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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2025
·
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.
研究领域:
食品科学
·
营养学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Translation
·
2026
·
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
✓ 已验证
DOI
PubMed
高影响因子
PHYSIOLOGY & BEHAVIOR
·
2022
·
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2020
·Vol. 21
·期 9
·3385
·
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2026
·
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.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Kangle Li,Hongjie Cui,Si Wang,Qianfu Gan,Qinghua Liu,Shuangbo Huang
Alterations in gut microbiota and its metabolites are associated with placental and fetal development. Although proline has been shown to enhance placental function and improve pregnancy outcomes, its interaction with the gut microbiota remains poorly understood. In this study, a gestational low-protein diet (LPD) leads to decreased fetal birth weight and impaired placental vascular development, as well as increased embryonic resorption rates; these effects are mitigated by dietary proline supplementation. Mechanistically, proline enhances the abundance of Akkermansia and the production of butyrate in the gut, thereby promoting placental angiogenesis by activating the placental Wnt/insulin-like growth factor 1 (Igf1) signaling pathway, ultimately alleviating fetal developmental impairment caused by LPD. Moreover, in an in vitro porcine vascular endothelial cell model under amino acid-restricted conditions, butyrate enhances angiogenesis by activating the Wnt/Igf1 signaling pathway. These findings reveal that targeting the dietary proline supply and gut microbiota may open new avenues for the prevention of intrauterine growth restriction.
✓ 已验证
产品关联
DOI
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Environmental Sciences
·
2025
·
IF 6.3
Gang Wei,Wangrui Liu,Fengjie Shen,Rongrong Xie,Fengwei Wang,Huaqi Guo,Lin Liu
The global rise in intestinal dysfunction has been linked to modifiable risk factors including high-fat diet (HFD)-induced obesity / diabetes, microplastics (MPs) and aging, yet their combined effects remain unclear. This study examined the combined effects of chronic low dose polystyrene MPs (∼25 μg/(kg·day)) with HFD or aging on intestinal barrier function in C57BL/6J mice over 14 weeks. Juvenile mice receiving either normal chow (NCD) or HFD, along with aged NCD-fed mice, were subjected to MPs exposure. Results demonstrated that MPs exposure or HFD feeding (and aging) significantly exacerbated the pathological changes developed in colon tissues of mice relative to those of control mice, including gut permeability, oxidative stress, pro-inflammatory response and apoptosis. Moreover, combination of MPs exposure with HFD feeding (and aging) further potentiated the harmful effects on colon dysfunctions, clearly showing a synergistic deterioration effect (‘double hit’). More importantly, we found that the recovery of colon damages resulting from MPs exposure and HFD feeding was disrupted after their withdrawal, leading to the worse effects on gut microbiota dysbiosis and intestinal function. Furthermore, oral administration of Akkermansia muciniphila prevented intestinal barrier dysfunction and decreased intestinal permeability from MPs exposure and HFD feeding co-exposure. Our findings in this study emphasized the important role of avoiding MPs exposure in the prevention and treatment of intestinal-related dysfunctions, and provided potential therapeutic approaches. The oral administration of gut microbiota, such as Akkermansia muciniphila , contributed to restoration of intestinal barrier function, uncovering a new landscape for treating intestinal disabilities caused by MPs exposure.
研究领域:
环境科学
·
医学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Environmental Sciences
·
2025
·
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Zhouya Bai,Yunhui Zhang,Xiaojun Huang,Denglin Luo,Shaobin Gu,Kangyi Zhang,Shaoping Nie
The gut microbiota is vital in regulating glycolipid metabolism through bile acid pathways, while pectin maintains gut flora balance. Polysaccharides from red kidney beans (RKPs), particularly pectic types, lower blood sugar and lipids, although the mechanism is unclear. Our findings showed that RKP intervention significantly affects primary bile acid synthesis, especially conjugated bile acids, notably taurocholic acid (TCA). Correspondingly, FXR and TGR5 were identified as key receptors in glucolipid metabolism. Further, Akkermansia was proven to be a vital strain and to effectively improve glycolipid metabolism associated with regulating the activity of bile salt hydrolases (BSHs) and bile acid composition, especially for TCA in diabetic mice. Our results provide an antidiabetic mechanism of RKP and suggest that enriched Akkermansia via regulating the vitality of BSH is altered in response to the composition of bile acid, especially for TCA, thereby alleviating glycolipid metabolism through the TCA-FXR/TGR5 axis.
研究领域:
微生物组学
·
代谢生物学
·
内分泌学
·
营养科学
·
分子药理学
·
胆汁酸代谢
·
肠道菌群与宿主互作
✓ 已验证
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）