulating adaptive immunity in the subacute phase. These findings provide new insights into the context-dependent roles of TRPA1 and suggest that TRPA1 may represent a context-specific and stage-dependent therapeutic target in UC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2022
·Vol. 10
·期 3
·
IF 9.043
Xiaojun Li,Yu Ren,Jie Zhang,Chunhui Ouyang,Chunlian Wang,Fanggen Lu,Yani Yin
Early-life gastrointestinal microbiota development is crucial for physiological development and immunological homeostasis. In the current study, perinatal microbiota and the development of gastrointestinal microbiota in different early-life periods (perinatal, lactation, and postweaning nutrition periods) were explored by using an antibiotic-interfered mouse model and a dextran sulfate sodium-induced colitis mouse model. Gut microbiota samples were collected from mother mice and litters. The results of 16S rRNA gene sequences suggested that microbiota in the gastrointestinal system were present in prenatal fetal mice, and microbiota structures in different parts of the gastrointestinal system of the fetal mice were similar to those in the corresponding gut parts of maternal mice. Microbiota in mucus samples from different regions exhibited higher diversity at birth than at other periods and varied substantially over time with diet change. Moreover, antibiotic treatment in early life affected the composition and diversity of gastrointestinal microbiota in adult mice and enhanced susceptibility to experimental colitis in mice, particularly in the lactation period. This approach of exploring gut microbiota evolution is hoped to provide an enhanced view of how resident microbiota develop in early life, which in turn might facilitate understanding of gut microbiota and related diseases.IMPORTANCE This study investigated resident microbiota in the whole gastrointestinal (GI) tract to explore gut microbiota development in early life and found that early-life antibiotic exposure exacerbated alterations in gut microbiota and murine dextran sulfate sodium (DSS)-induced colitis. Furthermore, the presence of bacteria in the GI tract of mice before birth and the importance of the lactation period in GI microbiota development were confirmed.
研究领域:
微生物学
·
免疫学
·
分子生物学
·
营养学
·
转化医学
✓ 已验证
DOI
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Yutong Ma,Jiaxi Li,Shuyu Liu,Wenlong Yu,Yaxin Sang,Xianghong Wang
Sulforaphane (SFN), a bioactive compound derived from cruciferous vegetables, exhibits chemopreventive properties agains various malignancies. Colitis-associated colorectal cancer (CAC) is a malignancy that develops through chronic inflammation-driven carcinogenesis in patients with long-standing inflammatory bowel disease. This study demonstrates a novel mechanism by which SFN protects against CAC through the simultaneous regulation of the Wnt/β-catenin signaling pathway and gut microbiota. Using an azoxymethane(AOM)/dextran sulfate salt sodium(DSS)-induced CAC mouse model to systematically evaluate SFN's therapeutic potential. Comprehensive assessments included histopathological examination, molecular analysis of inflammatory cytokines and proliferation markers, 16S rDNA sequencing for gut microbiota characterization, short-chain fatty acid (SCFA) profiling, and mechanistic investigation of Wnt/β-catenin pathway components. The experimental results showed that SFN intervention significantly alleviated clinical symptoms in mice, reduced inflammatory cytokine levels (IFN-γ, interferon-gamma; IHC, immune histochemical; IL-17, interleukin-17; IL-6, interleukin-6; MPO, myeloperoxidase) and suppressed proliferation markers (PCNA, proliferating cell nuclear antigen, antigen identified by monoclonal antibody Ki-67, Ki-67). Notably, SFN administration significantly restored the levels of major SCFAs, including acetate, propionate, and butyrate, which were markedly reduced in CAC mice. Mechanistically, SFN inhibited the Wnt/β-catenin signaling pathway by down-regulating the expression of β-catenin, cyclin D1 and c-myc expression. Concurrently, SFN restored gut microbial diversity, increased beneficial bacteria, and reduced pathogenic genera. The observed increase in SCFAs levels was correlated with these microbial improvements, and orrelation analysis further linked these microbial shifts to clinical improvements. Our findings reveal that SFN mitigates CAC progression by coordinated modulation of both Wnt/β-catenin signaling and gut microbiota, with the restoration of SCFAs production representing a key functional outcome, highlighting its potential as a multi-target dietary intervention for colorectal cancer prevention.
