ACS Applied Materials & Interfaces
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2025
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IF 8.2
Zhenzhen Su,Weizheng Li,Shang Li,Ruiqi Wang,Dashuang Sheng,Guo-ping Zhao,Hongqian Cao,Lei Zhang
Inflammatory bowel diseases (IBDs) are characterized by dysregulated inflammatory responses, increased reactive oxygen species (ROS), and compromised intestinal barrier function. Current clinical treatments often yield suboptimal responses and significant side effects. Given the great potential of Akkermansia muciniphila (AKK) bacterial membrane components in IBD treatment and the possible pathogenicity of live bacteria, to essentially address these challenges, we develop a natural membrane-based single-cell coating, incorporating a self-assembled AKK bacterial membrane (AKM) and astaxanthin (AST), forming a protective biological barrier on probiotics. Utilizing Escherichia coli Nissle 1917 (EcN) for the oral delivery system, we engineer AKM-AST@EcN nanocoated probiotics, demonstrating exceptional gastrointestinal (GI) tract tolerance and robust bioactivity. Critically, our findings highlight the potential of AKM-AST@EcN as a promising therapeutic approach for IBD treatment while also presenting a distinctive strategy for probiotic oral delivery systems.
研究领域:
微生物学
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医学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Shixiong Zhang,Xinjing Mao,Liping Chang,Mengnan Li,Cong Wei,Hongrong Li,Xiaogang Shen,Kunxu Niu,Runtao Zhang,Yuning Jiang,Xuan Lu,Yahui Song,Liangxing Zhou,Lini Gao,Zhiqin Zhao,Liying Niu,Qian Yang,Yunlong Hou,Yiling Wu
Ethnopharmacological relevance Bazi Bushen Capsule (BZBS), a traditional Chinese medicine formulation composed of multiple bioactive herbal components, has been validated in multicenter randomized double-blind controlled trials for its potent anti-aging properties. Previous studies from our group have demonstrated that BZBS effectively restores gut microbiota homeostasis and attenuates the impairment of intestinal barrier function, thereby ameliorating age-related cognitive decline. However, the specific molecular mechanisms by which BZBS modulates key microbial-metabolite networks to delay brain aging remain poorly understood and warrant further investigation. Aim of the study This study aims to elucidate the key microbiota-metabolite networks through which BZBS improves cognitive function and delays brain aging in senescence-accelerated mouse-prone 8 (SAMP8) mice. Materials and methods Eight-week-old male SAMP8 mice were used as experimental models, randomly divided into Model, BZ-low (0.5 g/kg/d BZBS), BZ-high (1 g/kg/d BZBS), and RAPA (2 mg/kg/d rapamycin) groups. Senescence-accelerated mouse resistant 1 (SAMR1) mice served as the control group. Cognitive function was assessed using the Barnes Maze test and the three-chamber social test. The structural damage and pathological changes in the brain tissue were evaluated through transcranial Doppler, micro-computed tomography, Nissl staining, and Western blot analysis. Next, the intestinal barrier function was detected by hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and immunofluorescence (IF) staining. Characteristic bacteria were identified by 16S rRNA sequencing, and metabolomic profiling was performed using non-targeted metabolomics. Akkermansia muciniphila (Akk) was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate its contribution to intestinal barrier function. Results The study revealed that BZBS therapy not only enhances cognitive capabilities but also restores the intestinal barrier function. Akk was identified as a key regulatory agent mediating the therapeutic effects of BZBS. BZBS administration significantly increased the abundance of Akk and modulated its metabolite profile, particularly components associated with spermidine, thereby reinforcing the intestinal barrier and mitigating age-related cognitive decline. Furthermore, this study demonstrated that Akk, administered via fecal microbiota transplantation, alleviated dextran sulfate sodium (DSS)-induced colitis.. Conclusion The results showed that BZBS capsule, a traditional Chinese medicine, may delay brain aging in SAMP8 mice by modulating Akk and its spermidine production.
