Frontiers in Endocrinology
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2025
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IF 4.6
Yating Xu,Li Ning,Yu Si,Xiu Li,Ruyue Wang,Qingling Ren
Introduction: Polycystic ovary syndrome (PCOS) is a complex disorder characterized by metabolic and ovulatory dysfunctions, often associated with an imbalance in gut microbiota. Despite current treatments, effective management strategies targeting underlying mechanisms remain limited.Methods: In this study, we used a rat model of PCOS induced by letrozole and a high-fat diet. The effect of intestinal AMP-activated protein kinase (AMPK) activation was evaluated through metformin administration, the most commonly used AMPK activator. We analyzed metabolic parameters, ovulatory functions, gut microbiota composition, and serum levels of Indole-3-carboxaldehyde (I3A), a metabolite involved in inflammation and apoptosis regulation.Results: Metformin treatment significantly reversed metabolic disorders and restored ovulatory functions in PCOS rats. Moreover, metformin treatment led to notable improvements in gut microbiota composition and an increase in serum I3A levels, which have been shown to mitigate inflammation and apoptosis.Discussion: This study highlights the therapeutic potential of targeting intestinal AMPK in managing PCOS. By improving both metabolic and reproductive health, activation of AMPK may offer a promising approach for restoring physiological balance in PCOS patients.
研究领域:
生殖医学
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代谢生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
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IF 2.5
Xinlei Liu,Rui Liu,Yancheng Wang
Drug-induced liver injury (DILI) occurs frequently and can be life-threatening. Increasing researches suggest that acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury. Indole-3-carboxaldehyde (I3A) alleviates hepatic inflammation, fibrosis and atherosclerosis, suggesting a potential role in different disease development. However, the question of whether and how I3A protects against acetaminophen-induced liver injury remains unanswered. In this study, we demonstrated that I3A treatment effectively mitigates acetaminophen-induced liver injury. Serum alanine/aspartate aminotransferases (ALT/AST), liver malondialdehyde (MDA) activity, liver glutathione (GSH), and superoxide dismutase (SOD) levels confirmed the protective effect of I3A against APAP-induced liver injury. Liver histological examination provided further evidence of I3A-induced protection. Mechanistically, I3A reduced the expression of apoptosis-related factors and oxidative stress, alleviating disease symptoms. Finally, I3A treatment improved survival in mice receiving a lethal dose of APAP. In conclusion, our study demonstrates that I3A modulates hepatotoxicity and can be used as a potential therapeutic agent for DILI.
研究领域:
药理学
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毒理学
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肝病学
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DOI
PubMed
高影响因子
GENOME BIOLOGY
·
2024
·Vol. 25
·期 1
·1-26
·
IF 10.1
Sun Daming,Bian Gaorui,Zhang Kai,Liu Ning,Yin Yuyang,Hou Yuanlong,Xie Fei,Zhu Weiyun,Mao Shengyong,Liu Junhua
Background The function of diverse ruminal microbes is tightly linked to rumen development and host physiology. The system of ruminal microbes is an excellent model to clarify the fundamental ecological relationships among complex nutrient–microbiome–host interactions. Here, neonatal lambs are introduced to different dietary regimes to investigate the influences of early-life crosstalk between nutrients and microbiome on rumen development. Results We find starchy corn-soybean starter-fed lambs exhibit the thickest ruminal epithelia and fiber-rich alfalfa hay-fed lambs have the thickest rumen muscle. Metabolome and metagenome data reveal that indole-3-carboxaldehyde (3-IAld) and prostaglandin D2 (PGD2) are the top characteristic ruminal metabolites associated with ruminal epithelial and muscular development, which depend on the enhanced ruminal microbial synthesis potential of 3-IAld and PGD2. Moreover, microbial culture experiment first demonstrates that Bifidobacterium pseudolongum is able to convert tryptophan into 3-IAld and Candida albicans is a key producer for PGD2. Transcriptome sequencing of the ruminal epithelia and smooth muscle shows that ruminal epithelial and muscular development is accompanied by Wnt and Ca 2+ signaling pathway activation. Primary cell cultures further confirm that 3-IAld promotes ruminal epithelial cell proliferation depending on AhR-wnt/β-catenin signaling pathway and PGD2 accelerates ruminal smooth muscle cell proliferation via Ca 2+ signaling pathway. Furthermore, we find that 3-IAld and PGD2 infusion promote ruminal epithelial and musculature development in lambs. Conclusions This study demonstrates that early-life ruminal microbiome-derived 3-IAld and PGD2 are effective promoters of rumen development, which enhances our understanding of nutrient–microbiome–host interactions in early life.
