The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Jessica R Allegretti - One of the best experts on this subject based on the ideXlab platform.
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beyond Fecal Microbiota Transplantation developing drugs from the microbiome
The Journal of Infectious Diseases, 2021Co-Authors: Ylaine Gerardin, Jessica R Allegretti, Mark Smith, Sonia Timberlake, Zain KassamAbstract:The transfer of live gut microbes may transform patient care across a range of autoimmune, metabolic, hepatic, and infectious diseases. One early approach, Fecal Microbiota Transplantation, has shown promise in Clostridiodes difficile infection and the potential for improving clinical and public health outcomes for other antibiotic-resistant bacteria. These clinical successes have motivated the development of microbiome drugs, which will need to address challenges in safety, uniformity, and delivery while seeking to preserve the benefits of using whole microbiome communities as novel therapeutics and an innovative platform for drug discovery.
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cost effectiveness analysis of sequential Fecal Microbiota Transplantation for fulminant clostridioides difficile infection
Journal of Gastroenterology and Hepatology, 2021Co-Authors: Zain Kassam, Colleen R Kelly, Sanchit Gupta, Jinyi Zhu, Thomas R Mccarty, Jordan C Pruce, Monika Fischer, Jessica R AllegrettiAbstract:BACKGROUND AND AIM Fulminant Clostridioides difficile infections (FCDI) account for 8% of cases and substantial healthcare burden. Fecal Microbiota Transplantation is recommended for recurrent CDI, but emerging data support use for FCDI. We aimed to assess the cost-effectiveness of a sequential Fecal Microbiota Transplantation (sFMT) protocol for FCDI compared with current standard therapy. METHODS A Markov model simulated patients with FCDI in a 1-year time horizon. The treatment algorithm for up to three sFMTs, clinical probabilities, and direct costs were used from published sources. Outcomes were quality-adjusted life years (QALYs) and costs. The healthcare sector perspective was used with a willingness-to-pay threshold of $100 000 per QALY. RESULTS Sequential Fecal Microbiota Transplantation (FMT) for FCDI was associated with lower overall cost ($28 309 vs $33 980) and higher QALY (0.765 vs 0.686) compared with standard therapy. sFMT is cost-effective in 100% of iterations. sFMT remained cost-effective at cure rates > 44.8% for the first FMT and at stool preparation cost < $6944 per instillation. We find a wide range of efficacies for the first versus second FMT at which sFMT is still preferred. Value of information analysis estimates the expected value of perfect information to be low at $1.89 per person, quantified with net monetary benefit. CONCLUSIONS An sFMT strategy strongly dominates standard therapy, with lower cost and higher QALY. Sensitivity analysis demonstrates benefit even if FMT cure rates are lower than expected and when multiple FMTs are required. FMT material in 2020 was priced at $1695 per treatment but remains cost-effective at a much higher cost.
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Fecal Microbiota Transplantation the evolving risk landscape
The American Journal of Gastroenterology, 2021Co-Authors: Sanchit Gupta, Benjamin H Mullish, Jessica R AllegrettiAbstract:Fecal Microbiota Transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.
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Fecal Microbiota Transplantation in patients with primary sclerosing cholangitis a pilot clinical trial
The American Journal of Gastroenterology, 2019Co-Authors: Jessica R Allegretti, Zain Kassam, Madeline Carrellas, Benjamin H Mullish, Julian R Marchesi, Alexandros Pechlivanis, Mark Smith, Ylaine Gerardin, Sonia TimberlakeAbstract:BACKGROUND:Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut Microbiota has been described in association with PSC, and Fecal Microbiota Transplantation (FMT) has been reported to restore the microbiome in other disease
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Fecal Microbiota Transplantation capsules with targeted colonic versus gastric delivery in recurrent clostridium difficile infection a comparative cohort analysis of high and lose dose
Digestive Diseases and Sciences, 2019Co-Authors: Jessica R Allegretti, Monika Fischer, Sashidhar Sagi, Matthew Bohm, Hala M Fadda, Sejal R Ranmal, Shrish Budree, Abdul Basit, Dean L GlettigAbstract:The original version of the article unfortunately contained an error in article title. The corrected title is 'Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Low Dose'.
