The role of the gut microbiome in colonization resistance and recurrent Clostridioides difficile infection.
The role of the gut microbiome in colonization resistance and recurrent Clostridioides difficile infection.
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DOI：
10.1177/17562848221134396
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发表时间：
2022
影响因子：
4.2
通讯作者：
Khanna, Sahil
中科院分区：
文献类型：
--
作者：
Seekatz, Anna Maria;Safdar, Nasia;Khanna, Sahil
关键词：
人类肠道微生物群的物种组成与整体健康有关，健康的肠道微生物群对于维持对病原体的定植抗性至关重要。肠道微生物组组成和功能的破坏降低了定植抗性，并且与几种胃肠道和非胃肠道疾病相关。一个主要的例子是艰难梭菌感染（CDI）和随后的复发性感染，发生后的发展，全身性寄生虫相关的生态失调。用于急性和复发性感染的标准治疗抗生素不能解决生态失调，往往会使病情恶化。此外，单克隆抗体，建议与标准的护理抗生素，用于预防复发的高风险复发患者的复发性CDI，减少复发，但不解决潜在的生态失调。粪便微生物群移植（FMT）是一种不断发展的治疗策略，其中微生物从健康供体粪便中收获并移植到受体的肠道中以恢复肠道微生物群。虽然有效地预防复发性CDI，但一些现有的挑战包括筛查和粪便采集和处理的标准化。美国食品和药物管理局最近发出的安全警报引起了人们对耐多药微生物或严重急性呼吸系统综合征冠状病毒2通过FMT传播的可能性的关注。微生物有益于恢复肠道微生物组的知识增加，导致临床开发了几种比FMT更受监管的新型生物素制剂，这可能有助于改善肠道微生物组的恢复和预防CDI复发。本文综述了肠道微生物组恢复影响对病原体C的定植抗性的机制。很难 肠道微生物组在艰难梭菌感染中的作用 简介：丰富多样的肠道微生物组是免疫系统调节和抵抗病原体定植的关键。肠道微生物组组成的破坏可以使肠道更容易受到疾病的影响，例如由细菌C引起的艰难梭菌感染（CDI）。很难CDI管理呈现出治疗困境，因为它通常用抗生素治疗，这些抗生素可以治疗感染，但也可以破坏微生物组。使用抗生素治疗CDI可以进一步减少微生物多样性并消耗肠道中的有益细菌，导致称为生态失调的状况。抗生素治疗之后可以进行恢复肠道微生物群、增强定植抗性和防止抗生素耐药性发展的治疗。重要的是要评估治疗方案，以确定其安全性和有效性。 方法：研究人员概述了肠道微生物组用于防止病原体在肠道定植的机制。- 抗生素-单克隆抗体-粪便微生物群移植（FMT）他们随后审查了以下治疗CDI的疗效和缺点： 结果：-关键营养素的竞争-抑制性胆汁酸的产生-短链脂肪酸的产生-降低腔内pH值-细菌素的产生肠道共生细菌利用以下机制防止病原体在肠道定植：抗生素治疗被推荐为CDI的标准治疗。 然而，患者在停止治疗后容易复发CDI。单克隆抗体。艰难梭菌毒素可与抗生素一起被推荐沿着以防止CDI复发。然而，这种方法并不能恢复微生物组。FMT是微生物修复的一种方法，其中粪便从健康供体中收集并移植到患者的结肠中。虽然FMT在治疗复发性CDI方面显示出一定的疗效，但该程序并不标准化。人们对通过FMT传播耐多药病原体的可能性提出了安全问题。 结论：能够有效恢复肠道微生物组多样性的治疗方法对于预防CDI复发至关重要。
The species composition of the human gut microbiota is related to overall health, and a healthy gut microbiome is crucial in maintaining colonization resistance against pathogens. Disruption of gut microbiome composition and functionality reduces colonization resistance and has been associated with several gastrointestinal and non-gastrointestinal diseases. One prime example is Clostridioides difficile infection (CDI) and subsequent recurrent infections that occur after the development of systemic antibiotic-related dysbiosis. Standard-of-care antibiotics used for both acute and recurrent infections do not address dysbiosis and often worsen the condition. Moreover, monoclonal antibodies, recommended in conjunction with standard-of-care antibiotics for the prevention of recurrent CDI in patients at high risk of recurrence, reduce recurrences but do not address the underlying dysbiosis. Fecal microbiota transplantation (FMT) is an evolving therapeutic strategy in which microbes are harvested from healthy donor stool and transplanted into the gut of a recipient to restore the gut microbiome. Although effective in the prevention of recurrent CDI, some existing challenges include screening and the standardization of stool acquisition and processing. Recent safety alerts by the US Food and Drug Administration raised concern about the possibility of transmission of multidrug-resistant organisms or severe acute respiratory syndrome coronavirus 2 via FMT. Increased knowledge that microbes are beneficial in restoring the gut microbiome has led to the clinical development of several newer biotherapeutic formulations