洗涤菌群移植治疗伪膜性肠炎1例临床整合思维分析

正粪菌移植(fecal microbiota transplantation,FMT)治疗复发性及难治性难辨梭状芽孢杆菌感染(clostridium difficile infection,CDI)已成为共识~([1])。然而,在医学实践中,如何合理、高效应用该技术解决临床困难,所涉及的具体临床整合思维还待优化 。     

美国胃肠病学会粪菌移植国家注册局:认识微生态治疗风险和获益的重要一步

正粪菌移植(FMT)是将健康捐赠者体内获得的粪便移植入想要通过改善肠道微生态的结构和功能来缓解病情的患者体内。这种广撒网的方法对于治疗复发性艰难梭菌感染(CDI)十分有效~([1])。FMT操作简便且治疗物(如粪便)易于获取,这使得临床上重建肠道群菌的治疗进展快于科研领域。此外,过早     

粪菌移植在肠道微生态相关疾病中的应用

近年来,随着假膜性肠炎(pseudomembranous enterocolitis,PMC)、复发性难辨梭状芽孢杆菌感染(Clostridium difficile infection,CDI)等与肠道菌群失调密切相关的疾病发病率逐年升高,人们对于肠道微生物稳态的意识日益增强,并由此产生了粪菌移植(fecal microbiota transplantation,FMT)的概念。随后这项技术被迅速应用于消化系统疾病及其他系统疾病的治疗。现主要就目前FMT的技术临床应用、操作过程及并发症等问题作一概述。     

粪菌移植在治疗艰难梭菌感染中的研究进展

艰难梭菌感染(Clostridium difficile infection,CDI)是一种临床上常见的疾病,由于其明显的胃肠道症状,患者的身心健康均受到了极大的损伤。近年来,屡屡有研究证实粪菌移植(fecal microbiota transplantation,FMT)在CDI治疗中有效率较高(80%),患者的症状得到明显缓解。为了更好地服务于临床,本文将对FMT在CDI临床治疗中的进展作一概述。     

粪微生态移植治疗难辨梭状芽孢杆菌感染的研究现状

难辨梭状芽孢杆菌感染(clostridium difficile infection,CDI)是一种日益常见及严重的全球健康问题,过去通常是传统的抗生素治疗,发现往往疗效不佳,甚至会反复发生。目前粪微生态移植(fecal microbiota transplantation,FMT)开始应用于CDI的治疗且疗效良好。FMT是指将健康人的粪便中的功能菌群移植到患者胃肠道内,重建具有正常功能的肠道菌群,来实现肠道及肠道外疾病的诊疗。但目前有关FMT治疗CDI存在一些争议。     

粪菌移植的研究进展

粪菌移植(FMT)通过纠正肠道生态失衡来恢复正常肠道微生物的多样性,已在艰难梭菌感染(CDI)、炎症性肠病(IBD)、肠易激综合征(IBS)中取得确切疗效。虽然FMT广泛用于临床仍存在问题,但其发展前景广阔,值得重视和研究。该文就FMT的发展历程、临床应用以及存在的问题和展望等方面作一综述。     

粪菌移植治疗炎症性肠病的现状

炎症性肠病(inflammatory bowel disease,IBD)是常见的难治性消化系统疾病之一,其发病率和复发率逐年升高.IBD的治疗手段有限,特别是针对标准治疗方案难治的IBD治疗面临诸多棘手的问题.粪菌移植(fecal microbiota transplantation,FMT)近年来引起关注,对经标准治疗方案无法带来临床缓解的IBD显示出一定的疗效;但现阶段FMT治疗IBD的临床应用和普及仍存在许多问题.本文就FMT治疗IBD的疗效、安全性和给药方案等进行综述.     

粪菌移植治疗炎症性肠病：从免疫应答到机制

炎症性肠病(IBD)是一种慢性、复发性、非特异性炎症性肠道疾病，包括溃疡性结肠炎(UC)和克罗恩病(CD)。研究结果显示肠道菌群及其介导的免疫应答是驱动IBD发展的关键因素。目前认为粪菌移植(FMT)是治疗IBD的新型、潜力巨大的有效方法，但机制不明。本文就FMT在IBD中的应用现状、FMT治疗IBD后免疫应答反应及其菌群-免疫相互作用机制作一综述，以期探讨FMT治疗IBD的潜在机制。     

将标准化粪菌移植推向主流

粪菌移植（fecal microbiota transplantation，FMT）在世界医学史上至少始于公元4世纪，但是直到近几年才得到了前所未有的快速发展。2013年，FMT首次被写入美国医学指南，用于复发性难辨梭状芽孢杆菌感染（clostridium difficile infection，CDI）的治疗”。同时，其在国内外用于炎症性肠病、肠易激综合征、代谢综合征等肠内外疾病的治疗，也已引起广泛关注。本文主要讨论FMT的医学史、概念转化、现状和发展方向。     

