Microbiota transplantation

微生物移植
  • 文章类型: Journal Article
    在尖端测序方法和全球努力的时代,如人类微生物组项目和MetaHIT,人类微生物组是一个复杂多样的微生物群落。当前科学研究的中心主题围绕着恢复平衡的微生物组成,被称为“优生物”,“作为治疗各种疾病的有针对性的方法。阴道微生物移植(VMT),受粪便微生物移植成功的启发,通过从健康供体转移完整的微生物群来解决阴道菌群失调的创新疗法。抗生素,虽然有效,带来不利影响的挑战,高复发率,以及对有益乳酸菌菌株的潜在危害。持续使用抗生素也引发了人们对耐药菌株发展的担忧。益生菌,虽然显示出希望,在治疗多因素疾病方面表现出不一致,并担心它们是否适合不同的遗传背景。鉴于与抗生素和益生菌治疗相关的经常性挑战,VMT作为一种必要的替代方案出现,提供了一个独特的和有前途的途径,有效和可靠地管理阴道菌群失调的大多数妇女。这篇综述批判性地评估了动物和人类研究的结果,为VMT的功效和挑战提供细致入微的见解。对临床试验的广泛分析,提供了正在进行和已完成的试验的当前概述,揭示VMT不断发展的临床景观和治疗潜力。深入研究起源,机制,和优化的VMT协议,该综述强调了持续的研究努力以推进这一开创性的妇科治疗的必要性.
    In an age of cutting-edge sequencing methods and worldwide endeavors such as The Human Microbiome Project and MetaHIT, the human microbiome stands as a complex and diverse community of microorganisms. A central theme in current scientific inquiry revolves around reinstating a balanced microbial composition, referred to as \"eubiosis,\" as a targeted approach for treating vast array of diseases. Vaginal Microbiota Transplantation (VMT), inspired by the success of fecal microbiota transplantation, emerges as an innovative therapy addressing vaginal dysbacteriosis by transferring the complete microbiota from a healthy donor. Antibiotics, while effective, pose challenges with adverse effects, high recurrence rates, and potential harm to beneficial Lactobacillus strains. Continued antibiotic usage also sparks worries regarding the development of resistant strains. Probiotics, though showing promise, exhibit inconsistency in treating multifactorial diseases, and concerns linger about their suitability for diverse genetic backgrounds. Given the recurrent challenges associated with antibiotic and probiotic treatments, VMT emerges as an imperative alternative, offering a unique and promising avenue for efficiently and reliably managing vaginal dysbiosis among a majority of women. This review critically evaluates findings from both animal and human studies, offering nuanced insights into the efficacy and challenges of VMT. An extensive analysis of clinical trials, provides a current overview of ongoing and completed trials, shedding light on the evolving clinical landscape and therapeutic potential of VMT. Delving into the origins, mechanisms, and optimized protocols of VMT, the review underscores the imperative for sustained research efforts to advance this groundbreaking gynecological therapy.
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  • 文章类型: Journal Article
    背景:口腔内口臭(IOH)是口腔局部产生的除全身性疾病外的口臭,是现代社会人际交往和心理障碍的主要原因之一。然而,目前的治疗方式仍然只能缓解IOH,不能根除它。因此,基于IOH患者口腔微生态的差异表现,我们提出了一种旨在恢复口腔微生态平衡的微生物移植治疗方法,并通过Wistar大鼠口腔菌群定植试验分析了其可行性。
    目的:收集IOH患者和健康受试者的唾液菌群样本,通过Wistar大鼠口腔菌群定植试验,分析口腔菌群移植(OMT)治疗IOH的可行性。
    方法:随机选择2017年6月至2022年6月在新疆医科大学第一附属医院就诊的7例以口臭为主诉的IOH患者和3例健康体检者。使用Halimeter便携式呼吸检测器来记录呼吸值并收集唾液菌群样品。将16只SPF级雄性Wistar大鼠圈养在新疆医科大学动物实验中心,随机分为实验组(E组)和对照组(C组)进行口腔菌群定植试验。使用16SrRNA测序技术和PICRUSt代谢分析在Wistar大鼠测试期间口腔菌群的物种组成和相关代谢分析。此外,在测试过程中记录大鼠呼吸值的变化。
    结果:卟啉的比例,梭杆菌,Leptotrichia,在IOH患者唾液菌群定植后,E组肽链球菌明显高于C组(均P<0.05),在定殖之前,Gemella的丰度为零,与基线相比,C组未见定植。PICRUSt代谢分析也显示E组定植后IOH相关代谢途径显著增强(均P<0.05),以及显著高于基线和C组的呼吸值(所有P<0.0001)。在健康受试者的唾液菌群定植后,E组大鼠显示相关的引起气味的细菌定植的丰度减少,相关新陈代谢的减少,呼吸值显着下降。相比之下,在IOH患者唾液菌群定植后,与基线相比,C组还显示菌群结构和呼吸值的差异变化。
    结论:用于IOH的OMT是一种有前途的绿色治疗选择,但环境因素和个体差异的影响仍然不容忽视。
    BACKGROUND: Intra-oral halitosis (IOH) is bad breath produced locally by the mouth in addition to systemic diseases and is one of the main causes of interpersonal communication and psychological disorders in modern society. However, current treatment modalities still only alleviate IOH and do not eradicate it. Therefore, based on the differential performance of oral microecology in IOH patients, we propose a microbiota transplantation treatment aimed at restoring oral microecological balance and analyze its feasibility by oral flora colonization test in Wistar rats.