研究领域:
动物科学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Animal Science and Biotechnology
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2026
·Vol. 17
·期 1
·169
·
IF 7.9
Li Jiahao,Wang Zhengli,Ma Xiaoxue,Nie Cunxi,Liu Tingting,Li Yuanyuan,Zhang Wenju
Background Diarrhea in suckling lambs is associated with gut microbiota dysbiosis, impaired intestinal barrier function, and enhanced inflammatory responses. However, the specific intestinal microbes and microbial metabolites linked to intestinal homeostasis in suckling lambs remain unclear. Results In this study, diarrheic lambs showed significantly higher serum diamine oxidase (DAO) activity, D-lactate (D-LA), and pro-inflammatory cytokine levels than healthy lambs. We then compared gut microbial composition and metabolite profiles between healthy and diarrheic suckling lambs. Diarrheal lambs exhibited gut microbiota dysbiosis, characterized by an elevated Bacillota (syn. Firmicutes)/Bacteroidota (syn. Bacteroidetes) ratio, reduced abundance of beneficial commensals including Phocaeicola vulgatus and Bacteroides fragilis , and proliferation of the opportunistic pathogen Clostridium perfringens . Metabolomic analysis showed that, in diarrheic lambs, the tryptophan metabolism pathway was reduced with lower levels of indole-3-carboxaldehyde (IAld) and 5-hydroxyindole-3-acetic acid (5-HIAA) than in healthy lambs. Fecal microbiota transplantation experiments showed that transplantation of microbiota from diarrheic lambs partially recapitulated the donor-associated microbial, metabolic, and inflammatory phenotypes in recipient mice. Finally, functional validation using a dextran sulfate sodium (DSS)-induced colitis model revealed that supplementation with IAld and 5-HIAA significantly alleviated DSS-induced intestinal inflammation and barrier damage, accompanied by downregulated expression of genes related to the Tlr4-Myd88-Nfκb signaling pathway. Conclusions Our findings indicate that the gut microbiota-derived tryptophan metabolites IAld and 5-HIAA alleviated inflammation and improved intestinal epithelial barrier function by enhancing tight junction integrity, while also reducing the expression of Tlr4/Myd88/Nfκb pathway-related inflammatory signaling molecules.
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DOI
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Zhang Junzhi,Lin Binyan,Zhang Ying,Hu Xiaochao,Liu Tongtong,Liu E-Hu,Liu Shijia
Background: Baitouweng decoction (BTW) is a classic botanical drugs formula that has been widely used clinically for the treatment of gut-related disorders in China. However, its role in ameliorating ulcerative colitis (UC) remains to be explored.Purpose: The study aimed to determine the therapeutic efficacy and potential mechanism of action of BTW on dextran sodium sulfate (DSS)-induced colitis mice.Methods: In vivo: 3.5% DSS-induced experimental colitis mice were treated with BTW (Pulsatilla chinensis (Bunge) Regel, Phellodendron chinense C. K. Schneid, Coptis chinensis Franch and Fraxinus chinensis Roxb), kynurenine or DOPA decarboxylase (DDC) inhibitor (carbidopa). In vitro: Caco-2 cells were stimulated with TNF-α to activate inflammation and later treated with various concentrations of BTW and carbidopa. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Cytokine levels were measured by flow cytometry. Protein levels were analyzed by proteomics and functionally annotated. The levels of tryptophan metabolites in mouse serum and colon were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Alcian Blue/Phosphate Acid Schiff (AB/PAS) staining, immunohistochemistry and western blot were used to assess the intestinal barrier function and detect the protein expression levels.Results: BTW significantly reduced the DAI, ameliorated colonic injury and regulated inflammatory cytokines in DSS-induced colitis mice. The botanical drugs formula also promoted intestinal epithelial barrier repair by enhancing the expression of the tight junction (TJ) proteins. Tryptophan metabolic signaling pathway was significantly enriched in DSS-induced UC mice, and BTW decreased the level of kynurenine, increased indole metabolites. The therapeutic effect of BTW was evidently reduced when kynurenine was given to mice. Also, BTW promoted DDC protein expression and activated the aryl hydrocarbon receptor (AHR)/IL-22 signaling pathway.Conclusion: BTW improves ulcerative colitis by promoting DDC expression, regulating the conversion of tryptophan metabolism from the kynurenine pathway to the indole metabolism pathway, thereby modulating tryptophan metabolism to increase indole metabolites, and activating AHR receptors to restore intestinal barrier function.
