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.
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Journal of Advanced Research
·
2026
·
IF 17.1
Yuting Zhang,Ruopeng Yin,Wang Dong,Li Sun,Tao Wang,Jingzu Sun,Huanqin Dai,Yanliang Bi,Liangliang Wang,Hongwei Liu
Introduction Sepsis is a life-threatening syndrome of organ dysfunction driven by a dysregulated immune response. Effective therapeutic strategies to restore immune homeostasis remain limited. Hypoacylated lipooligosaccharides (ALOS) from Akkermansia muciniphila have emerged as potential immunomodulatory postbiotics, yet their therapeutic potential in sepsis and the underlying mechanisms remain unexplored. Objectives This study aims to investigate whether ALOS confers protection in experimental models of sepsis induced by toxic lipopolysaccharides (LPS) or cecal ligation and puncture (CLP), and the mechanism by which ALOS exerts its anti-inflammatory and regulatory effects. Methods In LPS or CLP-induced mouse sepsis models and a porcine sepsis model, ALOS (0.2 mg/kg, i.p.) was administered once every two days before challenge or half an hour post-surgery. Survival rates, physiological and biochemical parameters were assessed. Based on 16S rRNA gene amplicon sequencing and barrier function assessment, the changes of the colonic microbiota and metabolites and anti-inflammatory capacity were analyzed. The anti-inflammatory and immunomodulatory mechanisms of ALOS were investigated through dendritic cell phenotyping, transcriptomic analysis, inhibitor assays, and conditioned medium experiments. Finally, the safety of ALOS was evaluated in C57BL/6J mice following one-week administration (0.2 mg/kg, i.p.). Results ALOS pretreatment significantly suppresses sepsis, reduces the proportion of pro-inflammatory Th17 cells, and increases regulatory T cells (Treg). Mechanistically, ALOS induced semi‑mature dendritic cells with upregulated IDO1 expression, leading to enhanced production of kynurenine (Kyn). Kyn activated the aryl hydrocarbon receptor (AhR) to drive Treg differentiation. The protective effect of ALOS was completely reversed by NLG919, whereas Kyn administration mimicked the therapeutic benefit. ALOS also produced therapeutic protection on sepsis. In a porcine sepsis model, pretreatment of ALOS exerted systemic anti‑inflammatory effects and protected multiple organs. Conclusion This study highlights the protective role of ALOS in sepsis and identifies the IDO1-Kyn-AhR immune axis as the major underlying mechanism.
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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.
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Journal of Orthopaedic Translation
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2026
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IF 9.8
Yimin Pi,Haodong Zhu,Jian Xie,Furui Tang,Zhuoya Wang,Li Liu,Yuchun Zhong,Zhidong He,Tian Liu,Jiacheng Zheng,Yuwen Tang,Jun Luo,Cihua Zheng
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder frequently accompanied by extraintestinal complications such as bone loss, yet effective treatment options remain elusive. In this study, we investigated whether hesperetin mitigates colitis-associated bone loss by modulating the “gut–bone axis.” Using a DSS-induced mouse model of chronic colitis, we found that hesperetin significantly reduced intestinal inflammation, restored mucosal barrier integrity, and suppressed serum inflammatory cytokines. Furthermore, hesperetin effectively alleviated DSS-induced bone microstructure damage, promoted the expression of ALP, Runx2, OCN, and inhibited NFATc1 and CTSK. Fecal microbiota transplantation experiments further confirmed that the intestinal microbiota from hesperetin-treated group attenuated intestinal inflammation and bone loss. 16S rRNA sequencing and metabolomics revealed that hesperetin enriched Akkermansia muciniphila ( A. muciniphila ) and increased the tryptophan metabolite 3-indoleacrylic acid (IDA). Supplementation with A. muciniphila or IDA alone simulated the therapeutic benefits of hesperetin. Furthermore, RNA-seq revealed that hesperetin regulated bone metabolism-related gene expression by ECM-receptor interaction and PI3K-AKT signaling, while inhibiting the NOD-like receptor pathway. In conclusion, hesperetin mitigates intestinal inflammation and bone homeostasis imbalance by reshaping the gut microbiota, enriching A. muciniphila, and promoting IDA production, thus providing new insights into potential therapies for IBD-related bone loss. Download: Download high-res image (369KB) Download: Download full-size image