    OBJECTIVE: Saliva flora samples were collected from IOH patients and healthy subjects to analyze the feasibility of oral microbiota transplantation (OMT) for the treatment of IOH by the Wistar rat oral flora colonization test.
    METHODS: Seven patients with IOH who visited the First Affiliated Hospital of Xinjiang Medical University from June 2017 to June 2022 with the main complaint of halitosis and three healthy subjects were randomly selected. A Halimeter portable breath detector was used to record breath values and collect saliva flora samples. Sixteen SPF-grade male Wistar rats were housed in the Animal Experiment Center of Xinjiang Medical University and randomly divided into an experimental group (Group E) and a control group (Group C) for the oral flora colonization test. Species composition and associated metabolic analysis of oral flora during the Wistar rat test using 16SrRNA sequencing technology and PICRUSt metabolic analysis. Also, the changes in the breath values of the rats were recorded during the test.
    RESULTS: The proportion of Porphyromonas, Fusobacterium, Leptotrichia, and Peptostreptococcus was significantly higher in group E compared to group C after colonization of salivary flora of IOH patients (all P < 0.05), and the abundance with Gemella was zero before colonization, while no colonization was seen in group C after colonization compared to baseline. PICRUSt metabolic analysis also showed significantly enhanced IOH-related metabolic pathways after colonization in group E (all P < 0.05), as well as significantly higher breath values compared to baseline and group C (all P < 0.0001). After colonization by salivary flora from healthy subjects, group E rats showed a decrease in the abundance of associated odor-causing bacteria colonization, a reduction in associated metabolism, and a significant decrease in breath values. In contrast, group C also showed differential changes in flora structure and breath values compared to baseline after salivary flora colonization of IOH patients.
    CONCLUSIONS: OMT for IOH is a promising green treatment option, but the influence of environmental factors and individual differences still cannot be ignored.
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  • 文章类型: Journal Article
    剖腹产对于降低孕产妇和新生儿死亡率至关重要,但其副作用之一可能是分娩过程中母婴微生物群垂直传播的中断,可能导致剖腹产婴儿肠道菌群失调和疾病风险增加。为了解决这种生态失调,在剖腹产过程中补充“缺少什么”似乎是合理的。这个想法促使了一些临床试验,包括概念验证,调查阴道微生物接种等干预措施,口服母体阴道微生物,甚至口服母体粪便。特此,我们总结了这些试验,以帮助了解这些研究的现状,强调大多数这些研究的主要试点性质,并强调需要精心设计的更大样本的研究,以指导未来的循证医学。
    剖腹产与CS婴儿的肠道菌群失调有关,并增加从儿童到成年的疾病风险。除了使用传统的益生菌来恢复CS相关的菌群失调,一个新的研究方向是探讨模拟自然接种过程缓解婴儿肠道菌群失调的潜力。一些小规模研究表明,移植母体阴道甚至粪便微生物群可能会恢复CS相关的婴儿菌群失调。关于临床适用性仍然存在争议,安全,这些方法的功效和机制。
    C-section is crucial in reducing maternal and neonatal mortality when medically indicated, but one of its side effects could be the disruption of vertical transmission of maternal-infant microbiota during delivery, potentially leading to gut dysbiosis and increased disease risks in C-section infants. To address such dysbiosis, it seems reasonable to supplement \"what is missing\" during C-section procedure. This idea has prompted several clinical trials, including proof-of-concept, investigating interventions like vaginal microbial seeding, oral administration of maternal vaginal microbes and even oral administration of maternal fecal materials. Hereby, we have summarized these trials to help understand the current state of these researches, highlighting the predominantly pilot nature of most of these studies and emphasizing the need for well-designed studies with larger sample to guide evidence-based medicine in the future.