研究领域:
民族药理学
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微生物组学
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代谢组学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Microorganisms
·
2021
·Vol. 9
·期 7
·1511
·
IF 4.128
Jia Yin,Yujie Song,Yaozhong Hu,Yuanyifei Wang,Bowei Zhang,Jin Wang,Xuemeng Ji,Shuo Wang
Akkermansia muciniphila, a potential probiotic, has been proven to lessen the effects of several diseases. As established, the relative abundance ofAkkermansiais positively correlated with tryptophan metabolism. However, the reciprocal interaction between tryptophan andAkkemansiais still unclear. Herein, for the first time, the possible effects of tryptophan and its derived metabolites onA. muciniphilawere preliminarily investigated, including growth, physiological function, and metabolism. Obtained results suggested that 0.4 g/L of tryptophan treatment could significantly promote the growth ofA. muciniphila. Notably, when grown in BHI with 0.8 g/L of tryptophan, the hydrophobicity and adhesion ofA. muciniphilawere significantly improved, potentially due to the increase in the rate of cell division. Furthermore,A. muciniphilametabolized tryptophan to indole, indole-3-acetic acid, indole-3-carboxaldehyde, and indole-3-lactic acid. Indoles produced by gut microbiota could significantly promote the growth ofA. muciniphila. These results could provide a valuable reference for future research on the relationship between tryptophan metabolism andA. muciniphila.Keywords:Akkermansia;tryptophan metabolites;indole;indole derivates
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
PubMed
高影响因子
Journal of Translational Medicine
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2025
·Vol. 23
·期 1
·1-19
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IF 7.5
Zhao Zhiqi,Deng Yixuan,Li Li,Zhu Liying,Wang Xin,Sun Haibiao,Li Xiaoqiong,Han Xiaoqiang,Li Jinjun
Background Phytohormones have garnered considerable interest as potential modulators of the gut-bone axis. Denosumab (Deno), a widely utilized therapeutic agent for postmenopausal osteoporosis, has not been previously investigated for its effects on gut health. The objective of this study was to assess the efficacy of isoflavones (SI), naringin (Nar), and Deno in the management of postmenopausal osteoporosis by targeting the gut-bone axis.Methods The postmenopausal osteoporosis model in mice was established via bilateral oophorectomy. Subsequently, mice in the Deno group received subcutaneous injections of Deno at a dosage of 10 mg/kg, administered twice weekly. In contrast, mice in the SI and Nar groups were subjected to oral gavage with 200 mg/kg/day of SI and Nar, respectively. The treatment period for all groups lasted for 8 weeks. Upon the conclusion of the experiment, a thorough evaluation of the effects of SI, Nar, and Deno on bone and gut health in mice was conducted through immunological, pathological, imaging, and multi-omics methodologies.Results Deno, SI, and Nar significantly alleviated the physical symptoms in postmenopausal mice. However, only SI and Nar significantly modulated the gut microbiota. Akkermansia was significantly enriched after the gavage of SI and Nar. Akkermansia has the capacity to not only augment bone mass and alleviate strength deterioration via extracellular vesicles, but it also influences bone metabolism by diminishing inflammation and modulating lipid metabolism. Notably, no significant changes in the gut microbiota were observed in the Deno group, which may be attributed to the differences in the method of administration, as Deno was administered via subcutaneous injection rather than gavage.Conclusion SI and Nar may influence the gut–bone axis through Akkermansia and have the potential of alternative treatment options for postmenopausal osteoporosis. Although the gut microbiota is not significantly affected by the subcutaneous administration of Deno, the long-term management of postmenopausal osteoporosis and the exploration of various management models warrant additional scrutiny. Furthermore, this study has yet to establish a dose–response relationship, indicating that further research is essential to clarify the regulatory effects of varying doses of SI and Nar on postmenopausal osteoporosis especially the modulation of gut microbiota.Graphical
