Medicine in Microecology最新文献

In-silico analysis, molecular docking and dynamic simulation of anti-cancer metabolites derived from Bacillus velezensis 韦氏芽孢杆菌抗癌代谢物的硅晶分析、分子对接及动态模拟

Q2 Medicine

Medicine in Microecology

Pub Date : 2026-01-07 DOI: 10.1016/j.medmic.2026.100165

Zabin K. Bagewadi , Deepak A. Yaraguppi , Sikandar I. Mulla , Vishal S. Patil , Muskan M. Naik

The complex nature of cancer poses significant challenges in deciphering its underlying molecular mechanisms. To facilitate advancements in biological research and therapeutic development, computational models have emerged as powerful tools for elucidating cancer biology. In the present study, in-silico approaches were employed to identify metabolites from Bacillus velezensis strain with anticancer potential by targeting protein molecules associated with malignancies. Genome mining revealed biosynthetic potential of the strain, and target prediction was conducted using BindingDB (p ≥ 0.7). Pathway enrichment analysis was performed using STRING and KEGG databases, which showed involvement of compounds in modulation of multiple pathways involved in cancer. Molecular docking simulations showed that fengycin, a secondary metabolite derived from B. velezensis, exhibited strongest binding affinity toward MAPK9, with a docking energy of −17.1 kcal/mol. This interaction was validated through Molecular Dynamics (MD) simulation. The mean RMSD values for the APO and MAPK9 complexes were 0.29 ± 0.03 nm and 0.32 ± 0.03 nm, respectively, confirming structural stability throughout the simulation. The mean radius of gyration (Rg) values were 2.33 ± 0.02 nm for APO and 2.35 ± 0.02 nm for MAPK9, indicating compactness of the protein-ligand complex. RMSF values were recorded as 0.15 ± 0.09 nm for APO and 0.14 ± 0.07 nm for MAPK9, reflecting minimal residue-level fluctuations. Solvent Accessible Surface Area (SASA) remained stable at 177.63 ± 5.8 nm² for APO and 179.67 ± 3.4 nm² for MAPK9, suggesting no significant conformational alterations. Additionally, MAPK9 displayed a van der Waals energy of −493.903 ± 17.608 kJ/mol, electrostatic energy of −118.975 ± 26.098 kJ/mol, polar solvation energy of 480.496 ± 21.551 kJ/mol, and a final binding energy of −189.266 ± 33.873 kJ/mol, indicating a strong and stable interaction with the drug candidate. Overall, metabolites derived from B. velezensis, particularly fengycin, demonstrated potential anticancer attributes and warrant further experimental validation.

癌症的复杂性质在破译其潜在的分子机制方面提出了重大挑战。为了促进生物学研究和治疗发展的进步，计算模型已经成为阐明癌症生物学的有力工具。在本研究中，采用计算机方法通过靶向与恶性肿瘤相关的蛋白质分子，鉴定具有抗癌潜力的velezensis芽孢杆菌菌株的代谢物。基因组挖掘揭示了菌株的生物合成潜力，并利用BindingDB进行靶标预测（p≥0.7）。使用STRING和KEGG数据库进行通路富集分析，发现化合物参与了与癌症相关的多种通路的调节。分子对接模拟结果表明，白霉次级代谢物凤霉素对MAPK9的结合亲和力最强，对接能为- 17.1 kcal/mol。通过分子动力学（MD）模拟验证了这种相互作用。APO和MAPK9复合物的平均RMSD值分别为0.29±0.03 nm和0.32±0.03 nm，证实了整个模拟过程中的结构稳定性。APO的平均旋转半径（Rg）为2.33±0.02 nm， MAPK9的平均旋转半径（Rg）为2.35±0.02 nm，表明该蛋白-配体复合物的紧密性。APO的RMSF值为0.15±0.09 nm， MAPK9的RMSF值为0.14±0.07 nm，反映了最小的残留水平波动。APO的溶剂可及表面积（SASA）稳定在177.63±5.8 nm2， MAPK9的SASA稳定在179.67±3.4 nm2，没有明显的构象变化。此外，MAPK9的范德华能为- 493.903±17.608 kJ/mol，静电能为- 118.975±26.098 kJ/mol，极性溶剂化能为480.496±21.551 kJ/mol，最终结合能为- 189.266±33.873 kJ/mol，表明MAPK9与候选药物具有强而稳定的相互作用。总的来说，来自白螺旋体的代谢物，特别是风霉素，显示出潜在的抗癌特性，值得进一步的实验验证。

