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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Acta Crystallographica Section F-Structural Biology Communications
·
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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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
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PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2026
·Vol. 32
·期 5
·e70933
·
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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高影响因子
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.
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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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 CHEMISTRY
·
2022
·
IF 9.231
Xiaoxiang Gao,Chenbo Yue,Ruocen Tian,Leilei Yu,Fengwei Tian,Jianxin Zhao,Wei Chen,Qixiao Zhai
We examined the microbial regulatory capacity of four polyphenols with different structure in healthy mice and explore the mechanism according to exogenous metabolites and microbial metabolites. Oral administration of four polyphenols, including caffeic acid (CA), procyanidin (PA), puerarin (Pue), and resveratrol (Res), did not lead to metabolic disorder in healthy mice. Gut microbiota analysis revealed that CA, PA, and Pue administration significantly enhanced the abundance of Akkermansia and Ruminococcaceae UCG-014 while Res supplement mainly promoted the growth of Lactobacillus and Bacteroides . Furthermore, correlation analysis and exogenous metabolite prediction revealed that the effects of polyphenols, including CA, PA, and Pue, on Akkermansia have strong relationship with uridine while the regulation of Res on microbiota might be dependent on the decrease on petroselinic acid. These investigations considerably suggest the importance of exploration of exogenous metabolites and reveal the similarity of effects of polyphenols on microbiota and metabolites.
研究领域:
微生物学
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营养学
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代谢组学
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Food & Function
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2024
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IF 5.1
Pengfei Ren,Biqian Wei,Wanting Qin,Qingjuan Tang,Yuming Wang,Changhu Xue
This study utilized in vitro colonic fermentation to examine the impact of astaxanthin on the microbial catabolism of tryptophan. Astaxanthin significantly altered the gut microbiota and raised the tryptophan catabolism metabolite levels in an in vitro human colonic fermentation system. To eliminate the influence of substrate availability, we conducted in vitro colonic fermentation of the gut microbiota of astaxanthin-domesticated mice. We observed that the capacity of astaxanthin-domesticated gut microbiota to catalyze the conversion of tryptophan to indole and derivatives was considerably augmented. Astaxanthin significantly increased the relative abundance of Akkermansia, Ruminococcus, Bacteroides and Lactobacillus and elevated the levels of indole-3-lactic acid and indole-3-propionic acid. These results demonstrated that astaxanthin regulates tryptophan metabolism by modifying gut microbiota and increasing the levels of indole metabolites, such as indole-3-lactic acid and indole-3-propionic acid. This study provides insights into the physiological activity of astaxanthin and sheds light on the potential for enhancing tryptophan metabolism through dietary manipulation of the gut microbiota.
研究领域:
营养学
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微生物学
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代谢组学
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PubMed
高影响因子
Food Bioscience
·
2025
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IF 5.9
Zhengyu Wang,Quanhong Lv,Liangzhong Liu,Zhe Zhu
Constipation is a gastrointestinal disorder related to intestinal flora imbalance and inflammation. Numerous clinical studies have affirmed the efficacy of psyllium husk powder (PHP) in alleviating constipation; however, the efficacy and specific mechanism of PHP in alleviating constipation still lack comprehensive and in-depth discussions. In this study, we comprehensively investigated the mechanism by which round-bracted psyllium husk powder improves loperamide hydrochloride-induced constipation in mice, focusing on gut microbiota and fecal metabolic profiles while comparing the effects of PHP interventions at varying doses to polyethylene glycol 4000 bulk treatment for a comprehensive evaluation of PHP's efficacy in alleviating constipation. Our findings revealed that PHP significantly reduced defecation time and increased fecal output, weight, water content, intestinal motility, and short-chain fatty acid (SCFA) concentrations while positively influencing intestinal inflammation and promoting repair of the intestinal barrier, and higher doses of PHP demonstrate optimal efficacy. Furthermore, PHP markedly modified the microbial composition in constipated mice by enhancing the abundance of beneficial bacteria, particularly Akkermansia muciniphila . UPLC-QTOF-MS/MS analyses indicated that PHP contributed to elevated levels of Cucurbitacin B, BIX 01294 Trihydrochloride along with peptides like Asp-Gly-Lys-Ile-Leu and Val-Met-Met-Val-Arg among other potentially beneficial metabolites. KEGG pathway analysis revealed that PHP alleviates constipation by modulating metabolic pathways associated with SCFA production, beneficial microbiota colonization, and the reduction of intestinal inflammation, encompassing ABC transporters, biosynthesis of unsaturated fatty acids, and galactose metabolism etc. In conclusion, PHP can effectively relieve constipation by remodeling the structure of the gut microbiota while enhancing its associated metabolic pathways and products.
研究领域:
医学
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微生物学
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代谢组学
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高影响因子
Biochemistry and Biophysics Reports
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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
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2026
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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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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Hongxuan Li,Yubo Zhang,Yaping Zheng,Xuejian Li,Zimu Li,Chaoxin Man,Yu Zhang,Yujun Jiang
The probiotic strain Bacillus amyloliquefaciens JM033 ( B. amyloliquefaciens JM033), isolated from the traditional Chinese fermented food Sufu (also known as Fu-ru or fermented bean curd), is distinguished by its high production of exopolysaccharides (EPS). The EPS (BAP-1) produced by this strain was purified and its structure analyzed. BAP-1 is a novel hybrid fructan with a molecular weight of 17.6 kDa. It is composed of →6)- β -D-Fru f -(2 → and →1,6)- β -D-Fru f -(2→, which form the backbone, with a branched chain of β -D-Fru f -(2 → attached at the 1-position of residue B. In vivo studies on mice indicated that BAP-1 improves immunity in immunosuppressed mice by enhancing humoral immunity ( P < 0.01), monocyte-macrophage phagocytosis ( P < 0.01), and NK cell killing activity ( P < 0.05). Additionally, BAP-1 was found to improve the composition of the intestinal microbiota and stimulate the production of short-chain fatty acids. Notably, BAP-1 exhibited a significant effect on the proliferation of Akkermansia . Therefore, BAP-1 shows promise as a prebiotic and may contribute to the development of new immunomodulatory agents.
研究领域:
微生物学
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免疫学
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营养学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）