Fecal microbiota transplantation for Clostridium difficile infection in Taiwan: Establishment and implementation

Clostridium difficile infection (CDI) remains a major public health issue, and fecal microbiota transplantation (FMT) has become one of the standard therapies for recurrent or refractory CDI. When compared to medical therapies, such as metronidazole or vancomycin, FMT has a high rate of treatment response with acceptable safety and efficiency. Following promulgation of the amendments in September 2018 in Taiwan, FMT has been indicated for recurrent or refractory CDI. The Taiwan Microbiota Consortium contributed to the Taiwan FMT Expert Consensus, which established basic norms and stipulated essential principles, including the indications for transplantation, eligible locations and personnel, donor screening policies, fecal sample handling, and post-FMT follow-up. However, establishing an eligible FMT team in a qualified hospital remains a clinical challenge, and the requirement for facilities and well-screened donors impedes the implementation of FMT. In this review, we aim to provide domestic FMT teams with explicit instructions to facilitate realization and increase the practice of FMT. Based on the Taiwan FMT Expert Consensus and current regulations, we performed a literature review and integrated the experiences of Taiwanese multidisciplinary experts into this article. The content intends to offer clinicians up-to-date evidence and highlight the essential points of FMT.     

大鼠肠道自发荧光微生物的分布

目的 探讨不同发育阶段大鼠肠道自发荧光微生物在肠道内的分布。方法 采用Kinetics IVIS小动物活体成像系统的荧光检测技术对不同发育阶段SD大鼠肠道内自发荧光微生物在肠道内的分布位置进行检测和评估。先对体外培养的大肠杆菌标准菌株进行荧光检测,然后在同一检测条件下分别对大肠杆菌的分布位置进行检测。扩大荧光检测激发光波长范围,去除饲料和粪便等外来自发荧光物质的荧光背景,分别检测出生3、14 d和60 d的SD大鼠肠道内自发荧光微生物的分布。结果 大肠杆菌在485～535 nm激发波长范围内能发荧光。大肠杆菌在出生3 d的SD大鼠肠道系统中主要分布于胃,少量分布于回肠;在出生14 d的SD大鼠肠道系统中主要分布于胃和盲肠,少量分布于回肠;在出生60 d的SD大鼠肠道系统中主要分布于回肠内,少量分布于空肠、结肠和盲肠内。扩大荧光检测激发光波长范围后,自发荧光微生物在出生3 d的SD大鼠肠道系统中主要分布于回肠,其次是胃;在出生14 d的SD大鼠肠道系统中主要分布于胃,其次是盲肠,少量分布于回肠和空肠;在出生60 d的SD大鼠肠道系统中均有分布,主要分布于回肠和盲肠。结论 采用小动物活体成像系统荧光检测技术检测自发荧光肠道微生物,对研究肠道微生物在寄主不同发育阶段肠道内的分布有一定的帮助和指导作用,为肠道微生物与寄主和经胃肠道给药关系的研究提供一定的依据。     

Evaluation of immunogenicity and efficacy of the enterobactin conjugate vaccine in protecting chickens from colibacillosis

Colibacillosis is one of the most common and economically devastating infectious diseases in poultry production worldwide. Innovative universal vaccines are urgently needed to protect chickens from the infections caused by genetically diverse avian pathogenic Escherichia coli (APEC). Enterobactin (Ent) is a highly conserved siderophore required for E. coli iron acquisition and pathogenesis. The Ent-specific antibodies induced by a novel Ent conjugate vaccine significantly inhibited the in vitro growth of diverse APEC strains. In this study, White Leghorn chickens were immunized with the Ent conjugate vaccine using a crossed design with two variables, vaccination (with or without) and APEC challenge (O1, O78, or PBS control), resulting in six study groups (9 to 10 birds/group). The chickens were subcutaneously injected with the vaccine (100 μg per bird) at 7 days of age, followed by booster immunization at 21 days of age. The chickens were intratracheally challenged with an APEC strain (10⁸ CFU/bird) or PBS at 28 days of age. At 5 days post infection, all chickens were euthanized to examine lesions and APEC colonization of the major organs. Immunization of chickens with the Ent vaccine elicited a strong immune response with a 64-fold increase in the level of Ent-specific IgY in serum. The hypervirulent strain O78 caused extensive lesions in lung, air sac, heart, liver, and spleen with significantly reduced lesion scores observed in the vaccinated chickens. Interestingly, the vaccination did not significantly reduce APEC levels in the examined organs. The APEC O1 with low virulence only caused sporadic lesions in the organs in both vaccination and control groups. The Ent conjugate vaccine altered the bacterial community of the ileum and cecum. Taken together, the findings from this study showed the Ent conjugate vaccine could trigger a strong specific immune response and was promising to confer protection against APEC infection.     