研究领域:
医学
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微生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
PHYSIOLOGY & BEHAVIOR
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2022
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IF 3.742
Yan Sun,Haiyan Zhu,Rongrong Cheng,Zhengquan Tang,Min Zhang
Akkermansia muciniphila is present in the mucus layer of its host gut, and its outer membrane protein Amuc_1100 has a significant ameliorative effect on metabolic disorders and emotional memory aspects of enteritis, obesity, depression, and anxiety in the host. Antibiotics affect gut microbial composition, leading to imbalance and behavioral changes in the gut-brain axis, while probiotics have a protective effect against behavioral changes caused by gut flora disorders. In the present study, a depressed mouse model using a broad-spectrum cocktail mixture resulted in increased anxiety and depression-like behavior, decreased serum and hippocampal levels of 5-hydroxytryptamine (5-HT), and increased serum corticosterone (cort) levels. After application of A. muciniphila and Amuc_1100, anxiety and depression-like behavior in antibiotic-treated mice were significantly alleviated. In addition, the brain derived neurotrophic factor / Tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway was altered, glial fibrillary acidic protein (GFAP) expression increased, and c-Fos protein expression decreased in the hippocampus of antibiotic-treated mice. After treatment with A. muciniphila and Amuc_1100, BDNF and TrkB levels were restored in the hippocampus and cortex. These results suggest that A. muciniphila and Amuc_1100 may alleviate antibiotic-induced anxiety and depression by affecting the BDNF/TrkB signaling pathway.
研究领域:
神经科学
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微生物学
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药理学
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行为科学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2021
·Vol. 12
·期 20
·10184-10195
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IF 5.396
Zhenyang Gu,Wenlong Pei,Yonghua Shen,Lijuan Wang,Jun Zhu,Yi Zhang,Shengxian Fan,Qian Wu,Lei Li,Zhan Zhang
Dietary interventions, including dietary ingredients, nutrients and probiotics, exert anti-inflammatory effects in ulcerative colitis (UC). Our previous study showed that Akkermansia muciniphila (Akk), a promising probiotic, could protect against colitis via the regulation of the immune response. However, whether it can restore aberrant tryptophan (Trp) metabolism during colitis remains unclear. In this study, untargeted serum metabolomics of patients with UC and colitis mice showed that Trp metabolism was activated, which was confirmed by quantification of Trp metabolites from a validation cohort and animal study. Integrative analysis of faecal metagenomes and serum metabolomes revealed significant associations between Akk and three Trp metabolites. Live Akk, pasteurised Akk and Amuc_1100 failed to restore the reduction in Trp metabolites involved in the serotonin pathway in colitis mice. However, live Akk, pasteurised Akk and Amuc_1100 increased kynurenine (Kyn) but decreased 2-picolinic acid (PIC) levels and the PIC/Kyn ratio without regulating any of the genes involved in Trp metabolism, suggesting that they could suppress the Kyn pathway (KP) independent of colon tissue. In addition, they could significantly restore the enrichment of Trp metabolism mediated by faecal microbiota. Specifically, live Akk, pasteurised Akk and Amuc_1100 could significantly offset the reduction in indoleacetic acid (IAA) levels. Pasteurised Akk significantly elevated the serum levels of indole acrylic acid (IA). In addition, live Akk, pasteurised Akk and Amuc_1100 could upregulate aryl hydrocarbon receptor (AhR) targeted genes, including CYP1A1, IL-10 and IL-22, suggesting that Akk could activate AhR signaling by regulating Trp metabolism, thereby attenuating colonic inflammation.