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引用次数: 0

Phytomolecule and microbiota-modulation based therapeutic strategies for MDR-Tuberculosis: Mechanistic interplay and translational perspectives 基于植物分子和微生物群调节的耐多药结核病治疗策略：机制相互作用和翻译观点

Q2 Medicine

Medicine in Microecology

Pub Date : 2025-12-23 DOI: 10.1016/j.medmic.2025.100163

Sobhanjan Bhunia , Nilanjan Adhikari , Biplab Kumar Chakra , Suman Ghosh , Sajal Kumar Jha , Ishita Debnath , Mithun Bhowmik , Sonia Mallick , Piyali Basak , Rajarshi Das , Sourav pal , Tamalika Chakraborty

Multidrug-resistant tuberculosis (MDR-TB) continues to represent a critical global health challenge due to resistance against first- and second-line anti-TB drugs. Emerging evidence highlights the pivotal role of the human microbiota in TB pathogenesis, immune regulation, and drug response. This review systematically explores the microbiota–MDR-TB axis, with a focus on phytomolecule-based therapeutic interventions. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, Google Scholar, and Elsevier ScienceDirect following PRISMA guidelines, covering studies from January 2004 to August 2025. Included studies encompassed in vitro, in vivo, and clinical investigations elucidating microbiota alterations during TB infection and therapy, mechanistic insights into microbiota-derived metabolites (short-chain fatty acids, indoles), and their regulation of host immunity through AMPK–mTOR signaling, autophagy, and Treg/Th1 cell balance. Our analysis reveals that TB-associated gut and lung dysbiosis leads to SCFA depletion, epithelial barrier disruption, and systemic inflammation, weakening granuloma integrity and favoring M.tb persistence. Phytomolecules such as curcumin, emodin, resveratrol, and berberine exhibit dual actions by exerting direct antimycobacterial effects while simultaneously restoring the microbiota. These effects help reprogram immune responses through PRR, AHR, and AMPK pathways. Additionally, microbiota-sparing drug formulations, including ridinilazole, cadazolid, and lolamicin, along with probiotics, prebiotics, and synbiotics, demonstrate potential as adjunctive strategies to mitigate dysbiosis and enhance treatment outcomes. This review provides a mechanistic and translational framework for integrating phytomolecules and microbiome-modulating approaches into precision therapy, supporting the development of microbiota-informed host-directed therapies for MDR-TB.

由于对一线和二线抗结核药物的耐药性，耐多药结核病（MDR-TB）继续是一项重大的全球卫生挑战。新出现的证据强调了人类微生物群在结核病发病、免疫调节和药物反应中的关键作用。这篇综述系统地探讨了微生物-耐多药结核病轴，重点是基于植物分子的治疗干预。根据PRISMA指南，在PubMed、Scopus、Web of Science、b谷歌Scholar和Elsevier ScienceDirect中进行了全面的文献检索，涵盖了2004年1月至2025年8月的研究。包括体外、体内和临床研究，阐明结核感染和治疗过程中微生物群的改变，微生物群衍生代谢物（短链脂肪酸、吲哚）的机制，以及它们通过AMPK-mTOR信号、自噬和Treg/Th1细胞平衡对宿主免疫的调节。我们的分析表明，结核病相关的肠道和肺部生态失调导致SCFA耗竭、上皮屏障破坏和全身炎症，削弱肉芽肿的完整性，有利于结核分枝杆菌的持续存在。植物分子如姜黄素、大黄素、白藜芦醇和小檗碱表现出双重作用，在发挥直接抗细菌作用的同时恢复微生物群。这些作用有助于通过PRR、AHR和AMPK途径重新编程免疫反应。此外，保留微生物群的药物制剂，包括利地尼唑、卡达唑和洛拉霉素，以及益生菌、益生元和合成菌，显示出作为缓解生态失调和提高治疗效果的辅助策略的潜力。这篇综述为将植物分子和微生物组调节方法整合到精确治疗中提供了一个机制和翻译框架，支持开发微生物群知情的耐多药结核病宿主定向治疗方法。

