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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Chinese Journal of Natural Medicines
·
2026
·Vol. 24
·期 1
·59-72
·
IF 4.9
Yang Lin,Zhengmeng Jiang,Zhilu Yu,Tianqing Huang,Wanyu Gui,Ziyuan Wang,Fei Li,Pingting Xiao,Changyin Li,Ehu Liu
Diabetes mellitus (DM) is a chronic disease influenced by gut microbiome disturbances. Honokiol (HON), a low oral bioavailability compound from Magnolia officinalis bark, has demonstrated potential as a treatment for DM. This research investigates the effects of HON on gut microbiota and host metabolism to elucidate its mechanism of action in DM. After 8 weeks of intervention through fecal microbiota transplantation (FMT) or antibiotic treatment, HON improved glucose tolerance and lipid metabolism in a gut microbiota-dependent manner. Specifically, HON administration significantly increased Akkermansia muciniphila (AKK) abundance and modulated tryptophan (TRP) metabolism, as evidenced by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and untargeted/targeted metabolomics analysis. Notably, research revealed that AKK metabolized TRP into tryptamine (TA) and other metabolites in vitro . Both AKK and TA activated the aryl hydrocarbon receptor (AHR) pathway, increasing circulating glucagon-like peptide-1 (GLP-1) levels and ameliorating diabetes-related symptoms in DM mice. These findings indicate that HON’s hypoglycemic effect primarily stems from AHR-GLP-1 pathway activation through targeted modulation of AKK and microbial TRP metabolite TA, potentially enhancing HON’s clinical applications.
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Food & Function
·
2021
·Vol. 12
·期 20
·10184-10195
·
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.
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ACS Applied Materials & Interfaces
·
2025
·
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.
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Foods
·
2025
·Vol. 14
·期 21
·3790
·
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.
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Biochemistry and Biophysics Reports
·
2026
·
IF 2.2
Miao Guan,Lei Li,Yang Zheng,Shaoxing Dai,Runling Wei,Zhenglong Sun
Gut microbes play an important role in the regulation of host health. Multiple studies have shown that Akkermansia muciniphila , as a promising beneficial gut bacterium, is robustly associated with positive effects on host metabolism, immunological regulation, and its presence inversely correlates with body weight. But the precise function played by this bacterium underlying lipid degradation is still unknown. Here we identify a metallophosphoesterase from A. muciniphila. The metallophosphoesterase is composed of a binuclear metal center connected with tyrosine residues and a highly conserved calcineurin-like_PHP_ApaH domain. The enzyme activity has reached its peak in the conditions of pH 8.0, temperature of 37 °C. The enzyme is active for esters with short fatty-acid chains, and has high catalytic activity for hydrolysis of phospholipid sodium salts. In addition, five of predicted active sites of the metallophosphoesterase affecting its enzymatic activity are individually analyzed. Point mutation of H47 reduces the catalytic activity of the metallophosphoesterase for its most preferred substrate, while mutation of H181 has the opposite effect of increasing the enzymatic activity. Overall, we report the first characterization of AMUC-1901, a novel metallophosphoesterase from A. muciniphila with lipid degradation capabilities, which has potential for further exploration in developing novel food or pharma supplements for obesity therapies.
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Frontiers in Cellular and Infection Microbiology
·
2026
·
IF 5.5
Yumeng Chen,Zhenghai He,Xiaowen Shi,Jun Zhang,Lejiao Mao,Zhaoxia Lu,Zhen Zou,Chengzhi Chen,Xia Qin,Yishi Li
Introduction The gut-lung axis plays a critical role in the pathogenesis of acute lung injury (ALI). While intestinal microbiota, particularly Akkermansia muciniphila (AKK), has been linked to the regulation of ALI in adult murine model, its impact on juvenile hosts, who exhibit heightened susceptibility to lipopolysaccharide (LPS)-induced ALI, remains poorly understood. Moreover, despite microencapsulation enhancing the probiotic gastrointestinal survival and colonization of probiotics, the therapeutic potential of microencapsulated AKK (AKK-MC) in juvenile murine ALI has not been explored. Methods In this study, juvenile mice were orally gavaged with live AKK or AKK-MC for 14 days, with LPS-induced ALI established on day 11. Lung tissues were analyzed for morphological changes and inflammatory cytokine analysis. Bronchoalveolar lavage fluid (BALF) was collected for total cell counts and protein concentration. Macrophages and neutrophils infiltration in the lungs was quantified via immunofluorescence staining. Four segments of the intestinal tract (jejunum, ileum, cecum, and colon) were harvested for histological analysis using hematoxylin and eosin (H&E), Alcian blue-periodic acid-Schiff (AB-PAS), and toluidine blue (TBO) staining. These evaluations included measurements of villus height to crypt depth, intestinal injury scoring, and counts of goblet and mast cells. Results AKK-MC treatment resulted in higher fecal abundance of AKK compared to AKK group. AKK treatment attenuated LPS-induced weight loss and mitigated lung damage. This was evidenced by reduced protein concentration and cell counts in BALF, downregulation of Tnf-α and Il-1β expression, improved lung histology, and decreased macrophage infiltration and neutrophil extracellular traps formation. In the intestine, AKK treatment restored mucosal architecture, increased villus height to crypt depth ratios, maintained goblet cell populations, and reduced mast cell infiltration across intestinal segments. Conclusion These results demonstrate that microencapsulation enhances AKK’s efficacy in ameliorating LPS-induced ALI in juvenile mice through gut microbiota modulation. This study provides a crucial foundation for the development of probiotic-based interventions in pediatric ALI.