研究领域:
微生物学
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免疫学
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胃肠病学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Journal of Clinical and Translational Hepatology
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2023
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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
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肝病学
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营养学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
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2020
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IF 5.893
Linxin Teng,Kaiyuan Wang,Weiping Chen,Yun-shan Wang,Lei Bi
Traditional Chinese medicine (TCM) plays a vital part in cancer treatment due to its unique superiority. Huoxue Yiqi Recipe-2 (HYR-2) was supposed to have therapeutic effect on lung cancer, which came from Ze Qi Decoction in one of the four great classics of TCM called "Synopsis of Prescriptions of the Golden Chamber". Network pharmacology demonstrated that the targets of active components from HYR-2 were significantly enriched in the signaling pathways, which were closely associated with non-small cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1). Then, data about NSCLC was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET was analyzed by bioinformatics, and 214 biomarkers for NSCLC were obtained, containing 14 targets of active components from HYR-2 (which were significantly enriched in the PD-L1 related signaling pathway). In vivo and in vitro experiments showed that HYR and HYR-2 could inhibit the growth of lung cancer and down-regulate the expression of PD-L1, which might be related to the blocking effect of HYR-2 on the PI3K/Akt signaling pathway. Furthermore, HYR-2 promoted the transformation of M2 macrophages into M1 macrophages as well. It is deserved to be mentioned that the level of Akkermansia muciniphila was also significantly elevated by HYR-2, which was believed to enhance the therapeutic effect of PD-L1 antibodies. To sum up, HYR-2 might play an anti-lung cancer effect by down-regulating PD-L1 together with up-regulating Akkermansia muciniphila.
研究领域:
药理学
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肿瘤学
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微生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Microorganisms
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2024
·Vol. 12
·期 5
·881
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IF 4.1
Xiangyu Meng,Chen Xv,Jiaping Lv,Shuwen Zhang,Changlu Ma,Xiaoyang Pang
The study aims to analyze the composition of the gut microbiota in Chinese individuals using metagenomic sequencing technology, with a particular focus on the abundance ofAkkermansia muciniphila(Akk). To improve the efficiency of Akk isolation and identification accuracy, modifications were made to the enrichment culture medium and 16S rRNA universal primers. Additionally, potential growth-promoting factors that stimulate Akk growth were explored through in vitro screening. The research results revealed that the abundance of Akk in Chinese fecal samples ranged from 0.004% to 0.4%. During optimization, a type of animal protein peptide significantly enhanced the enrichment efficiency of Akk, resulting in the isolation of three Akk strains from 14 fecal samples. Furthermore, 17 different growth-promoting factors were compared, and four factors, including galactose, sialic acid, lactose, and chitosan, were identified as significantly promoting Akk growth. Through orthogonal experiments, the optimal ratio of these four growth-promoting factors was determined to be 1:1:2:1. After adding 1.25% of this growth-promoting factor combination to the standard culture medium, Akk was cultivated at 37° for 36 h, achieving an OD600nmvalue of 1.169, thus realizing efficient proliferation and optimized cultivation of Akk. This study provides important clues for a deeper understanding of the gut microbiota composition in Chinese individuals, while also offering effective methods for the isolation and cultivation of Akk, laying the groundwork for its functional and application research in the human body.
研究领域:
微生物学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2024
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IF 5.1
Lan Sang,Shuyu Yang,Ying Zhu,Zhigang Zhu,Binrui Yang,Ziguang Li,Xin Mao,Siling Chen,Chengsi Li,Jun Du,Xiao Zheng,Hua He,Jianheng Zheng,Yin Huang
B vitamins and probiotics are commonly used dietary supplements with well-documented health benefits. However, their potential interactions remain poorly understood. This study aims to explore the effects and underlying mechanisms of the combined use of B vitamins and probiotics by liquid chromatography-triple quadrupole mass spectrometry analysis, pharmacokinetic modeling, and 16S rRNA gene sequencing. By intragastric administration of seven B vitamins and three Lactobacillus strains to healthy rats (n = 8 per group), we found that probiotics significantly promoted the absorption (by approximately 14.5% to 71.2%) of vitamins B1, B3, B5, and B12. By conducting in vitro experiments (n = 3 per group) and a pseudo-germ-free rat model-based pharmacokinetic study (n = 6 per group), we confirmed that probiotics primarily enhanced the B vitamin absorption through gut microbiota-mediated mechanisms, rather than by directly producing B vitamins. Furthermore, we evaluated the effects of B vitamins and probiotics on the colon and gut microbiota by treating the pseudo-germ-free rats with blank solution, B vitamins, probiotics, and B vitamins + probiotics (n = 5 per group), respectively. Histopathological examination showed that the combination of B vitamins and probiotics synergistically alleviated the rat colon damage. High-throughput genetic sequencing also revealed the synergistic effect of B vitamins and probiotics in modulating the gut microbiota, particularly increasing the abundance of Verrucomicrobia and Akkermansia. In summary, the combined administration of B vitamins and probiotics may have a higher efficacy than using them alone.