    C-section is associated with gut dysbiosis in CS infants and increased disease risks from childhood to adulthood.Apart from using traditional probiotics to restore CS-related dysbiosis, a new research direction is to investigate the potential of mimicking natural inoculation process would alleviate infant gut dysbiosis.Several small-scale studies have shown that transplanting maternal vaginal or even fecal microbiota might restore CS-related infant dysbiosis. Controversy remains regarding the clinical applicability, safety, efficacy and mechanisms of these approaches.
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  • 文章类型: Systematic Review
    牙周炎是一种与牙龈下微生物组严重菌群失调有关的疾病。牙周炎的治疗旨在将菌群失调环境转变为共生环境。我们假设口腔微生物群移植可以导致牙周炎的显着改善。因此,本研究的目的是确定牙周炎患者标准牙周治疗后微生物移植的有效性。通过使用布尔术语“AND”组合关键字来执行搜索策略,这是“牙周炎和微生物移植”。由于研究资源有限,我们在本系统综述中纳入了体外和体内研究.QUIN偏倚风险工具用于评估体外研究中的偏倚风险。而SYRCLE的偏倚风险评估用于体内研究。口腔微生物移植(OMT)已显示出治疗牙周炎的潜力。OMT显着减少牙周炎相关的病原微生物种类(P。牙髓,中间介体普雷沃特拉,T.Vincentii,卟啉单胞菌sp.)和增加的有益细菌(P.黑色素,具核梭杆菌,P.catonium,Capnocytophagaochracea,C.sputigena,C.牙龈,副流感嗜血杆菌,和伸长奈瑟球菌)在体外测试中。此外,在体内测试中,与全口机械清创和抗菌清创相比,单一辅助OMT对口腔微生物群组成也有影响。OMT在解决高风险人群方面可能更便宜,更有效。目前,由于缺乏可用信息,因此无法提供OMT临床建议.在纳入人体临床试验之前,这种治疗需要进行更多的安全性和有效性测试。
    Periodontitis is a disease linked to severe dysbiosis of the subgingival microbiome. The treatment of periodontitis aims to change the dysbiosis environment to a symbiosis environment. We hypothesized that oral microbiota transplantation can lead to a significant improvement in periodontitis. Therefore, the aim of this study was to determine the effectiveness of microbiota transplantation after standard periodontal treatment in periodontitis patients. The search strategy was carried out by using the Boolean term \"AND\" to combine the keywords, which were \"periodontitis AND microbiota transplantation\". Due to the limited resources of the study, we included both in vitro and in vivo investigations in this systematic review. The QUIN risk of bias tool was employed to assess the risk of bias in in vitro studies, while SYRCLE\'s risk of bias assessment was used for in vivo studies. Oral microbiota transplants (OMTs) have shown potential in treating periodontitis. OMTs significantly reduced periodontitis-associated pathogenic microbial species (P. endodontalis, Prevotella intermedia, T. vincentii, Porphyromonas sp.) and increased beneficial bacteria (P. melaninogenica, Fusobacterium nucleatum, P. catoniae, Capnocytophaga ochracea, C. sputigena, C. gingivalis, Haemophilus parainfluenzae, and Neisseria elongata) upon in vitro testing. Furthermore, in the in vivo tests, single adjunctive OMT also had an effect on the oral microbiota composition compared to the full-mouth mechanical and antimicrobial debridement. OMTs may be cheaper and more effective at addressing high-risk individuals. At present, it is not possible to provide OMT clinical advice due to the lack of available information. This treatment needs to be subjected to more safety and efficacy testing before being included human clinical trials.