粪菌移植治疗溃疡性结肠炎的疗效及其相关因素分析

背景:目前粪菌移植(FMT)已成为治疗某些复杂肠道疾病的新方法,对艰难梭菌感染(CDI)的疗效显著。目的:系统评价FMT治疗溃疡性结肠炎(UC)的疗效及其可能的影响因素。方法:计算机检索Pub Med、Medline、Embase、中国知网、中文科技期刊全文数据库,纳入FMT治疗UC的临床试验。采用Rev Man 5. 3软件对纳入的随机对照试验(RCTs)行meta分析,采用单个率meta分析评估不同因素对FMT疗效的影响。结果:共纳入11篇文献,包括4篇RCTs和7篇非RCTs。RCTs行meta分析发现,FMT治疗UC的临床缓解率和有效率均显著高于对照组(OR=2. 89,95%CI:1. 70～4. 92,P 0. 000 01;OR=2. 70,95%CI:1. 31～5. 57,P=0. 007)。单个率meta分析显示,下消化道移植组的临床缓解率显著高于上消化道移植组(39%对19%,P=0. 037),而不同供体选择组别之间无明显差异(P=0. 967)。结论:FMT可有效治疗UC,经下消化道途径移植的效果较好,无特定供体群体选择。     

Recurrent Clostridium difficile infections: The importance of the intestinal microbiota

Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability.     

Fecal microbiota transplantation for management of Clostridium difficile infection

The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.     

Gastrointestinal dysbiosis and the use of fecal microbial transplantation in Clostridium difficile infection

The impact of antibiotics on the human gut microbiota is a significant concern. Antibiotic-associated diarrhea has been on the rise for the past few decades with the increasing usage of antibiotics. Clostridium difficile infections (CDI) have become one of the most prominent types of infectious diarrheal disease, with dramatically increased incidence in both the hospital and community setting worldwide. Studies show that variability in the innate host response may in part impact upon CDI severity in patients. That being said, CDI is a disease that shows the most prominent links to alterations to the gut microbiota, in both cause and treatment. With recurrence rates still relatively high, it is important to explore alternative therapies to CDI. Fecal microbiota transplantation (FMT) and other types of bacteriotherapy have become exciting avenues of treatment for CDI. Recent clinical trials have generated excitement for the use of FMT as a therapeutic option for CDI; however, the exact components of the human gut microbiota needed for protection against CDI have remained elusive. Additional investigations on the effects of antibiotics on the human gut microbiota and subsequent CDI will help reduce the socioeconomic burden of CDI and potentially lead to new therapeutic modalities.     

High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria

Fecal microbiota transplantation (FMT) is becoming a more widely used technology for treatment of recurrent Clostridum difficile infection (CDI). While previous treatments used fresh fecal slurries as a source of microbiota for FMT, we recently reported the successful use of standardized, partially purified and frozen fecal microbiota to treat CDI. Here we report that high-throughput 16S rRNA gene sequencing showed stable engraftment of gut microbiota following FMT using frozen fecal bacteria from a healthy donor. Similar bacterial taxa were found in post-transplantation samples obtained from the recipients and donor samples, but the relative abundance varied considerably between patients and time points. Post FMT samples from patients showed an increase in the abundance of Firmicutes and Bacteroidetes, representing 75–80% of the total sequence reads. Proteobacteria and Actinobacteria were less abundant (< 5%) than that found in patients prior to FMT. Post FMT samples from two patients were very similar to donor samples, with the Bacteroidetes phylum represented by a great abundance of members of the families Bacteroidaceae, Rikenellaceae and Porphyromonadaceae, and were largely comprised of Bacteroides, Alistipes and Parabacteroides genera. Members of the phylum Firmicutes were represented by Ruminococcaceae, Lachnospiraceae, Verrucomicrobiaceae and unclassified Clostridiales and members of the Firmicutes. One patient subsequently received antibiotics for an unrelated infection, resulting in an increase in the number of intestinal Proteobacteria, primarily Enterobacteriaceae. Our results demonstrate that frozen fecal microbiota from a healthy donor can be used to effectively treat recurrent CDI resulting in restoration of the structure of gut microbiota and clearing of Clostridum difficile.     

Restoring the gut microbiome for the treatment of inflammatory bowel diseases

Fecal microbiota transplantation(FMT)is considered to be a highly successful therapy for recurrent and refractory Clostridium difficile infection(CDI)based on recent clinical trials.The pathogenesis of inflammatory bowel diseases(IBD)is thought to be due in part to perturbations in the gut microflora that disrupt homeostasis.FMT restores essential components of the microflora which could reverse the inflammatory processes observed in IBD.Case reports and series for the treatment of IBD by FMT have shown promise with regards to treatment success and safety despite the limitations of the reporting.Future studies will determine the optimal delivery and preparation of stool as well as the conditions under which the recipient will derive maximal benefit.The long term consequences of FMT with regards to infection,cancer,auto-immune,and metabolic diseases are not known and will require continued regulation and study.Despite these limitations,FMT may be beneficial for the treatment of ulcerative colitis and Crohn’s disease,particularly those with concurrent CDI or with pouchitis.     

