Fecal Microbiota Transplantation for Refractory Clostridium difficile Colitis in Solid Organ Transplant Recipients

Friedman‐Moraco, Rachel; Mehta, Aneesh K.; Lyon, G. Marshall; Kraft, Colleen S.

doi:10.1111/ajt.12577

Cited by 72 publications

(57 citation statements)

References 17 publications

(27 reference statements)

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“…FMT is emerging as an effective treatment option for antibiotic-refractory intestinal infections, such as C. difficile infections, as well as for chronic inflammatory conditions of the gut that are known to be associated with dysbiosis (24,25,40). ABX is often used prior to transplantation, although the overall impact of this strategy on the efficacy of therapy is largely unknown (41).…”

Section: Discussionmentioning

confidence: 99%

“…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). Clinical trials evaluating the benefits of FMT in inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and other gastrointestinal diseases are under way (19,25).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…The patients did not experience infectious complications related to FMT. In the discussion the authors hypothesized that SOT recipients may have more severe alterations in their intestinal microbiota, therefore sequential FMT may be necessary to correct dysbiosis [103].…”

Section: Data From the Literature On Fmt And Immunocompromised Patientsmentioning

confidence: 99%

Fecal microbiota transplantation (FMT) for Clostridium difficile infection: Focus on immunocompromised patients

Bella¹,

Gouliouris²,

Petrosillo³

2015

Journal of Infection and Chemotherapy

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“…Modulation of the microbiome by fecal transplantation has demonstrated some success in the management of refractory Clostridium difficile infection both in immunocompetent and immunocompromised hosts; heightened surveillance for infection after fecal transplantation in immunocompromised hosts is recommended (97,98). Specific microorganisms may contribute to resistance to C. difficile infection (99).…”

Section: Potential Clinical Applications Of Microbiome Management In mentioning

confidence: 99%

The Microbiome, Systemic Immune Function, and Allotransplantation

Nellore

Fishman

2016

Clin Microbiol Rev

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SUMMARYDiverse effects of the microbiome on solid organ transplantation are beginning to be recognized. In allograft recipients, microbial networks are disrupted by immunosuppression, nosocomial and community-based infectious exposures, antimicrobial therapies, surgery, and immune processes. Shifting microbial patterns, including acute infectious exposures, have dynamic and reciprocal interactions with local and systemic immune systems. Both individual microbial species and microbial networks have central roles in the induction and control of innate and adaptive immune responses, in graft rejection, and in ischemia-reperfusion injury. Understanding the diverse interactions between the microbiome and the immune system of allograft recipients may facilitate clinical management in the future.

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Fecal Microbiota Transplantation for Refractory Clostridium difficile Colitis in Solid Organ Transplant Recipients

Cited by 72 publications

References 17 publications

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

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

Fecal microbiota transplantation (FMT) for Clostridium difficile infection: Focus on immunocompromised patients

The Microbiome, Systemic Immune Function, and Allotransplantation

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