Colleen R Kelly - One of the best experts on this subject based on the ideXlab platform.
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cost effectiveness analysis of sequential Fecal Microbiota Transplantation for fulminant clostridioides difficile infection
Journal of Gastroenterology and Hepatology, 2021Co-Authors: Zain Kassam, Colleen R Kelly, Sanchit Gupta, Jinyi Zhu, Thomas R Mccarty, Jordan C Pruce, Monika Fischer, Jessica R AllegrettiAbstract:BACKGROUND AND AIM Fulminant Clostridioides difficile infections (FCDI) account for 8% of cases and substantial healthcare burden. Fecal Microbiota Transplantation is recommended for recurrent CDI, but emerging data support use for FCDI. We aimed to assess the cost-effectiveness of a sequential Fecal Microbiota Transplantation (sFMT) protocol for FCDI compared with current standard therapy. METHODS A Markov model simulated patients with FCDI in a 1-year time horizon. The treatment algorithm for up to three sFMTs, clinical probabilities, and direct costs were used from published sources. Outcomes were quality-adjusted life years (QALYs) and costs. The healthcare sector perspective was used with a willingness-to-pay threshold of $100 000 per QALY. RESULTS Sequential Fecal Microbiota Transplantation (FMT) for FCDI was associated with lower overall cost ($28 309 vs $33 980) and higher QALY (0.765 vs 0.686) compared with standard therapy. sFMT is cost-effective in 100% of iterations. sFMT remained cost-effective at cure rates > 44.8% for the first FMT and at stool preparation cost < $6944 per instillation. We find a wide range of efficacies for the first versus second FMT at which sFMT is still preferred. Value of information analysis estimates the expected value of perfect information to be low at $1.89 per person, quantified with net monetary benefit. CONCLUSIONS An sFMT strategy strongly dominates standard therapy, with lower cost and higher QALY. Sensitivity analysis demonstrates benefit even if FMT cure rates are lower than expected and when multiple FMTs are required. FMT material in 2020 was priced at $1695 per treatment but remains cost-effective at a much higher cost.
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effect of Fecal Microbiota Transplantation on recurrence in multiply recurrent clostridium difficile infection a randomized trial
Annals of Internal Medicine, 2016Co-Authors: Colleen R Kelly, Alexander Khoruts, Christopher Staley, Michael J Sadowsky, Mortadha Abd, Mustafa Alani, Brianna Bakow, Patrizia Curran, Joyce Mckenney, Allison TischAbstract:Evidence for the efficacy and safety of Fecal Microbiota Transplantation (FMT) in recurrent Clostridium difficile infection (CDI) is limited. In this randomized trial conducted at 2 academic medica...
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predictors of early failure after Fecal Microbiota Transplantation for the therapy of clostridium difficile infection a multicenter study
The American Journal of Gastroenterology, 2016Co-Authors: Monika Fischer, Dina Kao, Shama R Mehta, Tracey Martin, Joseph Dimitry, Ammar Hassanzadeh Keshteli, Gwendolyn Cook, Emmalee Phelps, Brian Sipe, Colleen R KellyAbstract:Predictors of Early Failure After Fecal Microbiota Transplantation for the Therapy of Clostridium Difficile Infection: A Multicenter Study
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update on Fecal Microbiota Transplantation 2015 indications methodologies mechanisms and outlook
Gastroenterology, 2015Co-Authors: Colleen R Kelly, David T Rubin, Stacy A Kahn, Purna C Kashyap, Loren Laine, Ashish Atreja, Thomas C MooreAbstract:The community of microorganisms within the human gut (or Microbiota) is critical to health and functions with a level of complexity comparable to that of an organ system. Alterations of this ecology (or dysbiosis) have been implicated in a number of disease states, and the prototypical example is Clostridium difficile infection (CDI). Fecal Microbiota Transplantation (FMT) has been demonstrated to durably alter the gut Microbiota of the recipient and has shown efficacy in the treatment of patients with recurrent CDI. There is hope that FMT may eventually prove beneficial for the treatment of other diseases associated with alterations in gut Microbiota, such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome, to name a few. Although the basic principles that underlie the mechanisms by which FMT shows therapeutic efficacy in CDI are becoming apparent, further research is needed to understand the possible role of FMT in these other conditions. Although relatively simple to perform, questions regarding both short-term and long-term safety as well as the complex and rapidly evolving regulatory landscape has limited widespread use. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current "whole-stool" transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future.
