TOXICOLOGY
·
2025
·
IF 4.6
Liya Fang,Jinhua Xu,Chanlin Fang,Yuanxiang Jin
N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) is a commonly used rubber protectant that continuously enters the environment via groundwater. Its oxidation product, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPDQ), has garnered significant concern due to its reported toxicity in animals. This study aims to evaluate the intestinal toxicity and potential metabolic impact of 6PPD and 6PPDQ in mice following oral exposure to various doses. Our results demonstrate that both compounds compromise the intestinal barrier, as evidenced by significant increases in the expression of tight junction proteins (claudin-1 and occludin) and mucin protein (MUC2). These changes suggest an impairment of both the physical and chemical barriers of the intestine. Following exposure, there was a marked increase in pro-inflammatory cytokines (IL-6, IL-22, and NOD-1), indicating an inflammatory response associated with the disruption of lipid metabolism and macrophage polarization. Specifically, the shift from M2 to M1 macrophage polarization correlates with increased expression of M1 markers despite no change in the M1/M2 ratio over prolonged exposure. Furthermore, 6PPD exposure significantly reduced gut microbiota richness and evenness, with more pronounced changes observed in the 6PPDQ-treated group. Correlation analysis suggested that these microbial shifts may influence host carnitine and lipid metabolism pathways. Ultimately, both 6PPD and 6PPDQ exposure led to elevated levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) in the bloodstream, attributed to decreased TC esterification. These findings highlight the potential long-term health risks associated with environmental exposure to 6PPD and 6PPDQ, particularly concerning gut integrity and metabolic dysregulation. Synopsis This study investigates the toxicity of 6PPD and its transformation product 6PPDQ, revealing their detrimental effects on intestinal health, disruption of gut microbiota, and alterations in lipid metabolism, highlighting significant implications for both environmental and human health.
研究领域:
毒理学
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环境健康
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分子生物学
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代谢学
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微生物组学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Tianxiang Zhu,Baifei Hu,Cheng Ye,Haiming Hu,Mingzhu Yin,Zhigang Zhang,Shuiqing Li,Yanju Liu,Hongtao Liu
This study aimed to elucidate the mechanism of Bletilla striata oligosaccharides (BO) in the treatment of ulcerative colitis (UC). A UC mouse model was induced by 3% Dextran sodium sulfate (DSS), and BO (200 mg/kg/d) were administered for intervention. The results show that BO effectively inhibited the release of intestinal inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Also, BO profoundly elevated the secretion of mucins and the expression of tight junction (TJ) proteins to attenuate dysfunction of the intestinal barrier. The 16S rDNA sequencing and liquid chromatography/gas chromatography-mass spectrometer (LC/GC-MS) analysis of mouse feces revealed that BO regulated the disturbance of gut microbiota and intestinal metabolites. By using the in vitro fermentation broth of BO and gut microbiota-depleted mice treated with antibiotics, we confirmed the protection of BO against UC. In conclusion, BO played a role in improving UC by modulating gut microbial composition and intestinal metabolites, which provided new therapeutic strategies for UC treatment.Keywords:
Bletilla striata oligosaccharides, ulcerative colitis, gut microbiota, intestinal metabolites, intestinal barrier
研究领域:
药理学
·
胃肠病学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2024
·Vol. 13
·期 2
·153
·
IF 6
Zhaojun Chen,Hui Wang,Lulin Tan,Xiong Liu
Hydroxy-α-sanshool (HAS), hydroxy-β-sanshool (HBS), hydroxy-γ-sanshool (HRS), and γ-sanshool (RS) are the key components from theZanthoxylumgenus, processing a range of pharmacological activities. The present study investigated the protective capacities of four sanshools on a dextran sulfate sodium (DSS)-induced model of ulcerative colitis (UC). The results showed that sanshool administration alleviated the colitis symptoms by reducing body weight loss and disease activity index (DAI) score, increasing the colon length, and improving colonic injury and the change in immune organ weight. Furthermore, sanshools enhanced the antioxidant enzyme activities, and RS exhibited the lowest effect on the improvement in total antioxidative capacity (T-AOC) and antioxidant abilities compared to the other three sanshools. The p65 nuclear factor κB (p65 NFκB) signaling pathway was inhibited to prevent hyperactivation and decreased the production of inflammatory factors. The gut barrier function in DSS-induced mice was restored by increasing goblet cell number and levels of tight junction proteins (zonula occludens-1, occludin, and claudin-1), and the levels of protein in HAS and HRS groups were higher than that in the HBS group, significantly. The analysis of gut microbiota suggested that sanshool administration significantly boosted the abundance ofLachnospiraceae,Muribaculaceae,Oscillospiraceae, andAlistipesand reduced the level ofBuchnerain colitis mice. Collectively, the sanshool treatment could ameliorate colitis by resisting colon injury and regulating intestinal barrier dysfunction and gut microbiota dysbiosis; meanwhile, HRS and HAS have better improvement effects.Keywords:sanshool;colitis;intestinal barrier;p65;intestinal flora
