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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DOI
PubMed
高影响因子
Journal of Translational Medicine
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2025
·Vol. 23
·期 1
·1-19
·
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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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
Microorganisms
·
2024
·Vol. 12
·期 5
·881
·
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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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
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
ACS Nano
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2024
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IF 15.8
Yujie Zhang,Ya Wang,Xiaojiang Zhang,Pengqian Wang,Feiyu Shi,Zhe Zhang,Ruochen Wang,Daocheng Wu,Junjun She
To realize effective and long-term synergistic therapy of ulcerative colitis (UC) with probiotics, we developed gastrointestinal self-adaptive and nutrient self-sufficient Akkermansia muciniphila (AKK)–gelatin porous microgels (AKK@GPMGs). In AKK@GPMGs, AKK was covered with sequential layers of proanthocyanidins (PAs), mucin (MUC), and phosphatidylcholine (PC) to obtain AKK@PAs-MUC-PC (AKK@PMP), and then encapsulated within the methacrylate-modified gelatin porous microgels. AKK@GPMGs provide sufficient mucus as a nutrition source for AKK and boost resistance to stomach acid by 30.49-fold, and colonization in the intestines is enhanced by 83.46 times. The microgels can be dissociated by matrix metalloproteinase at the inflammatory sites of the intestine, and release AKK@PMP, which acts as “band-aid” that adheres to the inflamed colon for a long time and offers improved synergistic therapy for UC. Compared to uncoated AKK, AKK@GPMGs increase reactive oxygen species scavenging capacity by 26.47 times, improve the intestinal mucus layer thickness by 5.63 times, increase the goblet cells abundance by 3.93 times, reduce intestinal permeability by 5.60 times and significantly enhance beneficial gut microbiota while repressing harmful microbiota. These results indicate that AKK@GPMGs can restore mucus layer and tight junction integrity, reduce inflammation and oxidative stress, and regulate gut microbiota homeostasis to effectively treat intestinal inflammation.
研究领域:
药学
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生物医学工程
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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
Acta Crystallographica Section F-Structural Biology Communications
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2020
·Vol. 76
·期 4
·168-174
·
IF 0.968
Mou L.,Peng X.,Chen Y.,Xiao Q.,Liao H.,Liu M.,Guo L.,Liu Y.,Zhang X.,Deng D.
Many human diseases, such as obesity and diabetes, show annual increases in prevalence and often involve intestinal microbes. One such probiotic bacterium, Akkermansia muciniphila, which was discovered a decade ago, has been reported to influence glucose homeostasis and to contribute to gut health. Amuc_1100, a functionally uncharacterized protein of A. muciniphila, was found to be a key active component in reducing the body weight of mice. Here, the crystal structure of Amuc_1100 (residues 31–317), referred to as Amuc_1100*, is reported at 2.1 Å resolution. Amuc_1100* has a similar fold to three proteins related to pilus formation, PilO, PilN and EpsL, indicating a similar function. Biochemical investigations further confirmed a monomeric state for the soluble region of Amuc_1100, which differs from the dimeric states of PilO, PilN and EpsL. This study provides a structural basis for the elucidation of the molecular mechanism of Amuc_1100.
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DOI
高影响因子
CELL
·
2024
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IF 45.5
Qixing Nie,Xi Luo,Kai Wang,Yong Ding,Shumi Jia,Qixiang Zhao,Meng Li,Jinxin Zhang,Yingying Zhuo,Jun Lin,Chenghao Guo,Zhiwei Zhang,Huiying Liu,Guangyi Zeng,Jie You,Lulu Sun,Hua Lu,Ming Ma,Yanxing Jia,Ming-Hua Zheng,Yanli Pang,Jie Qiao,Changtao Jiang
The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo . By activity-based protein purification and identification, we identified an enzyme annotated as β-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila . Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.
研究领域:
医学
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微生物学
✓ 已验证
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2026
·Vol. 32
·期 5
·e70933
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IF 6.6
Xin Nie,Sheng-Yang Zhou,Le Yao,Lu-Lu Tan,Xiao-Yu Ma,Yi-Meng Xia,Chun Cui,Wei-Jiang Zhao,Chen-Meng Qiao,Yan-Qin Shen,Chao-Sheng Li
Aims Sleep disturbances are a potential risk factor for stroke. Our clinical cohort shows that insomnia is associated with a higher 90-day stroke recurrence rate, prompting an investigation into the underlying mechanisms, particularly the role of the gut microbiota. Methods We utilized a rat MCAO model of sleep deprivation (SD) combined with antibiotic (ABX)-induced gut dysbiosis. Neurological deficits were assessed through behavioral tests, and cerebral infarct volume was measured using TTC staining. Structural changes in brain and intestinal tissues were observed by H&E staining, while the expression of blood–brain barrier (BBB)-related proteins was detected by immunofluorescence and Western blot. Gut microbial composition was analyzed by 16S rRNA sequencing, and metabolomic analysis was performed using an untargeted LC–MS approach. Results In rats with an intact microbiota, SD had a limited effect on MCAO-induced ischemic injury. Strikingly, in ABX-induced dysbiosis, SD-exposed rats subjected to MCAO displayed more severe motor deficits, larger infarct volumes, heightened inflammation, and decreased expression of key intestinal and BBB proteins. Microbiota analysis identified Akkermansia as a potential key mediator, whose abundance was significantly decreased in the ABX + SD + MCAO group and negatively correlated with infarct size. Subsequent metabolomics profiling revealed a distinct dysregulation of Akkermansia -associated metabolites (including PG(14:0/15:0), 3-Methylbutylamine, N-Acetylcytidine, and N-Methylisoleucine). Conclusion In conclusion, our study proposes a mechanism whereby SD worsens stroke outcomes by depleting Akkermansia and disrupting metabolic homeostasis.
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DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 21
·3790
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IF 5.1
Teng Zuo,Ziqian Yin,Zhiguo Li,Zhihao Ren,Yaqiang Chen,Dahai Yu,Xuexun Fang
Akkermansia muciniphila(AKK) is a mucin-degrading gut symbiont with emerging probiotic potential. Among its carbohydrate-active enzymes, Amuc_0517, a glycoside hydrolase family 36 (GH36) protein, has been identified as a highly specific α-galactosidase. In this study, the Amuc_0517 gene was cloned into pET-28a(+), expressed inEscherichia coliBL21, and purified via Ni2+-NTA affinity chromatography. Bioinformatic analysis indicated the presence of a signal peptide and α-galactosidase domain. Enzyme assays confirmed its ability to cleave α-1,6-glycosidic bonds in pNPGal, with no detectable activity toward pNPGlu, and molecular dynamics simulations revealed stronger binding affinity and lower free energy with pNPGal, supporting its substrate specificity. Given that α-galactosidases are widely applied in the dairy industry to hydrolyze galactose-containing oligosaccharides in milk and whey, the biochemical features of Amuc_0517 suggest its potential as a novel biocatalyst for functional dairy processing and probiotic-enriched dairy product development.
研究领域:
微生物学
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酶学
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分子生物学
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生物技术
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食品科学
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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）