Therapeutic transplantation of the distal gut microbiota

Khoruts, Alexander; Sadowsky, Michael J.

doi:10.1038/mi.2010.79

Cited by 76 publications

(44 citation statements)

References 27 publications

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“…During the last decade, the incidence and severity of diarrhoea associated with Clostridium difficile infection (CDI) has markedly increased (Kelly and LaMont, 2008;Khoruts and Sadowsky, 2011). C. difficile is a Gram-positive, anaerobic, toxinproducing bacterium that typically affects the elderly and hospitalized patients following antibiotic use.…”

Section: Introductionmentioning

confidence: 99%

Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection

et al. 2014

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Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time.Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies.

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Section: Introductionmentioning

confidence: 99%

Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection

et al. 2014

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“…Changes in intestinal mucins, barrier function of TJ and production of the inflammatory cytokines IL-18 and TNF-a were measured during colitis induction. As butyrate enemas and colonic application of faecal bacteria [23] have been shown to be beneficial in clinical studies we also evaluated the therapeutic potential of intrarectal administration of C. tyrobutyricum in the DSS colitis model.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice

Hudcovic

Kolínská

Klepetar

et al. 2012

Clinical and Experimental Immunology

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“…For some patients, antibiotic treatment is effective in resolving diarrhea; however, 20% of individuals will develop recurrent episodes of CDI (5). A limited number of recurrent CDI patients have been treated successfully and cured with fecal transplants, presumably by restoring colonization resistance from the microbiota (6). Vaccines are under clinical development but are currently not available for CDI.…”

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confidence: 99%

Protection from Clostridium difficile Infection in CD4 T Cell- and Polymeric Immunoglobulin Receptor-Deficient Mice

2014

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Clostridium difficile rivals methicillin-resistant Staphylococcus aureus as the primary hospital-acquired infection. C. difficile infection (CDI) caused by toxins A and/or B can manifest as mild diarrhea to life-threatening pseudomembranous colitis. Although most patients recover fully from CDI, ϳ20% undergo recurrent disease. Several studies have demonstrated a correlation between anti-toxin antibody (Ab) and decreased recurrence; however, the contributions of the systemic and mucosal Ab responses remain unclear. Our goal was to use the CDI mouse model to characterize the protective immune response to C. difficile. C57BL/6 mice infected with epidemic C. difficile strain BI17 developed protective immunity against CDI and did not develop CDI upon rechallenge; they generated systemic IgG and IgA as well as mucosal IgA Ab to toxin. To determine if protective immunity to C. difficile could be generated in immunodeficient individuals, we infected CD4 ؊/؊ mice and found that they generated both mucosal and serum IgA anti-toxin Abs and were protected from CDI upon rechallenge, with protection dependent on major histocompatibility complex class II (MHCII) expression; no IgG anti-toxin Ab was found. We found that protection was likely due to neutralizing mucosal IgA Ab. In contrast, pIgR ؊/؊ mice, which lack the receptor to transcytose polymeric Ab across the epithelium, were also protected from CDI, suggesting that although mucosal anti-toxin Ab may contribute to protection, it is not required. We conclude that protection from CDI can occur by several mechanisms and that the mechanism of protection is determined by the state of immunocompetence of the host.

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Therapeutic transplantation of the distal gut microbiota

Cited by 76 publications

References 27 publications

Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection

Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection

Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice

Protection from Clostridium difficile Infection in CD4 T Cell- and Polymeric Immunoglobulin Receptor-Deficient Mice

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