✓ 已验证
产品关联
DOI
高影响因子
Food Frontiers
·
2025
·
IF 6.9
Yanqi Peng,Ji Wu,Ronghua Fan,Mingyue Ma,Xixin Wang,Yuzhen Pi,Xiqing Yue,Yanyu Peng
The development of new therapeutic strategies for ulcerative colitis (UC) requires the targeting of multiple pathogenic factors, including disruption of the colonic mucosal barrier, dysregulated inflammation, and gut microbiota imbalance. This study aimed to investigate the protective mechanisms of almond polysaccharide (AP1) against dextran sulfate sodium (DSS)-induced UC in mice. Administration of AP1 significantly restored DSS-induced reductions in goblet cells and inhibited epithelial apoptosis, thereby preserving colonic mucosal barrier integrity. In addition, AP1 decreased the levels of proinflammatory cytokines and oxidative stress markers in colonic tissues. Gut microbiota analysis revealed that AP1 effectively restored microbial composition and diversity. Furthermore, AP1 increased the relative abundance of beneficial bacteria while reducing pathogenic taxa, thereby contributing to the restoration of intestinal microbial balance in UC mice. Metabolomic analysis of short-chain fatty acids (SCFAs) demonstrated that DSS-induced UC significantly depleted major SCFAs (acetic acid, propionic acid, n-butyric acid) and disrupted branched-chain fatty acid (i-butyric acid and i-valeric acid) metabolism, whereas AP1 intervention reestablished SCFA profiles. Correlation analysis showed Bacteroides negatively correlated with multiple SCFAs, whereas Alistipes positively correlated with propionic acid. Collectively, these findings underscore the role of AP1 in rescuing microbiota-derived SCFA metabolism. In summary, AP1 was shown to alleviate UC symptoms through multiple mechanisms, including the preservation of mucosal barrier integrity, suppression of oxidative stress and inflammation, and modulation of gut microbiota composition and the intestinal microenvironment. These results support the therapeutic potential of AP1 as a natural polysaccharide-based agent for UC treatment.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Weisong Wu,Limei Liu,Yingwei Zhu,Jingbin Ni,Jian Lu,Xiaoli Wang,Li Ma,Yanjun Jiang
In patients suffering from inflammatory bowel diseases (IBDs), the immune system is disrupted and the intestinal barrier function is compromised. Here, six zinc-flavonoid particles were produced by one-step reaction via changing flavonoids (myricetin, quercetin, and rutin) and solvent (water and ethanol), and then their cytocompatibility and ability to scavenge H2O2, free radicals, and LPS-induced ROS were compared. Zinc-rutin particles (W-ZnRT) composed of rutin (78.92 wt %), Na12[ZnPO4]12·12H2O (6.76 wt %), and crystal water were screened out because W-ZnRT exhibited 80.8 ± 15% cell viability against RAW264.7, could rapidly scavenge 78.1 ± 1% of H2O2 and 71.6 ± 2% of DPPH within 30 min, and reduced LPS-increased intracellular ROS to normal levels. In addition, the therapeutic effects of rutin and W-ZnRT were also compared in dextran sulfate sodium (DSS)-induced acute and chronic colitis in mice. W-ZnRT was superior to rutin alone in chronic colitis (n = 9), although they were equally effective in acute colitis (n = 7). Compared to rutin, 11 oral doses of W-ZnRT (40 mg kg–1) significantly improved intestinal permeability (p = 0.0299) and colon length (p = 0.0025), reduced intestinal proinflammatory factors (IL-6, IL-1β, and TNF-α), and upregulated tight junction proteins to maintain intestinal barrier function. Taken together, these results identified W-ZnRT as an efficient and safe therapeutic strategy for IBD.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Xinyu Jiang,Yongliang Ma,Feng Gao,Yali Yu
The intestinal barrier-protective efficacy of quercetin (Que) is limited by its poor gastrointestinal stability and insufficient bioaccessibility. To overcome this, we engineered a dual-fibril gel delivery system for Que, termed QTC, through the assembly of tiger-nut protein fibrils and carboxylated cellulose nanofibrils. In the DSS-induced intestinal barrier injury mouse model, QTC outperformed free Que in preserving intestinal mucosal architecture and mitigating epithelial damage. It markedly restored intestinal barrier integrity, reflected by the upregulation of tight-junction proteins and reduced intestinal permeability. Furthermore, QTC effectively suppressed inflammatory responses and oxidative stress, thereby maintaining barrier homeostasis. Notably, QTC intervention positively modulated the gut microbiota, enriching for beneficial genera and boosting short-chain fatty acid production. Collectively, our findings demonstrate that the novel QTC gel significantly amplified the intestinal barrier-protective effects of Que. This study provides an effective food-grade delivery strategy to enhance the efficacy of polyphenols for gut health management.