研究领域:
营养学
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微生物学
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药理学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2020
·Vol. 21
·期 9
·3385
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IF 4.556
Xin Meng,Jinrui Zhang,Hao Wu,Dahai Yu,Xuexun Fang
Mucin2 (Muc2) is the main component of the intestinal mucosal layer and is highly expressed in mucous colorectal cancer. Previous studies conducted by our lab found that the recombinant protein Amuc_1434 (expressed inEscherichia coliprokaryote cell system, hereinafter termed Amuc_1434*), derived fromAkkermansia muciniphila, can degrade Muc2. Thus, the main objective of this study was to explore the effects of Amuc_1434* on LS174T in colorectal cancer cells expressing Muc2. Results from this study demonstrated that Amuc_1434* inhibited the proliferation of LS174T cells, which was related to its ability to degrade Muc2. Amuc_1434* also blocked the G0/G1 phase of the cell cycle of LS174T cells and upregulated the expression of tumor protein 53 (p53), which is a cell cycle-related protein. In addition, Amuc_1434* promoted apoptosis of LS174T cells and increased mitochondrial ROS levels in LS174T cells. The mitochondrial membrane potential of LS174T cells was also downregulated by Amuc_1434*. Amuc_1434* can activate the death receptor pathway and mitochondrial pathway of apoptosis by upregulating tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). In conclusion, our study was the first to demonstrate that the protein Amuc_1434* derived fromAkkermansia muciniphilasuppresses LS174T cell viability via TRAIL-mediated apoptosis pathway.Keywords:Amuc_1434*;colorectal cancer cells;proliferation;apoptosis;TRAIL
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2025
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IF 9.6
Nianhua Zhang,Xu Zhang,Jiulong Li,Baoyi Li,Shuai Wang,Xiao Liu,Huan Meng,Motao Zhu
While convenient for patient compliance, the efficacy of oral treatments for inflammatory bowel disease (IBD) is often compromised by the dynamic and harsh chemical environment of the gastrointestinal tract, presenting challenges for effective therapeutic management. The pathological complexity of IBD frequently involves multiple factors such as oxidative stress, immune dysregulation, gut microbiome abnormality, and inadequate drug bioavailability, among others. To address these challenges, this project develops an oral nanomedicine platform based on mesoporous silica nanoparticles with a cerium oxide core, further coated with an outer membrane (OM) derived from Akkermansia muciniphila ( Akk ), a beneficial bacteria naturally present in the human gut. This novel nanocomplex, termed “OM-CeMeso,” is evaluated for its enhanced stability, reactive oxygen species (ROS) scavenging capacity, and ability to restore microbiota homeostasis. This project demonstrates that the silica-based nanomaterials’ acid-resistant yet base-degradable properties significantly improved stability in a murine IBD model. The incorporation of cerium oxide nanoparticles (CeO 2 NPs) added further benefits by enhancing ROS scavenging. Notably, the Akk- derived OM coat also increases the diversity and abundance of beneficial gut microbiota. These complementary and integrated functions lead to significant symptom alleviation in murine IBD models while avoiding any unwanted toxicity.
研究领域:
药学
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纳米技术
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胃肠病学
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微生物学
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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）