研究领域:
药理学
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胃肠病学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Rili Hao,Xing Zhou,Xinyue Zhao,Xiaqing Lv,Xiangyang Zhu,NaNa Gao,Yang Jiang,Maoyu Wu,Dongxiao Sun-Waterhouse,Dapeng Li
Cadmium (Cd), as Group I carcinogen, can induce damage to various organs including the gut. It is of great importance to meet the rising demand for effective therapies against Cd-induced damage and investigate the mechanism. Flammulina velutipes is a popular edible mushroom, despite the well-known health benefits of Flammulina velutipes , little is known about the effect of its polysaccharide (FVP) against CdCl 2 -intestinal injury. In this study, a FVP (uronic acid, 5.10 %; degree of methylation, 41.24 %) was produced via hot water extraction (85 °C) and ethanol precipitation. The FVP contained eight major monosaccharides and exhibited good thermal stability at temperatures lower than 139.73 °C. FVP (100 mg/kg b. w., gavage for 4 weeks) alleviated CdCl 2 (1.5 mg/kg b. w., gavage for 4 weeks)-induced intestinal inflammation and apoptosis, intestinal permeability alteration and intestinal barrier disruption. FVP increased the abundance of Bacteroides , whilst decreasing the abundance of Desulfovibrionales and Clostridium . FVP also restored the levels of short-chain fatty acids (SCFAs), including acetic, propionic, isobutyric, butyric, isovaleric and valeric acids. Correlation analysis indicated the interplays among the FVP, gut microbes, SCFAs, intestinal barrier/cells and gut inflammation. FVP enhances the metabolic functions of gut microbiota via functional pathways analyzed by KEGG database. Furthermore, gut microbial transplantation of FVP + CdCl 2 group mice partially alleviated CdCl 2 caused-gut damage. Thus, FVP may be an effective therapeutic agent against CdCl 2 -induced gut damage via SCFA-mediated regulation of intestinal inflammation and gut microbiota-related energy metabolism. This study may open a new avenue for developing alternative strategies to prevent CdCl 2 -caused injury.
研究领域:
毒理学
·
药理学
·
微生物学
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营养学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2025
·
IF 4.2
Fang Wu,Yaqiong Liu,Ming Zhang,Xinlei Yuan,Yutong Jin,Yixuan Li,Ran Wang,Yanling Hao,Bing Fang
1,3-Dioleoyl-2-palmitoyl-glycerol (OPO) is a specific triglyceride in human breast milk, and it has been added to infant formula to mimic human breast milk fat. Existing studies only focused on its effects on fatty acid and calcium absorption, as well as the intestinal microbial composition; however, effects of OPO on the early-life development of intestine were still unclear. Our study explored the effects of OPO on intestinal epithelial structure and barrier construction in neonatal mice and the involvement of intestinal microorganisms. OPO supplementation significantly increased the number of intestinal stem cells, which in turn promoted villus and crypt, and promoted goblet cell and Paneth cell differentiation. OPO also promotes epithelial barrier integrity by increasing the expression of mucin 2, lysozyme 1, and tight junction proteins. Furthermore, the benefits of OPO were associated with the higher abundance of beneficial bacteria ( unclassified_f_Muribaculaceae , Akkermansia , Bifidobacterium , and Blautia ) and elevated butyrate levels. This study demonstrates the efficacy of OPO on intestinal health in neonatal mice beyond defecation, expands the understanding of the biological functions of OPO, and expands its application in intestinal health products targeting special populations, such as the elderly or individuals with intestinal fragility or injury.
研究领域:
营养学
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肠道健康
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
eFood
·
2025
·Vol. 6
·期 3
·e70058
·
IF 5.7
Shutong Chen,Bo Teng,Wancong Zhang,Jude Juventus Aweya,Kit-Leong Cheong
Morchella esculenta polysaccharides (MEPs) are known to have multiple bioactive properties, including immunomodulatory, anticancer, antioxidant, anti-inflammatory, etc. In this study, we assessed the impact of MEPs on dextran sulfate sodium (DSS)-induced colitis in mice, focusing on intestinal barrier and microbiota modulation. Using NMR analysis, MEPs were found to predominantly consist of 1,4,6- α - d -Glc p and 1,4- α - d -Glc p . MEPs were able to significantly alleviate weight loss, reduce colon length shortening, and mitigate colon pathology in mice. Notably, MEPs suppressed elevated pro-inflammatory cytokines levels but boosted anti-inflammatory cytokine levels. Besides, MEPs modulated gut microbiota, enhancing microbial diversity and promoting homeostasis compared to untreated. Furthermore, there was a higher relative abundance of beneficial bacteria, indicating that MEPs could enhance gut microbiota composition. Collectively, MEPs have promising therapeutic potential in preventing colitis, and therefore could be developed as a novel nutraceutical strategy.
