Advanced Science
·
2022
·Vol. 9
·期 16
·2104089
·
IF 17.521
Keli Yang,Xiaocheng Wang,Rongkang Huang,Hui Wang,Ping Lan,Yuanjin Zhao
Manipulation of gut microbiota by bacterial metabolites has shown protective effects against colitis; while the efficacy is strictly limited by the poor oral delivery efficiency and single drug usage. Here, a novel prebiotics and postbiotics synergistic delivery microcapsule composed of indole-3-propionic acid (IPA) postbiotic and three prebiotics including alginate sodium, resistant starch (RS), and chitosan via microfluidic electrospray for preventing and treating colitis are proposed. It is found that oral administration of IPA microcapsules (IPA@MC) to mice can exert significant protective effects to colitis, suggesting the therapeutic synergy between prebiotics and postbiotics. Furthermore, the mechanism of the IPA@MC is revealed in modulating the gut microbiota, that is by significantly increasing the overall richness and abundance of short-chain fatty acids (SCFA) producing bacteria such as Faecalibacterium and Roseburia . These results indicate that the prebiotics and postbiotics synergistic delivery microcapsules are ideal candidates for treating colitis.
研究领域:
生物工程
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医学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2022
·
IF 8.943
Jingyu Wang,Lin Han,Ziyan Liu,Wei Zhang,Lei Zhang,Jiaru Jing,Ai Gao
Benzene is a group I carcinogen determined by IARC. The prevalence of benzene in occupational and general environments increases the risk of acute myeloid leukemia (AML) among workers and childhood leukemia. However, the mechanism of hematotoxicity induced by benzene remains unclear. Recently, the gut microbiota has been regarded as a pivotal part of normal and malignant hematopoiesis . Therefore, in this study, we explored the function of gut microbiota in hematopoietic injury induced by benzene by 16S rRNA sequencing. We found that benzene exposure caused bone marrow damage, hematopoietic stem and progenitor cells ( HSPCs) dysfunction, and peripheral blood cell reduction. Moreover, intestinal barrier damage and gut microbiota dysbiosis were also observed in benzene-exposed mice. Interestingly, two gut flora, Lachnospiraceae_NK4A136_group and unclassified_Muribaculaceae, were significantly up-regulated and associated with hematopoietic indicators, suggesting that gut-host crosstalk might mediate benzene hematotoxicity. Microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), bile acids, and tryptophan metabolites, are the primary mediators of the gut-host crosstalk . Therefore, we conducted absolute quantitative metabolomics to investigate the impact of benzene exposure on these metabolites in mice. The results showed that the concentration of SCFA butyrate, t ryptophan metabolites kynurenine, and Indole-3-propionic acid (IPA) were significantly altered after benzene exposure. However, no difference was found in bile acids. Significant correlations were found between altered metabolites and hematopoietic indicators. We then investigated the flora that derived these metabolites. Lachnospiraceae_NK4A136_group and unclassified_Muribaculaceae were enriched in the butyrate metabolism and tryptophan metabolism pathways. Correlation analysis further suggested that unclassified_Muribaculaceae was positively associated with butyrate (r = 0.588, P < 0.05) and IPA (r = 0.59, P < 0.05). The above results demonstrated that unclassified_Muribaculaceae and microbiota-derived butyrate and IPA were involved in hematopoietic toxicity caused by benzene. This study provides insight into gut microbiota-derived metabolites-host crosstalk in benzene hematopoietic toxicity.
研究领域:
毒理学
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微生物组学
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血液学
✓ 已验证
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 12
·1878
·
IF 4.7
Yushi Wei,Dan Zhang,Junhui Pan,Deming Gong,Guowen Zhang
Indole-3-propionic acid (IPA) is a plant growth regulator with good specificity and long action. IPA may be harmful to human health because of its accumulation in vegetables and fruits. Therefore, in this study, the properties of the interaction between calf thymus DNA (ctDNA) and IPA were systematically explored using multispectroscopic and computational modeling approaches. Analysis of fluorescence spectra showed that IPA binding to ctDNA to spontaneously form a complex was mainly driven by hydrogen bonds and hydrophobic interaction. DNA melting analysis, viscosity analysis, DNA cleavage study, and circular dichroism measurement revealed the groove binding of IPA to ctDNA and showed that the binding did not significantly change ctDNA confirmation. Furthermore, molecular docking found that IPA attached in the A-T rich minor groove region of the DNA. Molecular dynamics simulation showed that DNA and IPA formed a stable complex and IPA caused slight fluctuations for the residues at the binding site. Gel electrophoresis experiments showed that IPA did not significantly disrupt the DNA structure. These findings may provide useful information on the potential toxicological effects and environmental risk assessments of IPA residue in food at the molecular level.