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  • 文章类型: Journal Article
    阴道微生物群在女性生殖健康中起着至关重要的作用,被认为是预测疾病结果和个性化测试的生物标志物。然而,其与人乳头瘤病毒(HPV)感染和宫颈癌的关系尚不清楚。因此,本文对阴道微生物群之间的关联进行了综述,HPV感染,还有宫颈癌.我们讨论了阴道微生物群的组成,它的生态失调,及其与HPV感染的关系,以及宫颈癌发展的潜在机制。此外,我们评估了益生菌和阴道微生物移植等治疗策略在预防和治疗HPV感染和宫颈癌相关疾病方面的可行性.在未来,仍然需要进行广泛的复制研究,以更深入地了解阴道微生物群之间的复杂关系,HPV感染,还有宫颈癌,并阐明阴道微生物群作为预测疾病结局的潜在生物标志物的作用,从而为个性化测试提供理论依据。
    The vaginal microbiota plays a crucial role in female reproductive health and is considered a biomarker for predicting disease outcomes and personalized testing. However, its relationship with human papillomavirus (HPV) infection and cervical cancer is not yet clear. Therefore, this article provides a review of the association between the vaginal microbiota, HPV infection, and cervical cancer. We discuss the composition of the vaginal microbiota, its dysbiosis, and its relationship with HPV infection, as well as potential mechanisms in the development of cervical cancer. In addition, we assess the feasibility of treatment strategies such as probiotics and vaginal microbiota transplantation to modulate the vaginal microbiota for the prevention and treatment of diseases related to HPV infection and cervical cancer. In the future, extensive replication studies are still needed to gain a deeper understanding of the complex relationship between the vaginal microbiota, HPV infection, and cervical cancer, and to clarify the role of the vaginal microbiota as a potential biomarker for predicting disease outcomes, thus providing a theoretical basis for personalized testing.
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  • 文章类型: Journal Article
    粪便微生物移植(FMT)是一种将粪便细菌从健康供体转移到患者肠道以恢复肠道免疫稳态的过程。虽然FMT主要用于治疗胃肠道疾病,如炎症性肠病和肠易激综合征,尤其是艰难梭菌感染(目前唯一用作临床治疗),但最近的研究表明,它也可能成为妇科疾病的潜在治疗方法。包括子宫内膜异位症和多囊卵巢综合征(PCOS)。相反,与FMT方法相比,阴道微生物群移植(VMT)是一种更新且较少使用的方法,其潜在应用仍在探索中。它涉及将健康女性的整个阴道微生物群直接移植到患者的阴道中,以轻松重建局部微生物群环境,恢复阴道优生和缓解症状。像FMT一样,VMT被认为具有治疗不同微生物群相关病症的潜力。事实上,许多妇科疾病,如细菌性阴道病和外阴阴道念珠菌病,被认为是由阴道微生物群的不平衡引起的。在这次审查中,我们将总结发展,当前的挑战,以及未来微生物移植的前景,目的是探索新策略,将其作为治疗广泛妇科疾病的有希望的途径。
    Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients\' intestines to restore gut-immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome-and especially Clostridium difficile infection (currently the only used as clinical treatment)-recent research has suggested that it may also become a potential treatment for gynecological disorders, including endometriosis and polycystic ovary syndrome (PCOS). On the contrary, vaginal microbiota transplantation (VMT) is a newer and less commonly used procedure than the FMT approach, and its potential applications are still being explored. It involves direct grafting of the entire vaginal microbiota of healthy women into the vaginal tract of patients to easily rebuild the local microbiota environment, restoring vaginal eubiosis and relieving symptoms. Like FMT, VMT is thought to have potential in treating different microbiota-related conditions. In fact, many gynecological disorders, such as bacterial vaginosis and vulvovaginal candidiasis, are thought to be caused by an imbalance in the vaginal microbiota. In this review, we will summarize the development, current challenges, and future perspectives of microbiota transplant, with the aim of exploring new strategies for its employment as a promising avenue for treating a broad range of gynecological diseases.