研究领域:
营养学
·
免疫学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Fei Shen,Huiting Zhu,Zhongyan Bao,Di Han,Juan Du,Minjie Zhao,Fengqin Feng,Guanghua He,Qiufen Mo
Constipation is a common gastrointestinal condition. Lactiplantibacillus plantarum T34 has been demonstrated efficacy in relieving loperamide-induced constipation in mice model. Oral intervention of L. plantarum T34 (1 × 10 8 CFU/mouse/day) resulted in improved defecation and enhanced intestinal morphology. Mechanistic studies revealed that L. plantarum T34 strengthend the intestinal barrier through the upregulation of tight junction protein genes, specifically Claudin-1 , as well as mucosal barrier proteins such as Muc2 and Muc3 . Additionally, L. plantarum T34 modulated gut homeostasis by influencing the expression of aquaporin genes, levels of the gut neurotransmitter serotonin (5-HT), and oxidative stress markers. Furthermore, L. plantarum T34 effectively restored the composition of the gastrointestinal microbiota, addressing dysbiosis linked to constipation. These findings suggested that L. plantarum T34 may serve as a promising probiotic intervention for managing constipation, offering a safe and effective alternative to traditional treatments.
研究领域:
微生物学
·
消化系统疾病
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Mingwei Sun,Meng Zhao,Linlin Du,Jieying Hou,Juane Dong,Bin Zhang
Constipation is a prevalent intestinal disorder that significantly diminishes patients' quality of life and predisposes them to various serious health conditions. Current therapeutic approaches for constipation frequently result in drug dependence and adverse effects. In this study, we present evidence that licorice water extract (LWE), a naturally derived compound from Glycyrrhiza uralensis Fisch, effectively ameliorates constipation in mice induced by diphenoxylate (DIP). Our findings indicate that oral administration of LWE (82 mg/kg/d) substantially reduces defecation time, enhances intestinal motility, and increases fecal water content in constipated mice. Furthermore, LWE elevates the levels of excitatory neurotransmitters such as serotonin (5-HT) and motilin (MTL), while concurrently decreasing the levels of inhibitory neurotransmitters including vasoactive intestinal peptide (VIP), nitric oxide (NO) as well as Lipopolysaccharide (LPS). Mechanistically, compared to the model control group, the LWE treatment upregulates the expression of ZO-1, Occludin , and MUC2 genes; repairs DIP-induced damage to the intestinal barrier; increases aquaporin 3 ( AQP3 ) protein expression; downregulates Toll-like receptor 4 ( TLR4 ); mitigates low-grade intestinal inflammation; and restores colonic goblet cell populations. Additionally, LWE is metabolized by gut microbiota, thereby restoring dysbiosis associated with DIP-induced constipation. In conclusion, our results suggest that LWE alleviates constipation through mechanisms involving intestinal barrier repair and gut microbiota modulation, highlighting its potential as an alternative therapeutic option for this condition. In response to this, we have developed a convenient gel-type candy (LWEI) with licorice extract and inulin as the main ingredients, which has shown good efficacy in relieving constipation.
研究领域:
医学
·
生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Yi Zhao,Zi-Yan Hu,Ming Lou,Fu-Wei Jiang,Yi-Feng Huang,Ming-Shan Chen,Jia-Xin Wang,Shuo Liu,Yu-Sheng Shi,Hong-Mei Zhu,Jin-Long Li
Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.
研究领域:
毒理学
·
胃肠病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Yeye Hu,Yanting Wang,Haoyang Gao,Guigui Yang,Jing Xie,Ziliang He,Shenghui Lv,Fenglin Gu,Chaoqing Huang,Weicheng Hu
Inflammatory bowel disease (IBD) is a global health concern with limited therapeutic options. Previous studies have demonstrated that piperine exhibited anti-inflammatory effects both in vitro and in vivo. However, its potential to ameliorate colitis in mice through modulation of gut microbiota has not been explored. This study aimed to investigate the role of gut microbiota in the protective effects of piperine against colitis using a dextran sulfate sodium (DSS)-induced mouse model. Mice were administered piperine (12.5 and 25 mg/kg) prior to DSS exposure. Fecal microbiota transplantation (FMT) was then performed, after which we evaluated colitis symptoms, inflammation levels, and intestinal barrier function. Subsequently, 16S rDNA-based high-throughput sequencing was employed to analyze the microbial composition of the mouse cecal contents. Piperine administration increased the colon length, decreased the spleen index, and improved colon histopathology. Furthermore, piperine modulated inflammatory responses by inhibiting NF-κB signaling, thereby reducing the release of pro-inflammatory cytokines and mediators. It also enhanced intestinal barrier integrity by increasing the expression of claudin-1, claudin-3, ZO-1, occludin, and mucin 2. Notably, the 16S rDNA sequencing results revealed that piperine increased the abundance of Dubosiella in the gut. Piperine effectively protected mice from DSS-induced colitis, suppressed inflammation, and improved poor intestinal barrier function. It reshaped the intestinal microbiota, ultimately alleviating DSS-induced colitis in mice. Our research highlighted the significant role of gut microbiota in the piperine-mediated alleviation of intestinal damage and suggested its therapeutic potential for promoting gut health and reducing the risk of colitis.