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weight gain after Fecal Microbiota Transplantation
Open Forum Infectious Diseases, 2015Co-Authors: Neha Alang, Colleen R KellyAbstract:Fecal Microbiota Transplantation (FMT) is a promising treatment for recurrent Clostridium difficile infection. We report a case of a woman successfully treated with FMT who developed new-onset obesity after receiving stool from a healthy but overweight donor. This case may stimulate further studies on the mechanisms of the nutritional-neural-Microbiota axis and reports of outcomes in patients who have used nonideal donors for FMT.
Zain Kassam - One of the best experts on this subject based on the ideXlab platform.
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dynamic colonization of microbes and their functions after Fecal Microbiota Transplantation for inflammatory bowel disease
Mbio, 2021Co-Authors: Zain Kassam, Mark Smith, Nathaniel D Chu, Jessica W Crothers, Le Tt Nguyen, Sean M Kearney, Cheryl CollinsAbstract:For Fecal Microbiota Transplantation (FMT) to be successful in immune diseases like inflammatory bowel disease, it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize a recipient patient and persist in sufficient quantity and for a sufficient period of time to produce a clinical benefit. Few studies, however, have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial functions and interactions with the host immune system. Using 16S, metagenomic, and immunoglobulin A (IgA) sequencing, we analyzed hundreds of longitudinal microbiome samples from a randomized controlled trial of 12 patients with ulcerative colitis who received Fecal transplant or placebo for 12 weeks. We uncovered diverse competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced a dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening symptoms. We evaluated the transfer of microbial functions, including desired ones, such as butyrate production, and unintended ones, such as antibiotic resistance. By profiling bacteria coated with IgA, we identified bacteria associated with inflammation and found that microbial interactions with the host immune system can be transferred across people, which could play a role in gut microbiome therapeutics for immune-related diseases. Our findings shed light on the colonization dynamics of gut microbes and their functions in the context of FMT to treat a complex disease-information that may provide a foundation for developing more-targeted therapeutics. IMPORTANCE Fecal Microbiota Transplantation (FMT)-transferring Fecal microbes from a healthy donor to a sick patient-has shown promise for gut diseases such as inflammatory bowel disease. Unlike pharmaceuticals, however, Fecal transplants are complex mixtures of living organisms, which must then interact with the microbes and immune system of the recipient. We sought to understand these interactions by tracking the microbes of 12 inflammatory bowel disease patients who received Fecal transplants for 12 weeks. We uncovered a range of dynamics. For example, one patient experienced successful transfer of donor bacteria, only to lose them after 10 weeks. We similarly evaluated transfer of microbial functions, including how they interacted with the recipient's immune system. Our findings shed light on the colonization dynamics of gut microbes, as well as their functions in the context of FMT-information that may provide a critical foundation for the development of more-targeted therapeutics.
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beyond Fecal Microbiota Transplantation developing drugs from the microbiome
The Journal of Infectious Diseases, 2021Co-Authors: Ylaine Gerardin, Jessica R Allegretti, Mark Smith, Sonia Timberlake, Zain KassamAbstract:The transfer of live gut microbes may transform patient care across a range of autoimmune, metabolic, hepatic, and infectious diseases. One early approach, Fecal Microbiota Transplantation, has shown promise in Clostridiodes difficile infection and the potential for improving clinical and public health outcomes for other antibiotic-resistant bacteria. These clinical successes have motivated the development of microbiome drugs, which will need to address challenges in safety, uniformity, and delivery while seeking to preserve the benefits of using whole microbiome communities as novel therapeutics and an innovative platform for drug discovery.
