MILESTONES

MILESTONE 2 community structure in the colon. Currently, a research consortium is recruiting patients to a clinical Faecal transplantation trial examining whether FMT is safe, and can prevent recurrent C. difficile-associated disease. FMT for Clostridioides difficile infection could inhibit C. difficile by multiple mechanisms, such as suppression by antimicrobial peptides, inhibition of spore germination and vegetative growth, competition for nutrients, and activation of colonization resistance (MILESTONE 13). To reduce costs and increase patient and clinician convenience, oral delivery of faecal microbiota has been tested. In 2017, a randomized clinical trial showed that FMT deliv- ery by oral capsule was non-inferior to delivery via , suggest- ing oral capsules could be an effective treatment approach for recurrent C. difficile infection. FMT has also been investigated

Credit: Science Photo Library / Alamy Stock Photo Stock Alamy / Library Photo Science Credit: for non-C. difficile indications, such as ulcerative and drug-induced In 1958, Eiseman et al. reported the and colleagues also noted this link colitis, and has shown some promise. successful treatment of pseudomem- to prior broad-spectrum FMT from lean donors has also been branous enterocolitis using a faecal treatment in their patients and spec- shown to increase insulin sensitivity . Since then, faecal microbiota ulated that disruption of the ‘healthy in men with metabolic syndrome. transplantation (FMT) has become gut flora’ underlies infection. Thus, since the pioneering report widely accepted as a successful rescue The intention of performing FMT from Eiseman and colleagues, FMT treatment for recurrent Clostridioides is restoration of the normal function has become an effective therapy for difficile infection. FMT is also being of the . In Eiseman recurrent C. difficile infection and investigated for other indications. and colleagues’ report, culture shows promise for treating other Eiseman and colleagues presented of stool samples obtained during diseases. the cases of four patients with infection showed the presence of Louise Stone, Nature Reviews Urology pseudomembranous enterocolitis. Staphylococcus aureus, which, at the They used with faeces from time, was considered to be a pos- ORIGINAL ARTICLE Eiseman B. et al. Fecal enema as an adjunct in the treatment of healthy donors after other therapy sible cause of pseudomembranous pseudomembranous enterocolitis. Surgery 44, options failed. The patients had a enterocolitis. S. aureus disappeared 854–859 (1958). FURTHER READING Khoruts A. & Sadowsky M. J. rapid recovery from their symptoms. from the stool sample cultures Understanding the mechanisms of faecal FMT is now C. difficile infection can cause after administration of a faecal microbiota transplantation. Nat. Rev. Gastro. Hep. debilitating diarrhoeal symptoms enema in association with clinical 13, 508–516 (2016) | Pamer, E. G. Fecal microbiota an effective transplantation: effectiveness, complexities, and treatment when the bacterial spores germinate improvement. The authors suggested lingering concerns. Mucosal Immunol. 7, 210–2014 into vegetative cells that produce that normal colonic non-patho- (2014) | Schwan A. et al. Relapsing Clostridium option for enterotoxins, resulting in colonic gens displaced the colitis-causing difficile enterocolitis cured by rectal infusion of homologous faeces. Lancet 322, 845 (1983) | recurrent and the formation , which, decades later, was Gorbach S. L., Chang T. W. & Goldin B. Successful C. difficile of ‘pseudomembranes’ consisting demonstrated to be C. difficile. treatment of relapsing Clostridium difficile colitis of inflammatory cells, dead cells Since Eiseman and co-workers’ with GG. Lancet 330, 1519 (1987) | infection and Tvede M, Rask-Madsen J. Bacteriotherapy for and debris. Over the past couple of publication, others have reported Clostridium difficile diarrhoea. Lancet 1, 1156– is believed decades, C. difficile infection has success using faecal enemas, 1160 (1989) | US National Library of Medicine. Microbial Restoration for Individuals With One or to normalize increased in incidence, morbidity Lactobacillus rhamnosus GG (a pro- More Recurrences of Clostridium Difficile the microbial and mortality, and has become biotic) and bacteriotherapy (using a Associated Disease (CDAD) https://ClinicalTrials. known as a ‘superbug’. Despite anti- mixture of facultatively aerobic and gov/show/NCT03548051 (2018) | Kao, D. et al. diversity and Effect of oral capsule- vs. colonoscopy-delivered biotics being the standard treatment anaerobic ) to treat relapsing fecal microbiota transplantation on recurrent community for C. difficile infection, they also C. difficile enterocolitis. Clostridium difficile infection: a randomized clinical trial. JAMA 318, 1985–1993 (2017) | Vrieze, A. structure in often are the cause of infection owing FMT is now an effective treat- et al. Transfer of intestinal microbiota from lean the colon to their suppressive effects on native ment option for recurrent C. difficile donors increases insulin sensitivity in individuals gut microbiota and subsequent infection and is believed to nor- with metabolic syndrome. Gastroenterology 143, 913–916 (2012). overgrowth of C. difficile. Eiseman malize the microbial diversity and

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