研究领域:
医学
·
微生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2020
·
IF 3.225
Haisu Liu,Shengli Fu,Sanshan Zhang,Mingmei Ding,Anli Wang
Lead (Pb) is an environmental pollutant that can accumulate in fish and humans. In this study, the effects of juvenile bighead carp ( Hypophthalmichthys nobilis ) on the intestinal structure, gut microbiota and cell apoptosis in the intestine of juvenile bighead carp ( Hypophthalmichthys nobilis ) after 96 h of Pb exposure were detected. The results showed that the intestinal barrier was severely damaged, including intestinal leukocyte infiltration , goblet cells significantly increased, intestinal villi shortened significantly, and abnormal thickening of the intestinal wall. Meanwhile, the mRNA expressions of structure related genes ( villin-1 and Claudin-12 ) were down-regulated after Pb exposure, while pro-inflammatory factors ( IL-8 and TNF-α ) were up-regulated and peaked at 48 h. It shows that Pb causes intestinal inflammation and destroys intestinal structure. Furthermore, MiSeq sequencing data of the 16S rRNA gene V3-V4 region revealed a reduction in richness and diversity of intestine microbiota after Pb exposed. At the phylum level, the abundance of enteropathogenic bacteria ( Proteobacteria and Bacteroidetes ) were increased significantly whereas Firmicutes and Cyanobacteria were decreased significantly after exposed to Pb. A more in-depth analysis, at the genus level, a total of 40 intestinal microbes identified by operational taxonomic unit (OTU) analysis were obviously changed at 6 h, 48 h and 96 h after exposure to Pb, and the abundance of pathogenic bacteria such as Chryseobacterium also increased significantly. The functional prediction results of intestinal flora showed that the abundance of apoptosis was down-regulated after Pb exposure. It was consistent with the mRNA expressions of Bid , Caspase-2 , and Caspase-3 , indicating that apoptosis function of cells and intestinal flora was disturbed. Taken together, it is speculated that Pb may lead to the destruction of the intestinal barrier of bighead carp, leading to the disorder of the intestinal microbial community , which in turn promotes the occurrence of cell apoptosis. Our research provided some evidence for the association between microbiota dysbiosis and cell apoptosis after Pb exposure in the intestine of juvenile bighead carp.
研究领域:
环境科学
·
水生毒理学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 5
·4412
·
IF 5.6
Xinping Guo,Ziang Qian,Qiqi Pan,Yuqing Hu,Wangxin Mei,Xiumei Xing,Shaowu Yin,Jie Ji,Kai Zhang
Excessive use of antibiotics in aquaculture causes residues in aquatic animal products and harms human health. However, knowledge of florfenicol (FF) toxicology on gut health and microbiota and their resulting relationships in economic freshwater crustaceans is scarce. Here, we first investigated the influence of FF on the intestinal health of Chinese mitten crabs, and then explored the role of bacterial community in FF-induced intestinal antioxidation system and intestinal homeostasis dysbiosis. A total of 120 male crabs (48.5 ± 4.5 g) were experimentally treated in four different concentrations of FF (0, 0.5, 5 and 50 μg/L) for 14 days. Responses of antioxidant defenses and changes of gut microbiota were assessed in the intestine. Results revealed that FF exposure induced significant histological morphology variation. FF exposure also enhanced immune and apoptosis characteristics in the intestine after 7 days. Moreover, antioxidant enzyme catalase activities showed a similar pattern. The intestinal microbiota community was analyzed based on full-length 16S rRNA sequencing. Only the high concentration group showed a marked decrease in microbial diversity and change in its composition after 14 days of exposure. Relative abundance of beneficial genera increased on day 14. These findings illustrate that exposure to FF could cause intestinal dysfunction and gut microbiota dysbiosis in Chinese mitten crabs, which provides new insights into the relationship between gut health and gut microbiota in invertebrates following exposure to persistent antibiotics pollutants.Keywords:florfenicol;gut barrier;apoptosis;gut microbiota;crab
研究领域:
水产养殖
·
毒理学
·
微生物学
·
动物健康
✓ 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）