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cost effectiveness analysis of sequential Fecal Microbiota Transplantation for fulminant clostridioides difficile infection
Journal of Gastroenterology and Hepatology, 2021Co-Authors: Zain Kassam, Colleen R Kelly, Sanchit Gupta, Jinyi Zhu, Thomas R Mccarty, Jordan C Pruce, Monika Fischer, Jessica R AllegrettiAbstract:BACKGROUND AND AIM Fulminant Clostridioides difficile infections (FCDI) account for 8% of cases and substantial healthcare burden. Fecal Microbiota Transplantation is recommended for recurrent CDI, but emerging data support use for FCDI. We aimed to assess the cost-effectiveness of a sequential Fecal Microbiota Transplantation (sFMT) protocol for FCDI compared with current standard therapy. METHODS A Markov model simulated patients with FCDI in a 1-year time horizon. The treatment algorithm for up to three sFMTs, clinical probabilities, and direct costs were used from published sources. Outcomes were quality-adjusted life years (QALYs) and costs. The healthcare sector perspective was used with a willingness-to-pay threshold of $100 000 per QALY. RESULTS Sequential Fecal Microbiota Transplantation (FMT) for FCDI was associated with lower overall cost ($28 309 vs $33 980) and higher QALY (0.765 vs 0.686) compared with standard therapy. sFMT is cost-effective in 100% of iterations. sFMT remained cost-effective at cure rates > 44.8% for the first FMT and at stool preparation cost < $6944 per instillation. We find a wide range of efficacies for the first versus second FMT at which sFMT is still preferred. Value of information analysis estimates the expected value of perfect information to be low at $1.89 per person, quantified with net monetary benefit. CONCLUSIONS An sFMT strategy strongly dominates standard therapy, with lower cost and higher QALY. Sensitivity analysis demonstrates benefit even if FMT cure rates are lower than expected and when multiple FMTs are required. FMT material in 2020 was priced at $1695 per treatment but remains cost-effective at a much higher cost.
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Fecal Microbiota Transplantation in patients with primary sclerosing cholangitis a pilot clinical trial
The American Journal of Gastroenterology, 2019Co-Authors: Jessica R Allegretti, Zain Kassam, Madeline Carrellas, Benjamin H Mullish, Julian R Marchesi, Alexandros Pechlivanis, Mark Smith, Ylaine Gerardin, Sonia TimberlakeAbstract:BACKGROUND:Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut Microbiota has been described in association with PSC, and Fecal Microbiota Transplantation (FMT) has been reported to restore the microbiome in other disease
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scaling safe access to Fecal Microbiota Transplantation past present and future
Current Gastroenterology Reports, 2018Co-Authors: Pratik Panchal, Shrish Budree, Alex Scheeler, Geraldine Medina, Monica Seng, Wing Fei Wong, Ryan J Elliott, Ryan Eliott, Thomas Mitchell, Zain KassamAbstract:Universal stool banks (USBs) have emerged as a potential model for scaling access to Fecal Microbiota Transplantation (FMT) for Clostridium difficile infection (CDI). In this review, we outline the historical barriers constraining access to FMT, the evidence on methods and outcomes of USBs, and potential future directions for expanding access. Key historical barriers to FMT access include regulatory uncertainty, operational complexity of sourcing screened donor material, and logistical challenges of delivering fresh treatment preparations. USBs have demonstrated that FMT can be delivered safely at scale by centralizing donor selection, material processing, and safety monitoring. More evidence is needed to optimize USB methods, including for donor screening, material processing, and novel delivery modalities. USBs have catalyzed broad access to FMT in North America and Europe. Future directions include developing evidence regarding oral preparations, harmonizing guidelines, disseminating best practice protocols, establishing long-term safety profiles, and expanding access to geographic areas of unmet need
Monika Fischer - One of the best experts on this subject based on the ideXlab platform.