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Journal of Clinical and Translational Hepatology
·
2023
·
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.
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Journal of Future Foods
·
2025
·
IF 7.2
Mingjing Zheng,Jinhuai Zuo,Huan Ouyang,Tao Hong,Zhipeng Li,Yujia Ou,Yanbing Zhu,Hui Ni,Zedong Jiang
Akkermansia muciniphila plays a key role in maintaining gut barrier integrity, but its interaction with dietary polysaccharides remains unknown. This study investigated the effects of Bangia fusco-purpurea polysaccharide (BFP) on the growth and metabolic activity of A. muciniphila . The results showed that BFP significantly enhanced bacterial growth and short-chain fatty acid production in a dose-dependent manner. Compared with A. muciniphila in a carbon-free medium, integrated proteomic and metabolomic analyses revealed significant changes at the incubation of with 2.00 g/L BFP, including 38 differentially expressed proteins and 157 metabolites. Notably, upregulation of colonization-associated proteins (e.g., MurE, Pyk, GuaB) was observed, along with elevated levels of purine-related metabolites such as guanosine monophosphate and ribose 1-phosphate. Pathway analysis indicated modulation of purine metabolism, cGMP-PKG signaling, and tryptophan metabolism, suggesting that BFP shapes the metabolic adaptation of A. muciniphila in polysaccharide-rich environments. Furthermore, BFP enhanced the expression of MUC-2 and tight junction proteins (ZO-1, Occludin, Claudin), implying the improved intestinal barrier-enhancing effect. These findings demonstrated that BFP can promote A. muciniphila colonization through metabolic reprogramming, supporting its potential application in microbiota-targeted dietary strategies.
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Foods
·
2026
·Vol. 15
·期 9
·1467
·
IF 6
Yuqin Wang,Kexin Yu,Tongyan Shen,Kunqing Huang,Mengdie Li,Yating Wang,Jiaqi Xi,Jintian Chen,Minjie Gao,Zhitao Li
Akkermansia muciniphila, a next-generation probiotic in the human intestinal mucus layer, exhibits significant health-promoting properties. However, traditional static culture systems fail to replicate the dynamic peristaltic environment of the gastrointestinal tract, limiting understanding of its metabolic characteristics. This study employed an improved gastrointestinal bioreactor simulating intestinal peristalsis to investigateA. muciniphilagrowth dynamics and metabolomic profiles under dynamic conditions. Dynamic cultivation significantly enhanced bacterial growth. Biomass reached 1.32 ± 0.03 g/L in bovine heart infusion (BHI) medium and 2.03 ± 0.05 g/L in BHI supplemented with 2.5 g/L porcine mucin. These values represent increases of 45.05% and 123.08% relative to static BHI cultures, respectively. Dynamic conditions markedly elevated short-chain fatty acid production (acetic, propionic, isobutyric, isovaleric acids). Untargeted metabolomics identified 1463 metabolites with 1294 showing significant differential expression. Dynamic cultivation substantially altered amino acid biosynthesis, fatty acid, purine, and pyrimidine metabolism. These findings advance the understanding ofA. muciniphilaphysiology and provide insights into its metabolic characteristics under simulated intestinal conditions.
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PHARMACOLOGICAL RESEARCH
·
2020
·
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.
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Food Bioscience
·
2026
·
IF 6.2
Mingjing Zheng,Jinhuai Zuo,Binhui Zhou,Tao Hong,Yuanfan Yang,Zedong Jiang,Hui Ni,Yujia Ou
The effect of ultra-high pressure (UHP)-modified Bangia fusco-purpurea polysaccharides (UBFP) on the growth and metabolic profile of Akkermansia muciniphila, as well as the lipid-regulatory effects of its fermentation products, were investigated. Compared with native BFP, UBFP treated under moderate UHP conditions (200–400 MPa) was found to more effectively promote the growth and polysaccharide utilization of A. muciniphila . In oleic acid-induced HepG2 cells, significant reductions in triglyceride levels and lipid droplet accumulation were observed after treatment with UBFP fermentation products ( p < 0.05), particularly in the UBFP 400 group, which exhibited 12.5% and 20.07% greater reductions than the BFP group, respectively. Metabolomics and proteomics analyses suggested that UBFP fermentation products may influence lipid homeostasis through alterations in lipid-related metabolites and proteins, including hypoxanthine, inosine, FABP3, PLIN4, ALB, FABP4, and SCD5. These alterations were mainly associated with AMPK/ACC-related signaling and several metabolic pathways, including purine metabolism, fatty acid metabolism, and the p53 signaling pathway. These findings provide a theoretical basis for the development of A. muciniphila -mediated algal polysaccharide functional ingredients targeting lipid metabolism.
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