肠道微生态失衡与大肠癌发生相关性研究进展

大肠癌是由遗传因素和环境因素共同作用产生并伴随一系列基因突变的消化道恶性肿瘤。由于大肠癌的发病率呈逐年上升趋势,因此对其病因学的研究成为目前的热点。其中,肠道内微生态的失衡致肠癌的作用已经受到研究者的重点关注。本文通过探讨肠道微生态在大肠癌形成过程中的动态变化,研究牛链球菌、梭形杆菌属、脆弱拟杆菌属、大肠埃希菌及幽门螺旋杆菌等多种菌群在大肠癌发展中可能的作用及其机制,为全面理解大肠癌发生发展中微生态的作用、寻找可能的特异性致癌菌群及大肠癌的诊断和治疗提供新的思路。     

无菌小鼠在肠道菌与机体免疫互作机制研究中的应用

肠道菌在机体健康中发挥重要作用,而其中肠道菌发挥作用的具体机制是什么?无菌小鼠作为一种动物模型,在研究肠道菌作用机制的研究中必不可缺。本综述以无菌小鼠模型为基础,探讨肠道菌对机体系统发育、维持中的作用,并重点讨论一些特有的肠道菌在免疫调控中的具体作用。     

Microbiota regulation in constipation and colorectal cancer

The relevance of constipation to the development and progression of colorectal cancer (CRC) is currently a controversial issue. Studies have shown that changes in the composition of the gut microbiota, a condition known as ecological imbalance, are correlated with an increasing number of common human diseases, including CRC and constipation. CRC is the second leading cause of cancer-related deaths worldwide, and constipation has been receiving widespread attention as a risk factor for CRC. Early colonoscopy screening of constipated patients, with regular follow-ups and timely intervention, can help detect early intestinal lesions and reduce the risks of developing colorectal polyps and CRC. As an important regulator of the intestinal microenvironment, the gut microbiota plays a critical role in the onset and progression of CRC. An increasing amount of evidence supports the thought that gut microbial composition and function are key determinants of CRC development and progression, with alterations inducing changes in the expression of host genes, metabolic regulation, and local and systemic immunological responses. Furthermore, constipation greatly affects the composition of the gut microbiota, which in turn influences the susceptibility to intestinal diseases such as CRC. However, the crosstalk between the gut microbiota, constipation, and CRC is still unclear.     

How to: prophylactic interventions for prevention of Clostridioides difficile infection

BackgroundClostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhoea, despite existing guidelines for infection control measures and antimicrobial stewardship. The high associated health and economic burden of CDI calls for novel strategies to prevent the development and spread of CDI in susceptible patients.ObjectivesWe aim to review CDI prophylactic treatment strategies and their implementation in clinical practice.SourcesWe searched PubMed, Embase, Emcare, Web of Science, and the COCHRANE Library databases to identify prophylactic interventions aimed at prevention of CDI. The search was restricted to articles published in English since 2012.ContentA toxin-based vaccine candidate is currently being investigated in a phase III clinical trial. However, a recent attempt to develop a toxin-based vaccine has failed. Conventional probiotics have not yet proved to be an effective strategy for prevention of CDI. New promising microbiota-based interventions that bind and inactivate concomitantly administered antibiotics, such as ribaxamase and DAV-132, have been developed. Prophylaxis of CDI with C. difficile antibiotics should not be performed routinely and should be considered only for secondary prophylaxis in very selected patients who are at the highest imminent risk for recurrent CDI (R-CDI) after a thorough evaluation. Faecal microbiota transplantation (FMT) has proved to be a very effective treatment for patients with multiple recurrences. Bezlotoxumab provides protection against R-CDI, mainly in patients with primary episodes and a high risk of relapse.ImplicationsThere are no proven effective, evidenced-based prophylaxis options for primary CDI. As for secondary prevention, FMT is considered the option of choice in patients with multiple recurrences. Bezlotoxumab can be added to standard treatment for patients at high risk for R-CDI. The most promising strategies are those aimed at reducing changes in intestinal microbiota and development of a new effective non-toxin-based vaccine.