研究领域:
生物化学
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分子生物学
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计算生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-22
·
IF 12.6
Yang Chuan,Xie Langlang,Deng Zihan,Ai Hongbo,Xiang Tingwen,Yan Xiaojing,Ling Zhiguo,Xiao Shiyu,Tang Yong,Huang Gang,Luo Fei,Chen Yueqi
Dysbiosis of gut microbiota significantly exacerbates the progression of rheumatoid arthritis (RA). Targeting gut microbiota may present a promising therapeutic strategy for RA. Gold nanospheres (GNS), known for excellent biocompatibility, stability and minimal toxicity, have emerged as precise modulators of gut microbiota, reshaping intestinal environments to treat various inflammatory diseases. Our study found that oral administration of 60-nm GNS effectively ameliorated collagen-induced arthritis (CIA) in mice, with a marked reduction in disease severity and synovial inflammation. Specifically, GNS notably enriched the probiotic genus Ligilactobacillus while restoring intestinal barrier function by upregulating tight junction proteins Claudin-1 and ZO-1. Targeted metabolomics analysis revealed GNS substantially increased the production of indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA) in gut, which were shown to activate the aryl hydrocarbon receptor (AhR) pathway. Mechanistic studies demonstrated that the IPA/IAA mixture inhibited PTEN ubiquitination, stabilizing PTEN protein levels and suppressing NF-κB activation in synovial tissues. These changes correlated with reduced synovial hyperplasia and inflammatory infiltration. Our findings established GNS as an effective nanomodulator of the gut-joint axis, providing novel insights into microbiota-targeted therapies for RA and other inflammatory diseases. Graphical abstract
研究领域:
医学
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免疫学
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微生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Gut Microbes
·
2024
·
IF 12.2
Jiyan Su,Xiaojie Lin,Dan Li,Chunmin Yang,Shumei Lv,Xiaohong Chen,Xiujuan Yang,Botao Pan,Rui Xu,Liping Ren,Yanfang Zhang,Yizhen Xie,Qianjun Chen,Chenglai Xia
Emerging evidence has revealed the novel role of gut microbiota in the development of cancer. The characteristics of function and composition in the gut microbiota of patients with breast cancer patients has been reported, however the detailed causation between gut microbiota and breast cancer remains uncertain. In the present study, 16S rRNA sequencing revealed that Prevotella, particularly the dominant species Prevotella copri, is significantly enriched and prevalent in gut microbiota of breast cancer patients. Prior-oral administration of P. copri could promote breast cancer growth in specific pathogen-free mice and germ-free mice, accompanied with sharp reduction of indole-3-pyruvic acid (IPyA). Mechanistically, the present of excessive P. copri consumed a large amount of tryptophan (Trp), thus hampering the physiological accumulation of IPyA in the host. Our results revealed that IPyA is an intrinsic anti-cancer reagent in the host at physiological level. Briefly, IPyA directly suppressed the transcription of UHRF1, following by the declined UHRF1 and PP2A C in nucleus, thus inhibiting the phosphorylation of AMPK, which is just opposite to the cancer promoting effect of P. copri. Therefore, the exhaustion of IPyA by excessive P. copri strengthens the UHRF1-mediated negative control to inactivated the energy-controlling AMPK signaling pathway to promote tumor growth, which was indicated by the alternation in pattern of protein expression and DNA methylation. Our findings, for the first time, highlighted P. copri as a risk factor for the progression of breast cancer.