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引用次数: 0

Pilot study of Raman-deep learning integration for rapid detection of antibiotic-resistant Escherichia coli: A proof-of-concept analysis 拉曼-深度学习集成快速检测耐药大肠杆菌的试点研究：概念验证分析

Q2 Medicine

Medicine in Microecology

Pub Date : 2025-12-22 DOI: 10.1016/j.medmic.2025.100162

Xinkui Chang , Bo Zhou , Limei Yu , Liying Sun , Haixia Li , Anpei Ye

In recent years, the accelerating emergence of antibiotic-resistant bacterial pathogens has posed profound challenges to the therapeutic management, prophylactic strategies, and epidemiological control of infectious diseases caused by these microorganisms. Consequently, identifying resistant bacteria is essential for therapeutic decisions and epidemiological studies. However, conventional approaches for the detection of antibiotic resistance are frequently constrained by lengthy protocols, substantial costs, and operational intricacies, thereby impeding the rapid and precise identification of resistance phenotypes. Raman optical tweezers have proven useful for classifying different bacterial species and isolates. This study establishes a fast, reliable, and cost-effective method to differentiate between Escherichia coli strains with antibiotic resistance (extended spectrum β-lactam resistant, ESBL) and susceptible strains using Raman optical tweezers and deep learning techniques. High-quality single-cell Raman spectra were collected from antibiotic-resistant and susceptible strains without exposure to antibiotics, revealing a higher nucleic acid/protein ratio in resistant strains. We propose a new network, RamanU-Net, for the accurate classification of these Raman spectra. The model achieved 99.5 % average accuracy in identifying antibiotic-resistant and sensitive strains of Escherichia coli. Our results demonstrate that combining Raman optical tweezers with deep learning models can enable rapid identification of bacterial antibiotic resistance while significantly reducing the associated time, cost, and workload.

近年来，耐药细菌病原体的加速出现对这些微生物引起的传染病的治疗管理、预防策略和流行病学控制提出了深刻的挑战。因此，鉴定耐药细菌对治疗决策和流行病学研究至关重要。然而，检测抗生素耐药性的传统方法经常受到冗长的方案、高昂的成本和操作复杂性的限制，从而阻碍了快速准确地识别耐药性表型。拉曼光镊已被证明对分类不同的细菌种类和分离物是有用的。本研究利用拉曼光镊和深度学习技术，建立了一种快速、可靠、经济的方法来区分具有抗生素耐药性（扩展谱β-内酰胺耐药，ESBL）的大肠杆菌菌株和敏感菌株。对未接触抗生素的耐药菌株和敏感菌株采集了高质量的单细胞拉曼光谱，结果显示耐药菌株的核酸/蛋白比较高。我们提出了一个新的网络，RamanU-Net，用于精确分类这些拉曼光谱。该模型对耐药和敏感大肠杆菌的平均鉴定准确率达到99.5%。我们的研究结果表明，将拉曼光镊与深度学习模型相结合，可以快速识别细菌抗生素耐药性，同时显著减少相关的时间、成本和工作量。

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引用次数: 0

Intranasal immunization with recombinant Omp34 and its derivative engineered construct, rOmp34L3×5, against Acinetobacter baumannii pulmonary infection 重组Omp34及其衍生工程构建物rOmp34L3×5鼻内免疫抗鲍曼不动杆菌肺部感染

Q2 Medicine

Medicine in Microecology

Pub Date : 2025-12-21 DOI: 10.1016/j.medmic.2025.100164

Zahra Abbasi Fashami , Abolfazl Jahangiri , Mohammadreza Jalali Nadoushan , Saeede Masoomkhani , Iraj Rasooli