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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
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Probiotics and Antimicrobial Proteins
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2025
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IF 4.4
Ma Xue-Ke,Shao Xin,Xu Tian,Yan Hong,Teng Hui,Chen Zhe-Xin,Hu Meng-Xin
Astaxanthin (ASX) gains wide interest in food and nutritional sciences due to its great antioxidant and anti-inflammatory properties. However, ASX faces challenges such as poor water solubility, low bioavailability, and sensitivity to environmental factors. In this study, we employ Akkermansia muciniphila ( AKK ) with mucoadhesive property as a carrier for ASX to enhance ASX stability and bioaccessibility. The complex multilayered cell envelope of AKK cell provided space for ASX loading. Immersion loading yielded the highest ASX encapsulation efficiency (10.80 ± 2.29 μg/mg in ASX@ AKK group and 11.47 ± 3.52 μg/mg in ASX@ AKK -Heat group), whereas osmoporation loading and vacuum loading yielded ASX encapsulation efficiencies of 4–6 μg/mg. The encapsulated ASX demonstrated improved thermostability, tolerating pasteurization, and was predominantly amorphous in state, interacting with AKK primarily through hydrophobic interactions and partial hydrogen bonding interactions. The ASX@ AKK system facilitated precise ASX release in the intestine and markedly enhanced bioaccessibility, increasing approximately 25.7-fold in simulated intestinal fluid and 77.6-fold in simulated colonic fluid. Importantly, ASX encapsulation did not impair AKK ’s adhesive affinity to mucus. Therefore, the newly developed integrated dietary supplements have both the functional activity of inactivated AKK as a postbiotic and the antioxidant property of the intestine-targeted released ASX, showing dual-functional activities. These findings highlight a paradigm shift in the functional application of probiotics, showcasing their potential as innovative vehicles for targeted nutrient delivery with improved bioaccessibility and synergistic health effects.
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Food & Function
·
2026
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IF 6.3
Ziyuan Zhou,Xiaxia Pan,Jiali Ni,Zhuoqi Lou,Yangfan Shen,Shiman Jiang,Xiangmin Dong,Fengjiao Wang,Yanfei Chen,Lanjuan Li
Existing evidence indicates that pre-existing metabolic dysfunction-associated steatotic liver disease (MASLD) confers susceptibility to acute liver injury (ALI). Nevertheless, the underlying mechanism prompting ALI risk in such condition is not fully uncovered yet. Gut dysbiosis has been well-documented in MASLD patients which prompts us to hypothesize that gut dysbiosis may serve as a contributing factor and regulating target to ALI susceptibility. A case-control study was performed and verified the increased risk of ALI in MASLD patients. Mice pretreated with MASLD mice/patients-derived fecal microbiota transplantation (FMT), demonstrated worsened ALI after D-GalN/LPS injection. We identified significant gut dysbiosis with decreased microbial α-diversity, beneficial genus lactobacillus, increased potential harmful bacteria Campylobacter and helicobacter. Probiotic Akkermansia muciniphila (A. muciniphila) was reported to improve gut dysbiosis. Thus, we tested the effect of A. muciniphila on ALI mice pretreated with MASLD mice-derived FMT. A. muciniphila significantly ameliorated the worsened ALI and improved gut dysbiosis. Transcriptomic analysis reveled that A. muciniphila restored the impaired liver PPAR-α signaling, alleviating the aggravated NF-κB signaling and downstream inflammation response in liver. Specifically, A. muciniphila restored the decreased abundance of PPAR-α agonist daidzein in colon, thereby restoring PPAR-α activation and inhibiting NF-κB signaling in liver. Daidzein is also capable to ameliorate ALI aggravated by MASLD-associated dysbiosis, accompanied by PPAR-α activation and NF-κB inhibition. Our findings revealed that gut dysbiosis in MASLD increased the risk of ALI. A. muciniphila exhibited preventive potential for MASLD patients to reduce ALI risk. Daidzein/PPAR-α/NF-κB signaling is important to maintain host resistance to hepatoxic challenge.
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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.