研究领域:
药理学
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胃肠病学
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免疫学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Science China-Life Sciences
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2025
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IF 9.5
Han Ziyi,Fu Jian,Gong Aiyan,Ren Wenkai
The gut microbiota plays key roles in host health by shaping the host immune responses through their metabolites, like indole derivatives from tryptophan. However, the direct role of these indole derivatives in macrophage fate decision and the underlying mechanism remains unknown. Here, we found that bacterial indole-3-propionic acid (IPA) downregulates interleukin-1beta (IL-1β) production in M1 macrophages through inhibition of nuclear factor-kappa B (NF-κB) signaling. Mechanistically, IPA binds specifically with methionine adenosyl-transferase 2A (MAT2A) to promote S-adenosylmethionine (SAM) synthesis, which facilitates the DNA methylation of ubiquitin-specific peptidase 16 (USP16, a deubiquitinase), and in turn promotes Toll-like receptor 4 (TLR4) ubiquitination and NF-κB inhibition. Furthermore, IPA administration attenuates sepsis in mouse models induced by lipopolysaccharides (LPS), showcasing its potential as a microbial-derived adjunct in alleviating inflammation. Collectively, our findings reveal a newly found microbial metabolite-immune system regulatory pathway mediated by IPA.
研究领域:
免疫学
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微生物学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
POLYMER
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2024
·
IF 4.1
Yewei Xu,Haoran Zhu,Shijie Mo,Yangqing Mao,Chi Zhong,Ying Huang,Rui Yuan,Min Zheng,Mingru Zhou,Guanjun Chang
An indole-based porous organic polymer (PTIM) with antibacterial activity was prepared by Friedel-Crafts alkylation and supercritical drying from the self-made tri(1H-indol-3-yl)methane (TIM). The adsorption of 2,4,6-trinitrotoluene (TNT) by PTIM involved physisorption followed by chemisorption, and the mechanism was verified by theoretical simulation and experiment. The physisorption and chemisorption between PTIM and TNT as well as the suitable three-dimensional space size of cross-linked network in PTIM enabled PTIM to have an unprecedented adsorption capacity for TNT (399.2 mg/g). Meanwhile, the removal efficiency of PTIM for TNT was also very high, and it could reach more than 85% of the maximum adsorption capacity after only 1 h of adsorption. Furthermore, the adsorption capacity of PTIM to TNT in actual water samples was slightly less than that in the laboratory, while the adsorption equilibrium time (4 h) was much shorter than the laboratory data (13.75 h). As a result, PTIM could not only achieve primary purification of TNT wastewater from high concentration to low concentration, but also advanced purification from low concentration to standard discharge concentration. In addition, PTIM possessed excellent recycling performance, and the maximum adsorption capacity was still 97% of the initial capacity after five adsorption-desorption cycles Unexpectedly, PTIM also had good antibacterial activity, preventing bacteria from adhering to or covering the pores, and ensuring excellent adsorption capacity and recycling performance. These results showed that PTIM was a promising TNT adsorbent.
研究领域:
环境科学
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材料科学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Susu Zhao,Lixin Sun,Yibo Liu,Chuanhui Gao,Li Ding,Ze Kan,Yuetao Liu
Due to the limited static antifouling properties of silicone materials, their application in the marine field has been restricted. Chemical grafting antifouling agents onto matrix is an effective approach to enhancing this ability. Indole and its derivatives have garnered significant attention in marine antifouling due to their antibacterial, anti-UV and fluorescence properties. In this study, indole groups were introduced into the side chain of siloxane, and a novel silicone material was constructed utilizing cation-indole supramolecular interactions for the first time. As the constructed non-covalent cross-linked network, the maximum stress of materials could reach to 1.0 MPa, and the strain was up to 200 %. Furthermore, the materials exhibited self-healing capabilities at 60℃ for 9 h with a healing efficiency of 99 %, and could be fully recovered by solvent and hot pressing. As the coating materials, they effectively shielded ultraviolet light while maintaining a transmittance of 80 % in the visible region. The presence of indolyl group contributed to an inhibition rate 97.59 % against Escherichia coli and 93.75 % against Staphylococcus aureus. Additionally, the materials achieved a synergistic antifouling mechanism combining fluorescence and contact antibacterial effects. This study provided a new method for constructing silicone materials with potential applications in marine antifouling.