The emergence of extreme and pan-drug-resistant strains of Acinetobacter baumannii has intensified the need for effective prevention strategies, including developing vaccines. This study evaluates the immunogenicity and protective efficacy of the outer membrane protein Omp34 and its engineered construct, rOmp34L3 × 5, as potential vaccine candidates against A. baumannii pulmonary infections. The recombinant proteins were expressed and purified using Ni-NTA columns. The clinical colistin-resistant strain of A. baumannii Ab/TU/ColR was used in the murine pneumonia challenge experiments. Mice were immunized intranasally with the recombinant proteins. IgG, IgA titers, and their reactivity were assessed. Bacterial challenges and survival analysis were performed. Post-challenge, bacterial burdens in organs and histopathology of the lungs were evaluated. The results demonstrated that both vaccine candidates elicited strong immune responses, particularly with significant IgA and IgG antibody production. However, immunization with rOmp34L3 × 5 showed relatively stable IgG levels over 22 weeks, whereas rOmp34 alone induced higher IgG titers. Lung, spleen, and liver cultures confirmed the effectiveness of the specific antibodies in clearing bacterial loads, with histological analysis revealing normal lung tissue in immunized mice, contrasting with severe inflammation in controls. These findings suggest that rOmp34 and rOmp34L3 × 5 have the potential to serve as effective immunogens in preventing A. baumannii infections. Nonetheless, the variability in immune response depending on the clinical strain underscores the need for further studies to optimize vaccine efficacy across diverse A. baumannii isolates.

鲍曼不动杆菌极端耐药和泛耐药菌株的出现，加强了对有效预防战略的需要，包括开发疫苗。本研究评估了外膜蛋白Omp34及其工程构建体rOmp34L3 × 5作为鲍曼不动杆菌肺部感染的潜在候选疫苗的免疫原性和保护作用。重组蛋白通过Ni-NTA柱进行表达和纯化。采用鲍曼不动杆菌临床耐粘菌素菌株Ab/TU/ColR进行小鼠肺炎攻毒实验。用重组蛋白鼻内免疫小鼠。检测IgG、IgA滴度及反应性。进行细菌挑战和生存分析。攻击后，评估器官细菌负荷和肺部组织病理学。结果表明，这两种候选疫苗都引起了强烈的免疫反应，特别是产生了显著的IgA和IgG抗体。然而，用rOmp34L3 × 5免疫22周后，IgG水平相对稳定，而单独使用rOmp34可诱导更高的IgG滴度。肺、脾和肝脏培养证实了特异性抗体在清除细菌负荷方面的有效性，组织学分析显示免疫小鼠的正常肺组织与对照组的严重炎症形成对比。这些结果表明，rOmp34和rOmp34L3 × 5有可能作为有效的免疫原预防鲍曼不动杆菌感染。尽管如此，免疫反应的可变性取决于临床菌株，强调需要进一步研究以优化不同鲍曼不动杆菌分离株的疫苗效力。

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引用次数: 0

Antimicrobial potential of Aspergillus oryzae secondary metabolites against carbapenem-resistant Klebsiella pneumoniae 米曲霉次生代谢物对耐碳青霉烯肺炎克雷伯菌的抑菌潜力

Q2 Medicine

Medicine in Microecology

Pub Date : 2025-12-16 DOI: 10.1016/j.medmic.2025.100161

Lailia Nur Rachma , Zulvikar Syambani Ulhaq

The antibacterial potential of Aspergillus oryzae (A. oryzae) EO product (AOEP) extract against Klebsiella pneumoniae (K. pneumoniae) strains BAA-1706 and BAA-1705 was investigated through minimal inhibitory concentration (MIC), biofilm inhibition assays, electron microscopy, and gene expression analysis. AOEP extract exhibited inhibitory activity with MIC₅₀ values ranging from 3.1 % to 50 % for both strains. Notably, AOEP suppressed biofilm formation at low concentrations (3.1 %–12.5 %), outperforming the positive control, kanamycin, at 6.25 %. Morphological examination revealed significant alterations upon AOEP treatment, including reduced colony size and fragmented cells, distinct from kanamycin-induced changes. qRT-PCR demonstrated that AOEP significantly downregulated key virulence genes ompA, lppA, and mrkA in strain BAA-1706, and ompA and lppA in strain BAA-1705, while pal and wzi expression remained unaffected. LC-MS/MS profiling identified several lactone-related secondary metabolites, including acyl homoserine lactone (AHL) analogs and butyrolactone I analogs, suggesting possible quorum sensing interference as a mechanism of action. These findings highlight AOEP extract as a promising multifunctional antibacterial agent that disrupts K. pneumoniae growth, biofilm formation, and virulence, with potential applications in combating antibiotic-resistant infections.