that are more regulated than FMT, which may allow for improved restoration of the gut microbiome and prevention of CDI recurrence. This review focuses on mechanisms by which gut microbiome restoration could influence colonization resistance against the pathogen C. difficile. The Role of the Gut Microbiome in Clostridioides difficile Infection Introduction: A rich and diverse gut microbiome is key to immune system regulation and colonization resistance against pathogens. A disruption in the gut microbiome composition can make the gut more vulnerable to diseases such as Clostridioides difficile infection (CDI), caused by the bacterium C. difficile. CDI management presents a therapeutic dilemma, as it is usually treated with antibiotics that can treat the infection but also can damage the microbiome. Treatment of CDI using antibiotics can further reduce microbial diversity and deplete beneficial bacteria from the gut leading to a condition called dysbiosis. Antibiotic treatment can be followed by therapies that restore the gut microbiota, boost colonization resistance, and prevent the development of antimicrobial resistance. It is important to evaluate treatment options to determine their safety and effectiveness. Methods: The researchers provided an overview of the mechanisms that the gut microbiome uses to prevent colonization of the gut by pathogens. - Antibiotics - Monoclonal antibodies - Fecal microbiota transplantation (FMT) They subsequently reviewed the efficacy and shortcomings of the following treatments for CDI: Results: - Competition for key nutrients - Production of inhibitory bile acids - Short-chain fatty acid production - Lowering the luminal pH - Production of bacteriocins Commensal intestinal bacteria prevent colonization of the gut by pathogens using mechanisms such as: Antibiotic therapy is recommended as a standard treatment for CDI. However, patients are vulnerable to recurrent CDI after discontinuation of the therapy. Monoclonal antibodies that inactivate C. difficile toxins may be recommended along with antibiotics to prevent recurrent CDI. However, this approach does not restore the microbiome. FMT is one method of microbial restoration, where stool is harvested from a healthy donor and transplanted into a patient’s colon. Although FMT has shown some efficacy in the treatment of recurrent CDI, the procedure is not standardized. Safety concerns have been raised about the possibility of transmission of multidrug-resistant pathogens via FMT. Conclusion: Treatment methods that can efficiently restore the diversity of the gut microbiome are crucial in preventing recurrence of CDI.
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影响因子：
5.2
作者：
Blount K;Jones C;Walsh D;Gonzalez C;Shannon WD
通讯作者：
Shannon WD
影响因子：
6.7
作者：
Caballero S;Carter R;Ke X;Sušac B;Leiner IM;Kim GJ;Miller L;Ling L;Manova K;Pamer EG
通讯作者：
Pamer EG
影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
11.8
作者：
Bartlett, John G.;Gerding, Dale N.
通讯作者：
Gerding, Dale N.
艰难梭菌结肠炎：发病机理和宿主防御。
DOI：
10.1038/nrmicro.2016.108
发表时间：
2016-10
期刊：
Nature reviews. Microbiology
影响因子：
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作者：
通讯作者：
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