✓ 已验证
DOI
PubMed
高影响因子
Cellular and Molecular Gastroenterology and Hepatology
·
2024
·
IF 7.1
Liang Wang,Jinsong Li,Mingshan Jiang,Yue Luo,Xiaoke Xu,Juan Li,Yang Pan,Hu Zhang,Zhi-Xiong Jim Xiao,Yang Wang
Background and Aims Dysfunction of the intestinal epithelial barrier comprising the junctional complex of tight junctions and adherent junctions leads to increased intestinal permeability, which is a major cause of uncontrolled inflammation related to Inflammatory Bowel Disease (IBD). The NAD + -dependent deacetylase SIRT1 is implicated in inflammation and the pathological process of IBD. We aimed to elucidate the protective role and underlying mechanism of SIRT1 in cell-cell junction and intestinal epithelial integrity. Methods The correlation of SIRT1 expression and human IBD was analyzed by GEO or immunohistochemical analyses. BK5.mSIRT1 transgenic mice and WT mice were given dextran sodium sulfate (DSS) and the manifestation of colitis-related phenotypes were analyzed. Intestinal permeability was measured by FITC-Dextran and cytokines expression was analyzed by QPCR. The expression of the cell junction-related proteins in DSS-treated or SIRT1-knockdown Caco2 or HCT116 cells was analyzed by Western blotting. The effects of Nicotinamide mononucleotide (NMN) in DSS-induced mice colitis were investigated. Correlations of the SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway with human IBD samples were analyzed. Results Reduced SIRT1 expression is associated with human IBD specimens. SIRT1 transgenic mice exhibit much-reduced manifestations of DSS-induced colitis. the activation of SIRT1 by NMN bolsters intestinal epithelial barrier function and ameliorates DSS-induced colitis in mice. Mechanistically, DSS down-regulates SiRT1 expression, leading to destabilization of β-TrCP1 and upregulation of Snail1, accompanied by reduced expression of E-cadherin, Occludin, and Claudin-1, consequently resulting in increased epithelial permeability and inflammation. The deregulated SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway correlates with human IBD. Conclusion SIRT1 is pivotal in maintaining the intestinal epithelial barrier integrity via modulation of the β-TrCP1-Snail1-E-cadhein/Occludin/Claudin-1 pathway.
研究领域:
胃肠病学
·
免疫学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 8
·1-10
·
IF 8.1
Zhu Chen,Weng Qingyu,Gao Shenwei,Li Fei,Li Zhouyang,Wu Yinfang,Wu Yanping,Li Miao,Zhao Yun,Han Yinling,Lu Weina,Qin Zhongnan,Yu Fangyi,Lou Jiafei,Ying Songmin,Shen Huahao,Chen Zhihua,Li Wen
Eosinophils, traditionally associated with allergic phenomena, play a pivotal role in inflammatory responses. Despite accumulating evidence suggesting their pro-inflammatory function upon activation, the underlying mechanisms governing eosinophil activation remain incompletely characterized. In this study, we investigate the local activation of pulmonary and colon eosinophils within the inflammatory microenvironment. Leveraging transcriptional sequencing, we identify TGF-β as a putative regulator of eosinophil activation, leading to the secretion of granule proteins, including peroxidase. Genetic deletion of TGF-β receptors on eosinophils resulted in the inhibition of peroxidase synthesis, affirming the significance of TGF-β signaling in eosinophil activation. Using models of HDM-induced asthma and DSS-induced colitis, we demonstrate the indispensability of TGF-β-driven eosinophil activation in both disease contexts. Notably, while TGF-β signaling did not significantly influence asthmatic inflammation, its knockout conferred protection against experimental colitis. This study delineates a distinct pattern of eosinophil activation within inflammatory responses, highlighting the pivotal role of TGF-β signaling in regulating eosinophil behavior. These findings deepen our comprehension of eosinophil-related pathophysiology and may pave the way for targeted therapeutic approaches in allergic and inflammatory diseases.