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  • 文章类型: Journal Article
    非酒精性脂肪性肝病(NAFLD)是代谢功能障碍的肝脏表现,缺乏有效的干预措施。研究抗性淀粉(RS)作为微生物群导向的膳食补充剂治疗NAFLD的效果。我们将一项针对NAFLD患者的4个月随机安慰剂对照临床试验(ChiCTR-IOR-15007519)与宏基因组学和代谢组学分析相结合.相对于对照(n=97),RS干预(n=99)导致肝内甘油三酯含量(IHTC)的9.08%绝对减少,在调整体重减轻后为5.89%。血清支链氨基酸(BCAAs)和肠道微生物种类,特别是杆状拟杆菌,与IHTC和肝酶显着相关,并被RS降低。多组学整合分析揭示了肠道微生物群变化之间的相互作用,BCAA可用性,和肝脏脂肪变性,因果关系由粪便微生物群移植和小鼠单菌落化支持。因此,RS膳食补充可能是通过改变肠道微生物群组成和功能来管理NAFLD的策略。
    Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic dysfunction for which effective interventions are lacking. To investigate the effects of resistant starch (RS) as a microbiota-directed dietary supplement for NAFLD treatment, we coupled a 4-month randomized placebo-controlled clinical trial in individuals with NAFLD (ChiCTR-IOR-15007519) with metagenomics and metabolomics analysis. Relative to the control (n = 97), the RS intervention (n = 99) resulted in a 9.08% absolute reduction of intrahepatic triglyceride content (IHTC), which was 5.89% after adjusting for weight loss. Serum branched-chain amino acids (BCAAs) and gut microbial species, in particular Bacteroides stercoris, significantly correlated with IHTC and liver enzymes and were reduced by RS. Multi-omics integrative analyses revealed the interplay among gut microbiota changes, BCAA availability, and hepatic steatosis, with causality supported by fecal microbiota transplantation and monocolonization in mice. Thus, RS dietary supplementation might be a strategy for managing NAFLD by altering gut microbiota composition and functionality.
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  • 文章类型: Journal Article
    大约60-80%的接受腹骨盆放射疗法治疗的癌症患者遭受放射疗法后的毒性,包括放射性肠病和骨髓抑制。对于这种辐射损伤缺乏有效的预防和治疗策略。肠道微生物群对于加深我们对辐射损伤发病机理的理解具有很高的研究价值,特别是放射性肠病,它类似于炎症性肠病的病理生理学,并通过为癌症患者提供更安全的治疗来促进个性化医疗。临床前和临床数据一致支持肠道微生物群成分,包括乳酸生产者,SCFA生产者,吲哚化合物生产者和Akkermansia施加肠道和造血放射性保护。这些特征可作为辐射损伤的潜在预测生物标志物,与微生物多样性一起,这有力地预测了多种类型癌症的放疗后毒性。相应开发的操作策略,包括选择性微生物群移植,益生菌,纯化的功能性代谢物和微生物-宿主相互作用途径的配体是有前途的放射保护剂和放射缓解剂,值得在临床试验中进行广泛验证。随着大规模的机械研究和初步临床试验加强其转化价值,肠道微生物群可能会提高预测,预防和减轻辐射伤害。在这次审查中,我们总结了与无线电保护相关的最先进的里程碑研究,为肿瘤学家提供启发性的见解,胃肠病学家和实验室科学家对这种被忽视的复杂疾病感兴趣。
    Approximately 60-80% of cancer patients treated with abdominopelvic radiotherapy suffer post-radiotherapy toxicities including radiation enteropathy and myelosuppression. Effective preventive and therapeutic strategies are lacking for such radiation injury. The gut microbiota holds high investigational value for deepening our understanding of the pathogenesis of radiation injury, especially radiation enteropathy which resembles inflammatory bowel disease pathophysiology and for facilitating personalized medicine by providing safer therapies tailored for cancer patients. Preclinical and clinical data consistently support that gut microbiota components including lactate-producers, SCFA-producers, indole compound-producers and Akkermansia impose intestinal and hematopoietic radio-protection. These features serve as potential predictive biomarkers for radiation injury, together with the microbial diversity which robustly predicts milder post-radiotherapy toxicities in multiple types of cancer. The accordingly developed manipulation strategies including selective microbiota transplantation, probiotics, purified functional metabolites and ligands to microbe-host interactive pathways are promising radio-protectors and radio-mitigators that merit extensive validation in clinical trials. With massive mechanistic investigations and pilot clinical trials reinforcing its translational value the gut microbiota may boost the prediction, prevention and mitigation of radiation injury. In this review, we summarize the state-of-the-art landmark researches related with radio-protection to provide illuminating insights for oncologists, gastroenterologists and laboratory scientists interested in this overlooked complexed disorder.