研究领域:
材料科学
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海洋生物学
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抗菌研究
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产品关联
DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Mengshi Xiao,Jiayuan Bi,Xinmiao Ren,Xiaodan Fu,Dongyu Li,Rong Li,Haijin Mou
Fucose-containing oligosaccharides exhibit various biological activities, particularly for improving the intestinal health of infants. Bacterial exopolysaccharides are promising resource of fucose-containing oligosaccharides. A fucose-containing trisaccharide ( d - Glc p-β-(1 → 4)- l - Fuc p and d - Gal p-α-(1 → 3)- l - Fuc p, GuFGa) with same monosaccharide composition with 2′-fucosyllactose (2′-FL, the most abundant oligosaccharide in human milk), is obtained from bacterial exopolysaccharides. This study compared the in vitro prebiotic activities of GuFGa and 2′-FL using mono- and co-culture fermentation. Mono-culture shows GuFGa could be utilized by Bifidobacterium infantis and Lactobacillus plantarum , while 2′-FL only promote the proliferation of B . infantis . Co-culture fermentation involves cross-feeding between B . infantis and L . plantarum to utilize GuFGa. Further in vitro fecal microbiota fermentation of breastfed infants demonstrates that GuFGa exhibits better prebiotic activity than 2′-FL in increasing beneficial bacteria ( Bifidobacterium and Lactobacillus ) abundance and reducing harmful bacteria ( Clostridium _ sensu _ stricto and Escherichia - Shigella ) abundance. Moreover, GuFGa and 2′-FL fermentation shifted the gut microbiota composition of formula-fed infants to that of breastfed infants. Furthermore, herein, GuFGa and 2′-FL caused distinct metabolic profiles in both short-chain fatty acids and indole derivatives (e.g. indolelactic acid and indolepropionic acid). In summary, this study provides insights into the exploration of novel functional fucose-containing oligosaccharides as potential prebiotics.
研究领域:
微生物学
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营养学
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胃肠病学
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产品关联
DOI
高影响因子
Food Chemistry-X
·
2024
·
IF 6.5
Jia Cheng Qian,Heng Peng Zhang,Yi Wang,Dan Liu
Cruciferous vegetables (CVs) are globally consumed with some health benefits believed to arise from indole-3-carbinol (I3C), a labile phytochemical liberated from indole glucosinolates, but few reports describe the effect of cooking on I3C reactions. Here, we present heat-promoted direct conversions of I3C in broccoli florets into indole derivatives, which are unique in the N -indolylmethylation and -hydroxymethylation of indole nuclei by 3-methyleneindole and formaldehyde formed in situ from the I3C dehydration and the dimerization of I3C to 3,3′-diindolylmethane (DIM), respectively. Such N -substituted indoles were found in a range of 0.4–4.6 μg per gram of steamed broccoli florets, with a novel compound N -(indol-3-ylmethyl)-3,3′-diindolylmethane (DIM-1) bio-evaluated to inhibit A375 cells with an IC 50 value of 1.87 μM. In aggregation, the investigation discloses the promoting effect of heating on the I3C transformation in CVs and identifies DIM-1 as an anti-cancer drug candidate, and thus updates the knowledge of I3C and bioactive derivatives thereof.