通过最小抑菌浓度（MIC）、生物膜抑制试验、电镜及基因表达分析，研究了米曲霉（Aspergillus oryzae） EO产物（AOEP）提取物对肺炎克雷伯菌（Klebsiella pneumoniae） BAA-1706和BAA-1705的抑菌活性。AOEP提取物对两种菌株的MIC50值均为3.1% ~ 50%。值得注意的是，AOEP在低浓度（3.1% - 12.5%）下抑制了生物膜的形成，优于阳性对照卡那霉素（6.25%）。形态学检查显示AOEP处理后的显著变化，包括集落大小减小和细胞碎片化，不同于卡那霉素引起的变化。qRT-PCR结果显示，AOEP显著下调菌株BAA-1706的关键毒力基因ompA、lppA和mrkA，以及菌株BAA-1705的ompA和lppA，而pal和wzi的表达未受影响。LC-MS/MS分析鉴定了几种内酯相关的次级代谢物，包括酰基高丝氨酸内酯（AHL）类似物和丁内酯I类似物，表明群体感应干扰可能是其作用机制。这些发现强调了AOEP提取物作为一种有前途的多功能抗菌剂，可以破坏肺炎克雷伯菌的生长、生物膜的形成和毒力，在对抗抗生素耐药性感染方面具有潜在的应用前景。

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引用次数: 0

Probiotic Bacillus subtilis attenuates cisplatin-induced multi-organ toxicity via redox modulation and anti-apoptotic mechanisms: Evidence from a preclinical probiotic intervention study 益生菌枯草芽孢杆菌通过氧化还原调节和抗凋亡机制减轻顺铂诱导的多器官毒性：来自临床前益生菌干预研究的证据

Q2 Medicine

Medicine in Microecology

Pub Date : 2025-12-03 DOI: 10.1016/j.medmic.2025.100160

Kusuma Kandati , Viswanath Buddolla , John Sushma Nannepaga

Background

Cisplatin, a widely used chemotherapeutic agent, is limited by dose-dependent multi-organ toxicity. Probiotic interventions have recently emerged as promising strategies to alleviate such adverse effects through antioxidative and cytoprotective mechanisms.

Methods

This preclinical study evaluated the protective effects of the spore-forming probiotic Bacillus subtilis against cisplatin-induced toxicity in female Wistar rats. Animals were assigned to control, cisplatin-only, probiotic-only, and cisplatin + probiotic groups. Biochemical indices, antioxidant enzyme activities, oxidative stress markers, and histopathological changes were systematically evaluated to determine the therapeutic efficacy of B. subtilis.

Results

Cisplatin disrupted hematological indices, altered carbohydrate and lipid metabolism, elevated oxidative stress markers (ROS, MDA), and increased DNA damage (8-OHdG) and apoptosis (caspase-3). B. subtilis supplementation restored antioxidant enzyme activities (CAT, SOD, GPx), reduced oxidative and apoptotic damage, and preserved tissue structure. These protective effects are consistent with modulation of the Nrf2/Keap1 and NF-κB pathways, suggesting enhancement of endogenous antioxidant defenses and suppression of pro-apoptotic signaling.

Conclusions

B. subtilis demonstrates potential as a safe, gut-resilient probiotic adjunct to chemotherapy, capable of mitigating systemic toxicity through redox regulation and cytoprotective mechanisms. These findings support further mechanistic and translational studies to validate probiotic-based microecological strategies in oncology care.