Maintaining standard volumes,efficacy and safety,of fecal microbiota transplantation for C. difficile infection during the COVID-19 pandemic: A prospective cohort study

BackgroundFecal microbiota transplantation (FMT) can be a life-saving treatment against recurrent Clostridioides difficile infection (CDI). It is therefore necessary to maintain this procedure available for these patients during the COVID-19 pandemic while keeping high efficacy and safety standards.AimsTo report outcomes of a FMT service that has adapted its operational workflow during COVID-19 pandemic to continue offering FMT to patients with CDI.MethodsAll patients with CDI referred to our center for FMT during pandemic were prospectively included. Each step of the FMT working protocol was adapted with specific security measures to prevent the transmission of SARS-CoV-2.ResultsOf 26 patients evaluated for FMT, 21 were treated for recurrent or refractory CDI. Eighteen patients completed the 8-week follow-up, and no one recurred after FMT. Follow-up is ongoing in 3 patients, although in all of them diarrhea disappeared after the first procedure. No serious adverse events were reported. Two patients had also COVID-19-related pneumonia, and were cured both from CDI and COVID-19.ConclusionThis is the first report to show that it is possible to maintain standard volumes, efficacy and safety of FMT for recurrent CDI during the COVID-19 pandemic, by adopting specific changes in the operational workflow.     

Outcomes of Fecal Microbiota Transplantation for Clostridium difficile Infection in Patients with Inflammatory Bowel Disease

Digestive Diseases and Sciences - Fecal microbiota transplantation (FMT) has recently been shown to be a promising therapy for recurrent and refractory Clostridium difficile infections (CDI)...     

Faecal microbiota transplantation for recurrent Clostridioides difficile infection: an Australian experience − effective,safe, yet room for improvement

Faecal microbiota transplantation (FMT) is reportedly effective and safe for the management of recurrent or refractory Clostridioides difficile infection (CDI), yet real‐world data of outcomes of FMT in Australia are limited. In this series, FMT safely resulted in resolution of CDI in 19 patients with reduced healthcare utilisation after 25 FMT, but one patient was diagnosed with an anti‐nuclear antibody‐positive constitutional illness and Hashimoto thyroiditis following FMT. Further prospective evaluation of the utility of FMT earlier in CDI treatment algorithms to minimise cost and morbidity, and recipient follow up for immune‐mediated conditions, is required.     

Therapies to modulate gut microbiota:Past,present and future

The human gut microbiota comprises of a complex and diverse array of microorganisms,and over the years the interaction between human diseases and the gut microbiota has become a subject of growing interest.Disturbed microbial milieu in the gastrointestinal tract is central to the pathogenesis of several diseases including antibiotic-associated diarrhea and Clostridioides difficile infection(CDI).Manipulation of this microbial milieu to restore balance by microbial replacement therapies has proven to be a safe and effective treatment for recurrent CDI.There is considerable heterogeneity in various aspects of stool processing and administration for fecal microbiota transplantation(FMT)across different centers globally,and standardized microbioal replacement therapies offer an attractive alternative.The adverse effects associated with FMT are usually mild.However,there is paucity of data on long term safety of FMT and there is a need for further studies in this regard.With our increasing understanding of the host-microbiome interaction,there is immense potential for microbial replacement therapies to emerge as a treatment option for several diseases.The role of microbioal replacement therapies in diseases other than CDI is being extensively studied in ongoing clinical trials and it may be a potential treatment option for inflammatory bowel disease,irritable bowel syndrome,obesity,multidrug resistant infections,and neuropsychiatric illnesses.Fecal microbiota transplantation for non-CDI disease states should currently be limited only to research settings.     

Characteristics and management of children with Clostridioides difficile infection at a tertiary pediatric hospital in China

BackgroundClostridiodes difficile infection (CDI) is one of the most common causes of antibiotic-associated diarrhea in children. Conventional antibiotics and emerging fecal microbiota transplantation (FMT) are used to treat CDI.MethodsChildren with CDI admitted to the Shanghai Children's Hospital, from September 2014 to September 2020, were retrospectively included to this observational study. Pediatric patients were assigned as initial CDI and recurrent CDI (RCDI), and symptoms, comorbidities, imaging findings, laboratory tests, and treatments were systematically recorded and analyzed.ResultsOf 109 pediatric patients with CDI, 58 were boys (53.2%), and the median age was 5 years (range, 2-9 years). The main clinical symptoms of CDI children were diarrhea (109/109, 100%), hematochezia (55/109, 50.46%), abdominal pain (40/109, 36.70%); fever, pseudomembrane, vomit, and bloating were observed in 39 (35.78%), 33 (30.28%), and 24 (22.02%) patients, respectively. For the primary therapy with conventional antibiotics, 68 patients received metronidazole, and 41 patients received vancomycin. RCDI occurred in 48.53% (33/68) of those initially treated with metronidazole compared with 46.33% (19/41) of those initially treated with vancomycin (p=0.825). The total resolution rate of FMT for RCDI children was significantly higher than with vancomycin treatment (28/29, 96.55% vs 11/23, 47.83%, p < 0.001). There were no serious adverse events (SAEs) reported after two months of FMT.ConclusionsThe major manifestations of children with CDI were diarrhea, hematochezia, and abdominal pain. The cure rate of FMT for pediatric RCDI is superior to vancomycin treatment.