Loss of Vancomycin-Resistant Enterococcus Fecal Dominance in an Organ Transplant Patient With Clostridium difficile Colitis After Fecal Microbiota Transplant

Stripling, Joshua; Kumar, Ranjit; Baddley, John W.; Nellore, Anoma; Dixon, Paula; Howard, Donna; Ptacek, Travis; Lefkowitz, Elliot J.; Tallaj, José; Benjamin, William H.; Morrow, Casey D.; Rodríguez, Jorge Martin

doi:10.1093/ofid/ofv078

Cited by 77 publications

(51 citation statements)

References 12 publications

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“…Autologous FMT using cryopreserved microbiota is already being tested in a clinical trial (NCT02269150) at the Memorial Sloan Kettering Cancer Center, USA, with the goal of testing reduction in incidence of CDI and blood-borne infections 103 . Similar issues exist within the solid organ transplant recipient population, and loss of VRE dominance has been documented following FMT performed in treatment of CDI in this setting 104 .…”

Section: Future Applications Of Fmtmentioning

confidence: 74%

Understanding the mechanisms of faecal microbiota transplantation

Khoruts

Sadowsky

2016

Nat Rev Gastroenterol Hepatol

404

330

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This Review summarizes mechanistic investigations in faecal microbiota transplantation (FMT), which has increasingly been adapted into clinical practice as treatment for Clostridium difficile infection (CDI) that cannot be eliminated with antibiotics alone. Administration of healthy donor faecal microbiota in this clinical situation results in its engraftment and restoration of normal gut microbial community structure and functionality. In this Review, we consider several main mechanisms for FMT effectiveness in treatment of CDI, including direct competition of C. difficile with commensal microbiota delivered by FMT, restoration of secondary bile acid metabolism in the colon and repair of the gut barrier by stimulation of the mucosal immune system. Some of these mechanistic insights suggest possibilities for developing novel, next-generation CDI therapeutics. FMT might also have potential applications for non-CDI indications. The gut can become a reservoir of other potential antibiotic-resistant pathogens under pressure of antibiotic treatments, and restoration of normal microbial community structure by FMT might be a promising approach to protect against infections with these pathogens as well. Finally, FMT could be considered for multiple chronic diseases that are associated with some form of dysbiosis. However, considerable research is needed to optimize the FMT protocols for such applications before their therapeutic promise can be evaluated.

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Section: Future Applications Of Fmtmentioning

confidence: 74%

Understanding the mechanisms of faecal microbiota transplantation

Khoruts

Sadowsky

2016

Nat Rev Gastroenterol Hepatol

404

330

View full text Add to dashboard Cite

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“…Whether Barnesiella strains directly mediate VRE clearance or work together with other commensal bacterial species to establish colonization resistance remains to be determined. Although the effectiveness of the microbiota in protecting humans against infection by antibiotic-resistant bacteria is unknown, two recent reports suggest that reestablishment of a diverse microbiota reduces intestinal colonization by VRE and antibiotic-resistant Escherichia coli (19, 20). …”

Section: Microbiota Destruction and Antibiotic-resistant Infectionsmentioning

confidence: 99%

Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

Pamer

2016

Science

348

233

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The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care–associated infections caused by highly antibiotic-resistant bacteria.

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“…FMT has been used to treat bacterial diseases, such as Clostridium difficile and vancomycin-resistant Enterococcus (VRE) infections, which occur when there is dysbiosis (typically after antibiotic use) and these pathogenic bacteria overtake the microbiome and cause diarrheal disease; such infections are typically resistant to treatment (20)(21)(22). Unlike antibiotic therapy, FMT has a rate of efficacy of restoring a diverse microbiota and decreasing GI symptoms of nearly 90% (20,23,24).…”

mentioning

confidence: 99%

Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques

Hensley-McBain

Zevin

Manuzak

et al. 2016

J Virol

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An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT. The greatest microbiota shift was observed after antibiotic treatment. The bacterial community composition at 2 weeks post-FMT resembled the pre-FMT community structure, although differences in the abundances of minor bacterial populations remained. Immunologically, we observed significant increases in the number of peripheral Th17 and Th22 cells and reduced CD4؉ T cell activation in gastrointestinal tissues post-FMT. Importantly, the transplant was well tolerated with no negative clinical side effects. Although this pilot study did not control for the differential contributions of antibiotic treatment and FMT to the observed results, the data suggest that FMT may have beneficial effects that should be further evaluated in larger studies. IMPORTANCE Due to the immunodeficiency and chronic inflammation that occurs during HIV infection, determination of the safety of FMT is crucial to prevent deleterious consequences if it is to be used as a treatment in the future. Here we used the macaque model of HIV infection and performed FMT on six chronically SIV-infected rhesus macaques on antiretroviral treatment. In addition toproviding a preclinical demonstration of the safety of FMT in primates infected with a lentivirus, this study provided a unique opportunity to examine the relationships between alterations to the microbiome and immunological parameters. In this study, we found increased numbers of Th17 and Th22 cells as well as decreased activation of CD4 ؉ T cells post-FMT, and these changes correlated most strongly across all sampling time points with lower-abundance taxonomic groups and other taxonomic groups in the colon. Overall, these data provide evidence that changes in the microbiome, particularly in terms of diversity and changes in minor populations, can enhance immunity and do not have adverse consequences.A ntiretroviral treatment (ART) has substantially decreased the progression to AIDS in human immunodeficiency virus (HIV)-infected individuals. However, despite the ability to suppress viremia, HIV-infected individuals in whom the infection is suppressed by ART have increased rates of morbidity and mortality compared to those of uninfected individuals (1). One mechanism underlying the increased mortality is dysfunction of the gastrointestinal (GI) tract, which is associated with inflammation during HIV infection. Several lines of evidence support the role of GI dysfunction in HIV-related disease, including (i) a consistent association between mortality in HIV-infected individuals and markers of microbial translocation and gut epithe...

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Loss of Vancomycin-Resistant Enterococcus Fecal Dominance in an Organ Transplant Patient With Clostridium difficile Colitis After Fecal Microbiota Transplant

Cited by 77 publications

References 12 publications

Understanding the mechanisms of faecal microbiota transplantation

Understanding the mechanisms of faecal microbiota transplantation

Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques

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