研究领域:
生物化学
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药理学
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癌症研究
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食品科学
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产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2024
·
IF 3.7
Yvhao Xie,Xinxin Li,Qingshi Meng,Jinjun Li,Xin Wang,Liying Zhu,Weiwei Wang,Xiaoqiong Li
Tryptophan (TRP) metabolites have been identified as potent biomarkers for complications of type 2 diabetes mellitus (T2DM). However, it remains unclear whether the therapeutic effect of metformin in T2DM is related to the modulation of TRP metabolic pathway. This study aims to investigate whether metformin affects TRP metabolism in T2DM mice through the gut microbiota. A liquid chromatography-tandem mass spectrometry method was established to determine 16 TRP metabolites in the serum, colon content, urine, and feces of T2DM mice, and the correlations between metabolites and the T2DM mice gut microbiota were performed. The method demonstrated acceptable linearity (R2 > 0.996), with the limit of quantification ranging from 0.29 to 69.444 nmol/L for 16 analytes, and the limit of detection ranging from 0.087 to 20.833 nmol/L. In T2DM mice, metformin treatment effectively restored levels of indole-3-lactic acid (ILA), indole-3-propionic acid (IPA), and the ILA/IPA ratio, along with several aryl hydrocarbon receptor ligands in the serum, with a notable impact in the colon but not in the urine. This restoration was accompanied by a shift in the relative abundance of Dubosiella, Turicibacter, RF39, Clostridia_UCG-014, and Alistipes. Spearman’s correlation analysis revealed positive correlations between Turicibacter and Alistipes with IPA and indole-3-acetic acid. Conversely, these genera displayed negative correlations with ILA and kynurenine. In addition, our study revealed the presence of endogenous indole pathway in germ-free mice, and the impact of metformin on endogenous TRP metabolism in T2DM mice cannot be disregarded. Further research is needed to investigate the regulation of TRP metabolism by metformin.
研究领域:
药理学
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微生物学
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代谢组学
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糖尿病研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2025
·
IF 6.4
Yufei Deng,Xiaoying Hou,Qian Fang,Haiping Wang,Xiaoxuan Li,Zhiyong Hu,Zhaolu Liu,Limei Fan,Yunyi Liu,Zhengqi Fu,Xiji Shu,Binlian Sun,Lijun Huang,Yuchen Liu
Background FOLFOX is the recommended chemotherapy regimen for colorectal cancer (CRC), but its response rate remains low. Our previous studies have established a close relationship between gut microbiota and the anti-CRC effect of FOLFOX, though the underlying mechanisms remain unclear. Diet has been confirmed as a key factor influencing gut microbiota, and high-salt diets, representative of western dietary habits, has been shown to affect gut microbiota, immune function, and the risk of developing CRC. However, the impact of high-salt diets on the anti-CRC efficacy of FOLFOX remains unstudied. Therefore, we aimed to investigate the effect and mechanism of high-salt diets on the anti-CRC effect of FOLFOX. Methods We performed 16 S rRNA sequencing and T500 targeted metabolomics analysis on fecal samples from CRC patients and healthy adults. A CRC orthotopic xenograft mouse model was used to study the effect of a high-salt diet on FOLFOX’s anti-CRC efficacy. 16 S rRNA sequencing and non-targeted metabolomics were conducted on mouse fecal samples. Flow cytometry was used to assess immune cell infiltration in tumor and paracancerous tissues. A mouse macrophage conditioned medium system, with tryptophan metabolites, was employed to annotate the functional metabolites, followed by in vivo verification using the orthotopic xenograft mouse model. Results The structure and metabolic profiles of gut microbiota are significantly different between 9 healthy adults and 6 CRC patients. A high-salt diet significantly reduced the efficacy of FOLFOX in mice, with notable changes in gut microbiota and related metabolites. Correlation analysis revealed a significant relationship between gut microbiota, tryptophan metabolites and FOLFOX efficacy. Flow cytometry indicated that a high-salt diet altered macrophage infiltration (CD45 + F4/80 + ) in both the tumor and paracancerous tissues. In vitro experiments confirmed that the tryptophan metabolite SK reduced FOLFOX efficacy, while IPA enhanced it through macrophage-conditioned medium. In vivo, we verified that under a high-salt diet, SK inhibited the efficacy of FOLFOX, while IPA promoted it. Conclusion A high-salt diet reduces the anti-CRC efficacy of FOLFOX through gut bacterial tryptophan metabolism mediated macrophage immunomodulation. Supplementary Information The online version contains supplementary material available at 10.1186/s10020-025-01122-8.
研究领域:
肿瘤学
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微生物学
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免疫学
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代谢组学
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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）