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Food Science & Nutrition
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2024
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IF 3.5
Xi Chen,Yong Zhu,Muhammad Mazhar,Likang Qin
Camellia seed oil (CSO), a potential prebiotic agent, can significantly increase the relative abundance of Akkermansia muciniphila ( A. muciniphila ) in mice gut microbiota following oral administration, this study aims to investigate the enhancing effect in vitro. The results showed that after 24-h co-cultivation with 0.5% (v/v) CSO, the growth of A. muciniphila increased from 11.61 ± 0.04 Log 10 CFU/mL to 12.17 ± 0.10 Log 10 CFU/mL ( p < 0.05), accompanied by a reduction in the oxidation–reduction potential (ORP) value of the media from −126.67 ± 1.78 mV to −117.33 ± 0.72 mV ( p < 0.05). Additionally, squalene and (+)-α-tocopherol, bioactive compounds present in CSO, were found to promote A. muciniphila proliferation (squalene OD 600 : 1.086 ± 0.002, tocopherol OD 600 : 1.100 ± 0.003, DMSO control OD 600 : 0.991 ± 0.003, p < 0.0001). Transcriptomic and metabolomic profiling revealed 464, 121, and 194 differentially expressed genes (DEGs) and 212, 160, and 156 differentially expressed metabolites (DEMs) in A. muciniphila co-cultivated with CSO after 4, 16, and 24 h, respectively ( p < 0.05). The upregulated DEGs and DEMs were primarily enriched in pathways associated with energy generation (e.g., gap , icd , sucC , GOZ73_RS04175 , succinate, phosphoenolpyruvate), nucleotide metabolism (e.g., mazG, deoxyguanosine), amino acid metabolism (e.g., argF , metK, L-tyrosine), translation (e.g., rplO , rpmC ), and environmental adaptation (e.g., murA , katE , reduced nicotinamide adenine dinucleotide). These findings suggest that various bioactive compounds present in CSO exhibit prebiotic effects on the in vitro proliferation of A. muciniphila by facilitating nutrient utilization and environmental adaptation. This study provides insights into the extended utilization of CSO.
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Advanced Science
·
2026
·
IF 14.1
Kaiyuan Jiang,Fen Xiong,Yiwen Peng,Lingfei Meng,Xinran Wang,Yingruo Xu,Tian Tang,Hongchang Gao
Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes with limited effective interventions. Using a streptozotocin-induced insulin-deficient, type 1 diabetes-like DCM mouse model, we show that intermittent fasting (IF) improves cardiac function and attenuates myocardial remodeling. Antibiotic-mediated microbiota depletion largely abolished these benefits, whereas fecal microbiota transplantation from IF-treated donors recapitulated cardioprotection, supporting a causal role of the gut microbiota. Metagenomic profiling identified Akkermansia muciniphila ( A. muciniphila ) as a prominent IF-responsive taxon, and A. muciniphila supplementation alleviated cardiac injury without obvious improvement in glycaemia. Integrated serum and heart metabolomics identified 1-methyl-L-histidine as a microbiota-associated metabolite reduced in diabetes but restored by IF and A. muciniphila . In vitro and ex vivo assays further supported an L-anserine-linked microbial route for 1-methyl-L-histidine generation. Importantly, oral 1-methyl-L-histidine supplementation recapitulated key cardioprotective effects, remodeled cardiac lipid homeostasis, and reduced lipid peroxidation and oxidative injury. Together, these findings support a gut microbiota–metabolite–lipid axis associated with IF-related cardioprotection in DCM and highlight microbial metabolites as tractable targets to complement dietary intervention.
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Journal of Environmental Sciences
·
2025
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IF 6.3
Mengxing Cui,Shilin Chen,Zhihan Zhang,Yongjiang Yu,Yingxi Xu,Ludi Liu,Huan Gao,Xiaoyu Chen,Ziqi Liu,Xue Zhang,Wenke Yuan,Shen Chen,Daochuan Li,Liping Chen,Xiumei Xing,Yongmei Xiao,Wen Chen,Yan Liu,Qing Wang
The global incidence of inflammatory bowel disease (IBD) has been escalating. Recent studies have identified co-exposure to polystyrene nanoplastics (PSNP) and triclosan (TCS), two prevalent environmental pollutants, as emerging risk factors for IBD. However, the molecular mechanisms contributing to its deteriorative effect remain elusive. To explore the mechanisms, we conducted an integrative analysis of metagenomic and metabolomic data in a mouse model of colitis induced by dextran sulfate sodium (DSS) following co-exposure to PSNP and TCS. Results demonstrated that co-exposure to PSNP and TCS significantly exacerbated DSS-induced colitis, as evidenced by elevated disease activity indices and pro-inflammatory cytokine levels. Mechanistically, this aggravation correlated with a marked reduction in Akkermansia muciniphila abundance, which was further associated with the disruption of tryptophan metabolism. Specifically, the disruption of this metabolic pathway led to decreased production of two key tryptophan-derived metabolites: indole acetic acid (IAA) and indole acetamide (IAM). In-vitro experiments confirmed that co-exposure to PSNP and TCS inhibited the growth of Akkermansia muciniphila rather than affecting the integrity of intestinal epithelial cells. Additionally, IAA and IAM reduced inflammatory cytokine secretion in THP-1 cells. These findings suggest that the reduction in Akkermansia muciniphila abundance might decrease the production of IAA and IAM by disrupting tryptophan metabolism. This disruption ultimately contributes to the inflammatory response induced by co-exposure to PSNP and TCS. Our study offers a novel insight into microbiota-host interactions and potential therapeutic targets for intestinal disease.
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Microorganisms
·
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.
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