背景：顺铂是一种广泛使用的化疗药物，其剂量依赖性多器官毒性受到限制。最近，益生菌干预作为一种有希望的策略出现，通过抗氧化和细胞保护机制来减轻这些不良反应。方法临床前研究了产孢益生菌枯草芽孢杆菌对雌性Wistar大鼠顺铂毒性的保护作用。动物被分为对照组、单顺铂组、单益生菌组和单顺铂+益生菌组。系统评价生化指标、抗氧化酶活性、氧化应激标志物和组织病理学变化，以确定枯草芽孢杆菌的治疗效果。结果铂破坏血液学指标，改变碳水化合物和脂质代谢，升高氧化应激标志物（ROS， MDA），增加DNA损伤（8-OHdG）和细胞凋亡（caspase-3）。补充枯草芽孢杆菌可恢复抗氧化酶（CAT、SOD、GPx）活性，减轻氧化损伤和凋亡损伤，保存组织结构。这些保护作用与调节Nrf2/Keap1和NF-κB通路一致，提示内源性抗氧化防御增强和促凋亡信号抑制。枯草杆菌显示出作为一种安全的、具有肠道弹性的化疗辅助益生菌的潜力，能够通过氧化还原调节和细胞保护机制减轻全身毒性。这些发现支持进一步的机制和转化研究，以验证基于益生菌的微生态策略在肿瘤治疗中。

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引用次数: 0

Corrigendum to “Nanoparticles targeting biofilms: A new era in combating antimicrobial resistance” [Med Microecol, Volume 26, December 2025, 100156] “纳米颗粒靶向生物膜：对抗抗菌素耐药性的新时代”的勘误表[Med Microecol， vol . 26, December 2025, 100156]

Q2 Medicine

Medicine in Microecology

Pub Date : 2025-12-01 DOI: 10.1016/j.medmic.2025.100159

Amruta A. Joshi, Ravindra H. Patil

引用次数: 0

Corrigendum to “Porphyromonas gingivalis modulates E-cadherin expression: a mini-review of possible involved mechanisms” [Med Microecol 26 (2025) 100146] “牙龈卟啉单胞菌调节E-cadherin表达：可能涉及机制的迷你回顾”的更正[Med Microecol 26 (2025) 100146]

Q2 Medicine

Medicine in Microecology

Pub Date : 2025-12-01 DOI: 10.1016/j.medmic.2025.100150

Zahra Khorshidi Asl , Mahtab Mottaghi , Fatemeh Farshad , Faezeh Azmoudeh

引用次数: 0

Probiotic regulation of gut hormones following antibiotic-induced dysbiosis: Insights into host-microbiota-endocrine interactions 抗生素诱导的生态失调后益生菌对肠道激素的调节：宿主-微生物-内分泌相互作用的见解

Q2 Medicine

Medicine in Microecology

Pub Date : 2025-11-13 DOI: 10.1016/j.medmic.2025.100158

Pathipati Hareesha , Devaraju Terepogu , Gopi Krishna Pitchika , Viswanath Buddolla

Antibiotic therapy significantly disrupts the gut microbiota, leading to dysbiosis and impacting the secretion of gut hormones crucial for metabolic regulation, appetite control, and immune homeostasis. This review explores how probiotics can help restore microbial balance and modulate gut hormones, such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin, which are key regulators of metabolic processes including insulin sensitivity, glucose tolerance, fat storage, and appetite. The mechanisms involve microbial metabolite signaling, host-epithelial interactions, and communication along the gut-brain axis. The current review synthesizes information on the effects of antibiotics on the enteroendocrine network and investigates how probiotics might alleviate these disturbances through direct and microbiota-mediated pathways. Emerging technologies such as metagenomics and metabolomics are paving the way for targeted probiotic interventions. While current findings show promising potential, further rigorous clinical trials are essential to fully understand and apply these microbiome-based strategies for managing antibiotic-induced metabolic and inflammatory conditions.

抗生素治疗显著破坏肠道微生物群，导致生态失调，影响肠道激素的分泌，这些激素对代谢调节、食欲控制和免疫稳态至关重要。这篇综述探讨了益生菌如何帮助恢复微生物平衡和调节肠道激素，如胰高血糖素样肽-1 （GLP-1）、肽YY （PYY）和胃饥饿素，它们是代谢过程的关键调节因子，包括胰岛素敏感性、葡萄糖耐量、脂肪储存和食欲。其机制包括微生物代谢物信号，宿主-上皮相互作用以及肠-脑轴的通讯。本综述综合了抗生素对肠内分泌网络的影响，并探讨了益生菌如何通过直接和微生物介导的途径减轻这些干扰。宏基因组学和代谢组学等新兴技术正在为有针对性的益生菌干预铺平道路。虽然目前的研究结果显示出很大的潜力，但为了充分理解和应用这些基于微生物组的策略来管理抗生素诱导的代谢和炎症状况，进一步严格的临床试验是必不可少的。