研究领域:
癌症生物学
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微生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2024
·Vol. 30
·期 4
·1-10
·
IF 3.4
Ying Chen,Yu Li,Xiaojuan Li,Qingqing Fang,Feng Li,Shiyao Chen,Weichang Chen
Indole‑3‑propionic acid (IPA), a product of Clostridium sporogenes metabolism, has been shown to improve intestinal barrier function. In the present study, in vitro experiments using NCM460 human colonic epithelial cells were performed to investigate how IPA alleviates lipopolysaccharide (LPS)‑induced intestinal epithelial cell injury, with the aim of improving intestinal barrier function. In addition, the underlying mechanism was explored. NCM460 cell viability and apoptosis were measured using the Cell Counting Kit‑8 assay and flow cytometry, respectively. The integrity of the intestinal epithelial barrier was evaluated by measuring transepithelial electrical resistance (TEER). The underlying molecular mechanism was explored using western blotting, immunofluorescence staining, a dual luciferase reporter gene assay and quantitative PCR. The results showed that 10 µg/ml LPS induced the most prominent decrease in cell viability after 24 h of treatment. By contrast, IPA effectively inhibited LPS‑induced apoptosis in the intestinal epithelial cells. Additionally, >0.5 mM IPA improved intestinal barrier function by increasing TEER and upregulating the expression of tight junction proteins (zonula occludens‑1, claudin‑1 and occludin). Furthermore, IPA inhibited the release of pro‑inflammatory cytokines (IL‑1β, IL‑6 and TNF‑α) in a dose‑dependent manner and this was achieved via regulation of the Toll‑like receptor 4 (TLR4)/myeloid differentiation factor 88/NF‑κB and TLR4/TRIF/NF‑κB pathways. In conclusion, IPA may alleviate LPS‑induced inflammatory injury in human colonic epithelial cells. Taken together, these results suggest that IPA may be a potential therapeutic approach for the management of diseases characterized by LPS‑induced intestinal epithelial cell injury and intestinal barrier dysfunction.
研究领域:
胃肠病学
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免疫学
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细胞生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
ANTIOXIDANTS & REDOX SIGNALING
·
2023
·
IF 6.6
Dr. Jiedong Zhou,Dr. Jinjin Hao,Dr. Zuoquan Zhong,Dr. Juntao Yang,Dr. Tingting Lv,Mr. Bingjie Zhao,Dr. Hui Lin,Dr. Jufang Chi,Dr. Hangyuan Guo
Aims: The relationship between gut microbiota and cardiovascular system has been increasingly clarified. Fecal microbiota transplantation (FMT), used to improve gut microbiota, has been applied clinically for disease treatment and has great potential in combatting doxorubicin (DOX)-induced cardiotoxicity. However, the application of FMT in the cardiovascular field and its molecular mechanisms are poorly understood.
Results: During DOX-induced stress, FMT alters the gut microbiota and serum metabolites, leading to a reduction in cardiac injury. Correlation analysis indicated a close association between serum metabolite Indole-3-propionic acid (IPA) and cardiac function. FMT and IPA achieves this by facilitating the translocation of Nfe2l2 (Nrf2) from the cytoplasm to the nucleus, thereby activating the expression of antioxidant molecules, reducing ROS production, and inhibiting excessive mitochondrial fission. Consequently, mitochondrial function is preserved, leading to the mitigation of cardiac injury under DOX-induced stress.
Innovation: FMT has the ability to modify the composition of the gut microbiota, providing not only protection to the intestinal mucosa but also influencing the generation of serum metabolites and regulating the Nrf2 gene to modulate the balance of cardiac mitochondrial fission and fusion. This study comprehensively demonstrates the efficacy of FMT in countering DOX-induced myocardial damage and elucidates the pathways linking the microbiota and the heart.
Conclusion: FMT alters the gut microbiota and serum metabolites of recipient mice, promoting nuclear translocation of Nrf2 and subsequent activation of downstream antioxidant molecule expression, while inhibiting excessive mitochondrial fission to preserve cardiac integrity. Correlation analysis highlights IPA as a key contributor among differentially regulated metabolites.
研究领域:
心脏病学
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药理学
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微生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xinru Huang,Shaoping Nie,Xiaodan Fu,Shihao Nan,Xinmiao Ren,Rong Li
Fucoidan is widely applied in food and pharmaceutical industry for the promising bioactivities. Low-molecular weight hydrolyzed fucoidan has gained attention for its beneficial health effects. Here, the modulation on microbiome and metabolome features of fucoidan and its acidolyzed derivatives (HMAF, 1.5–20 kDa; LMAF, <1.5 kDa) were investigated through human fecal cultures. Fucose is the main monosaccharide component in fucoidan and LMAF, while HMAF contains abundant glucuronic acid. LMAF fermentation resulted in the highest production of short-chain fatty acids, with acetate and propionate reaching maximum levels of 13.46 mmol/L and 11.57 mmol/L, respectively. Conversely, HMAF exhibited a maximum butyrate production of 9.28 mmol/L. Both fucoidan and acidolyzed derivatives decreased the abundance of Escherichia-Shigella and Klebsiella in human fecal cultures. Fucoidan and HMAF prefer to improve the abundance of Bacteroides . However, LMAF showed positive influence on Bifidobacterium , Lactobacillus , and Megamonas . Untargeted metabolome indicated that fucoidan and its derivatives mainly altered the metabolic level of lipids, indole, and their derivatives, with fucoidan and HMAF promoting higher level of indole-3-propionic acid and indole-3-carboxaldehyde compared to LMAF. Considering the chemical structural differences, this study suggested that hydrolyzed fucoidan can provide potential therapeutic applications for targeted regulation of microbial communities.