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  • 文章类型: Journal Article
    炎症性肠病代表一系列复杂的疾病,其病因尚不完全清楚,导致胃肠道慢性炎症。在炎症性肠病中,一种有前途的治疗方法是粪便微生物移植(FMT),近年来,FMT对复发性CDI的有效性和安全性越来越高;此外,它在治疗SARS-CoV-2和CDI合并感染方面显示出真正的临床益处。克罗恩病和溃疡性结肠炎的特点是免疫失调,导致消化道损伤引起的免疫反应。大多数目前的治疗策略与高成本和许多副作用有关,直接针对免疫反应。因此,通过FMT改变微生物环境提供了一种替代方法,可以以安全的方式间接影响宿主的免疫系统。研究概述了FMT患者与对照组的UC和CD的内镜和临床改善。这篇综述概述了FMT在IBD病例中通过改善患者不平衡的肠道,因此改善内窥镜和临床症状学。我们旨在强调FMT的临床重要性和益处,以预防IBD的耀斑或并发症,并强调需要进一步验证以建立IBD中FMT的临床方案。
    Inflammatory bowel diseases represent a complex array of diseases of incompletely known etiology that led to gastrointestinal tract chronic inflammation. In inflammatory bowel disease, a promising method of treatment is represented by fecal microbiota transplantation (FMT), FMT has shown its increasing effectiveness and safety in recent years for recurrent CDI; moreover, it showed real clinical benefits in treating SARS-CoV-2 and CDI co-infection. Crohn\'s disease and ulcerative colitis are characterized by immune dysregulation, resulting in digestive tract damage caused by immune responses. Most current therapeutic strategies are associated with high costs and many adverse effects by directly targeting the immune response, so modifying the microbial environment by FMT offers an alternative approach that could indirectly influence the host\'s immune system in a safe way. Studies outline the endoscopic and clinical improvements in UC and CD in FMT patients versus control groups. This review outlines the multiple benefits of FMT in the case of IBD by improving patients unbalanced gut, therefore improving endoscopic and clinical symptomatology. We aim to emphasize the clinical importance and benefits of FMT in order to prevent flares or complications of IBD and to highlight that further validation is needed for establishing a clinical protocol for FMT in IBD.
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  • 文章类型: Journal Article
    肠道菌群失衡与结直肠癌(CRC)发生和发展的相关性已变得清晰。这项工作研究了二甲双胍对小鼠肠道菌群和CRC发生的影响。从健康对照(HC)供体和CRC患者收集人粪便样品。与HC捐赠者相比,CRC患者的肠道菌群丰度降低;然而,他们增加了大量有害的拟杆菌。小鼠注射偶氮甲烷(AOM)以诱导结肠直肠肿瘤发生模型。治疗CRC患者来源的粪便菌群促进肿瘤发生,它增加了Ki67,β-catenin的表达,小鼠结肠组织中的COX-2和CyclinD1。二甲双胍的进一步治疗阻断小鼠结肠直肠肿瘤发生。收集二甲双胍治疗小鼠的粪便微生物群,它显示了减少的拟杆菌丰度,并抑制了AOM诱导的小鼠结直肠肿瘤发生。此外,二甲双胍修饰的微生物群促进小鼠结肠组织中M1巨噬细胞相关标志物IL-6和iNOS,但抑制M2巨噬细胞相关标志物IL-4R和Arg1。总之,本研究提示二甲双胍介导的肠道菌群改变抑制巨噬细胞M2极化,从而阻断结直肠肿瘤发生.
    The correlation of imbalanced gut microbiota with the onset and progression of colorectal cancer (CRC) has become clear. This work investigates the effect of metformin on gut microbiota and genesis of CRC in mice. Human fecal samples were collected from healthy control (HC) donors and CRC patients. Compared to HC donors, CRC patients had reduced abundance of gut microbiota; however, they had increased abundance of detrimental Bacteroidetes. Mice were injected with azomethane (AOM) to induce colorectal tumorigenesis models. Treatment of CRC patients-sourced fecal microbiota promoted tumorigenesis, and it increased the expression of Ki67, β-catenin, COX-2, and Cyclin D1 in mouse colon tissues. Further treatment of metformin blocked the colorectal tumorigenesis in mice. Fecal microbiota from the metformin-treated mice was collected, which showed decreased Bacteroidetes abundance and suppressed AOM-induced colorectal tumorigenesis in mice as well. Moreover, the metformin- modified microbiota promoted the M1 macrophage-related markers IL-6 and iNOS but suppressed the M2 macrophage-related markers IL-4R and Arg1 in mouse colon tissues. In conclusion, this study suggests that metformin-mediated gut microbiota alteration suppresses macrophage M2 polarization to block colorectal tumorigenesis.
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