研究领域:
免疫学
·
炎症
·
过敏
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 9
·8259-8272
·
IF 4.171
Shuhua Shan,Yue Xie,Chengying Zhang,Bin Jia,Hanqing Li,Zhuoyu Li
Homology of medicine and food-zizyphi spinosi semen (ZSS) exhibits abundant pharmacological activities, such as sedation, hypnosis and anti-depression. In the present study, the water soluble polyphenols extracted from ZSS via the acid digestion method were named ZSSP, and exhibited significant anti-colorectal cancer (CRC) activity, characterized by restraining cell proliferation, promoting cell apoptosis and increasing chemo-sensitivity of CRC cells. The potential of ZSSP in vivo was further evaluated in an AOM/DSS-induced colitis-associated carcinogenesis (CAC) mouse model. Intriguingly, ZSSP diminished the number and volume of CAC polyps in mice in a dose-dependent manner, and effectively limited the damage of mice organs induced by AOM/DSS. The immunohistochemistry result showed that the elevated CRC early markers in CAC mice, such as COX-II, EMR1, and Ki67, were potently prevented by the ZSSP treatment. Further, the component in ZSSP with the anti-CRC activity was identified as spinosin by the macroporous resin of SP207 and RP-HPLC-MS/MS. Interestingly, during the extraction process, sodium ions were introduced forming spinosin·Na+, which had better water solubility and more remarkable anti-CRC activity than the spinosin. This study provides a new pharmacological property of spinosin derived from ZSS, inhibiting the growth of human CRC cells and colitis-associated CRC in mice, which indicates its potential use as a natural agent against CRC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Jingya Ruan,Huimin Li,Mengqi Lu,Mimi Hao,Fan Sun,Haiyang Yu,Yi Zhang,Tao Wang
Background Jujube, a popular fruit from the Rhamnaceae family, relieves colorectal inflammation caused by spleen deficiency and has been used in many formulas in clinical for decades to treat colorectal cancer (CRC). As of yet, the therapeutic substances and mechanism of their action are unknown. Purpose The purpose of this study is to define the therapeutic substances of jujube and its mechanism of action in treating CRC . Methods The pharmacological effects of jujube extract and its fractions were evaluated in vivo using a CRC mouse model induced by AOM/DSS. The DAI value, colon length, mortality, tumor burden, and histological tumor size of the treated animals were compared. To explore the potential therapeutic substances, LC-MS analysis was conducted to characterize the serum migration components. A network pharmacology experiment was carried out for potential molecular targets. To verify the therapeutic substances as well as the molecular mechanism of jujube intervening CRC, cellular MTT assay of the serum migration components, Western blot and IHC tests were conducted. Results The in vivo pharmacological studies showed that compared to AOM/DSS treated mice, the mortality and DAI value, tumor burden, and histological tumor size of jujube extract and its fat-soluble fraction (mainly contained triterpenes) treated mice were significantly reduced, and their colon lengths were obviously longer than AOM/DSS treated mice. The targeted-LC/MS analysis supposed triterpenes 3, 7, 9, 11, 12, 14, 17 – 21, and 25 – 28 to be the serum migration components, which might be the potential therapeutic substances. In the network pharmacology experiment, the GO annotation and enrichment analysis of the KEGG pathway indicated that PI3K-Akt pathway and inflammatory reaction were important factors for jujube inhibiting CRC. Cellular MTT assay of serum migration components indicated that the potential effective substances from fat-soluble fraction to be triterpenes 3, 7, 17, 19, 20, and 25. The Western blot and IHC assays implied that the jujube extract, its fat-soluble fraction, and triterpenes 7, 17, and 20 showed inhibition on the expression of PI3K/Akt/NF-κB signaling pathway-related proteins. Additionally, it was noted in the pharmacodynamic experiment that ZJL's effectiveness was more apparent than ZJH and SQL in tumor burden rate, colon length, and spleen weight, which indicated that the efficacy of ZJ is contributed from CD and SQ, and they may have a synergistic effect on anti-CRC. Conclusion These results for the first time provide evidence that jujube triterpenes possess an anti-CRC effect, their mechanism was involving the control of the PI3K/Akt/NF-κB signaling pathway. What's more, the potential synergistic effect of the fat-soluble and water-soluble components found in this study provided a solid foundation for our deep understanding of how jujube can ameliorate CRC.
研究领域:
药理学
·
肿瘤学
·
分子生物学
·
中医药
✓ 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）