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引用次数: 0

Gut microbiota dysbiosis and the gut–liver–brain axis: Mechanistic insights into hepatic encephalopathy 肠道菌群失调和肠-肝-脑轴：肝性脑病的机制见解

Q2 Medicine

Medicine in Microecology

Pub Date : 2025-11-01 DOI: 10.1016/j.medmic.2025.100157

Priyanka Manothiya , Debabrata Dash , Raj Kumar Koiri

Hepatic encephalopathy (HE), a severe neuropsychiatric manifestation of cirrhosis, is increasingly being understood to be intimately associated with dysbiosis of gut microbiota. The intestinal microbiota, an ever-changing consortium that performs a very critical role in the preservation of barrier function, immune homeostasis, and metabolic harmony, becomes deeply disturbed in cirrhosis. This dysregulation enhances gut permeability and enables translocation of neurotoxic metabolites like ammonia and endotoxins into systemic circulation, triggering systemic inflammation that further disrupts the blood–brain barrier and aggravates neuroinflammation beyond ammonia-mediated toxicity, accelerating hepatic decompensation and inducing neuroinflammation along the gut–liver–brain axis. This review attempts an extensive review of the changing notion regarding gut microbiota implication in HE pathogenesis. It places emphasis on mechanistic interaction among microbial dysbiosis, immune activation, and dysfunction of the central nervous system and comprehensively critiques present treatments like probiotics, prebiotics, antibiotics, and faecal microbiota transplantation (FMT). Although FMT has shown promising results in restoring microbial balance and improving neurological function, its application is limited by donor variability, procedural risks, and uncertain long-term safety. Although some clinical evidence is promising, its utility is restricted by patient-to-patient variability in microbial response, lack of beneficial biomarkers, and knowledge gaps of mechanisms. Technical innovations in metagenomics, metabolomics, and computational biology have the potential to reveal disease-specific microbial signatures and create personalized, microbiome-directed therapeutic interventions. Reestablishing microbial homeostasis is a new and potentially revolutionary treatment strategy to abrogate neuroinflammation, restore gut–liver–brain axis function, and enhance HE outcomes. This review concludes that targeting gut dysbiosis represents a paradigm shift in HE management, though personalized approaches based on a deeper mechanistic understanding are needed for future success.

肝性脑病（HE）是肝硬化的一种严重的神经精神表现，越来越多地被认为与肠道菌群失调密切相关。肠道微生物群是一个不断变化的联合体，在保护屏障功能、免疫稳态和代谢和谐中起着非常关键的作用，在肝硬化中受到严重干扰。这种失调增强了肠道通透性，使氨和内毒素等神经毒性代谢物易位进入体循环，引发全身炎症，进一步破坏血脑屏障，加重氨介导毒性以外的神经炎症，加速肝脏失代偿，并诱导沿肠-肝-脑轴的神经炎症。这篇综述试图广泛回顾关于肠道微生物群在HE发病机制中的影响的不断变化的概念。它强调微生物生态失调、免疫激活和中枢神经系统功能障碍之间的机制相互作用，并全面批评目前的治疗方法，如益生菌、益生元、抗生素和粪便微生物群移植（FMT）。尽管FMT在恢复微生物平衡和改善神经功能方面显示出有希望的结果，但其应用受到供体多样性、程序风险和不确定的长期安全性的限制。尽管一些临床证据是有希望的，但它的应用受到患者之间微生物反应的差异、缺乏有益的生物标志物和机制知识差距的限制。宏基因组学、代谢组学和计算生物学的技术创新有可能揭示疾病特异性微生物特征，并创造个性化的、微生物组导向的治疗干预措施。重建微生物稳态是一种新的、潜在的革命性治疗策略，可以消除神经炎症，恢复肠-肝-脑轴功能，提高HE预后。这篇综述的结论是，针对肠道生态失调代表了HE管理的范式转变，尽管未来的成功需要基于更深入的机制理解的个性化方法。

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引用次数: 0