研究领域:
食品科学
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药学
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微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Jiaojiao Li,Li Zhang,Tao Wu,Yafei Li,Xiaojun Zhou,Zheng Ruan
Destruction in intestinal barrier is concomitant with the intestinal diseases. There is growing evidence that tryptophan-derived intestinal bacterial metabolites play a critical role in maintaining the balance of intestinal mucosa. In this study, the Caco-2/HT29 coculture model was used to evaluate the effect of indole-3-propionic acid (IPA) on the intestinal barrier and explore its underlying mechanism. We found that IPA increased transepithelial electrical resistance and decreased paracellular permeability which was consistent with the increase in tight junction proteins (claudin-1, occludin, and ZO-1). Furthermore, IPA strengthened the mucus barrier by increasing mucins (MUC2 and MUC4) and goblet cell secretion products (TFF3 and RELMβ). Additionally, IPA weakened the expression of LPS-induced inflammatory factors. These discoveries provide new views for understanding the improvement of intestinal barrier by gut microbial metabolites of aromatic amino acids.
研究领域:
胃肠病学
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微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2024
·
IF 3.3
Yanxi Dong,Jiali Dong,Huiwen Xiao,Yuan Li,Bin Wang,Shuqin Zhang,Ming Cui
BACKGROUND Excessive body weight and obesity elevate the risk of chronic non-communicable diseases. The judicious application of the gut microbiome, encompassing both microorganisms and their derived compounds, holds considerable promise in the treatment of obesity. RESULTS In this study, we showed that a cocktail of gut microbiota-derived metabolites, comprising indole 3-propionic acid (IPA), sodium butyrate (SB) and valeric acid (VA), alleviated various symptoms of obesity in both male and female mice subjected to a high-fat diet (HFD). The 16S ribosomal RNA (rRNA) sequencing revealed that administering the cocktail via oral gavage retained the gut microbiota composition in obese mice. Fecal microbiota transplantation using cocktail-treated mice as donors mitigated the obesity phenotype of HFD-fed mice. Transcriptomic sequencing analysis showed that the cocktail preserved the gene expression profile of hepatic tissues in obese mice, especially up-regulated the expression level of leptin receptor. Gene delivery via in vivo fluid dynamics further validated that the anti-obesity efficacy of the cocktail was dependent on leptin signaling at least partly. The cocktail also inhibited the expression of appetite stimulators in hypothalamus. Together, the metabolite cocktail combated adiposity by retaining the gut microbiota configuration and activating the hepatic leptin signaling pathway. CONCLUSIONS Our findings provide a sophisticated regulatory network between the gut microbiome and host, and highlight a cocktail of gut microbiota-derived metabolites, including IPA, SB, and VA, might be a prospective intervention for anti-obesity in a preclinical setting. © 2024 Society of Chemical Industry.
研究领域:
微生物学
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营养学
·
代谢组学
·
分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Science China-Life Sciences
·
2025
·
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
·
微生物学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Xinyuan Yang,Weimin Nie,Chong Wang,Zhonglin Fang,Luoran Shang
Probiotic-based therapies have shown great potential in the prevention and treatment of many diseases by positively regulating intestinal flora homeostasis. However, the efficacy of oral probiotics is severely limited due to the loss of bioactivity, short intestinal retention time, and insufficient therapeutic effect. Here, based on droplet microfluidics, we developed a hydrogel microsphere with colonic targeting and mucoadhesive capabilities as a multifunctional delivery platform, which can be used for co-delivery of probiotics ( Escherichia coli Nissle 1917, EcN) and auxiliary molecules (indole-3-propionic acid, IPA), achieving synergistic therapeutic effects. In vivo studies shown that the integrated multifunctional microspheres can significantly reduce intestinal inflammation, repair intestinal barrier function, enhance probiotic colonization in the intestine, and modulate disordered intestinal flora, demonstrating enhanced therapeutic effects in a mouse model of colitis. This work reveals that microfluidic-based smart droplet microspheres can provide a versatile platform for advanced microbial therapies.
研究领域:
药学
·
生物技术
·
微生物学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）