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cost effectiveness analysis of sequential Fecal Microbiota Transplantation for fulminant clostridioides difficile infection
Journal of Gastroenterology and Hepatology, 2021Co-Authors: Zain Kassam, Colleen R Kelly, Sanchit Gupta, Jinyi Zhu, Thomas R Mccarty, Jordan C Pruce, Monika Fischer, Jessica R AllegrettiAbstract:BACKGROUND AND AIM Fulminant Clostridioides difficile infections (FCDI) account for 8% of cases and substantial healthcare burden. Fecal Microbiota Transplantation is recommended for recurrent CDI, but emerging data support use for FCDI. We aimed to assess the cost-effectiveness of a sequential Fecal Microbiota Transplantation (sFMT) protocol for FCDI compared with current standard therapy. METHODS A Markov model simulated patients with FCDI in a 1-year time horizon. The treatment algorithm for up to three sFMTs, clinical probabilities, and direct costs were used from published sources. Outcomes were quality-adjusted life years (QALYs) and costs. The healthcare sector perspective was used with a willingness-to-pay threshold of $100 000 per QALY. RESULTS Sequential Fecal Microbiota Transplantation (FMT) for FCDI was associated with lower overall cost ($28 309 vs $33 980) and higher QALY (0.765 vs 0.686) compared with standard therapy. sFMT is cost-effective in 100% of iterations. sFMT remained cost-effective at cure rates > 44.8% for the first FMT and at stool preparation cost < $6944 per instillation. We find a wide range of efficacies for the first versus second FMT at which sFMT is still preferred. Value of information analysis estimates the expected value of perfect information to be low at $1.89 per person, quantified with net monetary benefit. CONCLUSIONS An sFMT strategy strongly dominates standard therapy, with lower cost and higher QALY. Sensitivity analysis demonstrates benefit even if FMT cure rates are lower than expected and when multiple FMTs are required. FMT material in 2020 was priced at $1695 per treatment but remains cost-effective at a much higher cost.
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Fecal Microbiota Transplantation redefining surgical management of refractory clostridium difficile infection
Clinics in Colon and Rectal Surgery, 2020Co-Authors: Yao Wen Cheng, Monika FischerAbstract:Fecal Microbiota Transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a diseased individual for therapeutic purposes. It has a clearly defined role in the treatment of recurrent Clostridium difficile (reclassified as " Clostridioides difficile ") infection (CDI), with cure rates over 90% and decreased rates of subsequent recurrence compared with anti-CDI antibiotics. There is emerging evidence that FMT is also effective in the treatment of severe and fulminant CDI, with associated decreases in mortality and colectomy rates compared with standard antibiotic therapy. FMT shows promise as salvage therapy for critically-ill CDI patients refractory to maximum medical therapy and not deemed to be surgical candidates. FMT should be considered early in the course of severe CDI and should be delivered immediately in patients with signs of refractory CDI. Expansion of FMT's use along the spectrum of CDI severity has potential to decrease associated rates of mortality and colectomy.
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Fecal Microbiota Transplantation capsules with targeted colonic versus gastric delivery in recurrent clostridium difficile infection a comparative cohort analysis of high and lose dose
Digestive Diseases and Sciences, 2019Co-Authors: Jessica R Allegretti, Monika Fischer, Sashidhar Sagi, Matthew Bohm, Hala M Fadda, Sejal R Ranmal, Shrish Budree, Abdul Basit, Dean L GlettigAbstract:The original version of the article unfortunately contained an error in article title. The corrected title is 'Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Low Dose'.
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the current landscape and lessons from Fecal Microbiota Transplantation for inflammatory bowel disease past present and future
Inflammatory Bowel Diseases, 2017Co-Authors: Jessica R Allegretti, Monika Fischer, Lindsay Eysenbach, Najwa Elnachef, Colleen Kelly, Zain KassamAbstract:Fecal Microbiota Transplantation (FMT) has changed the standard of care for Clostridium difficile infection. However, there is limited data focusing on efficacy and safety profile of FMT in patients with C. difficile infection with underlying inflammatory bowel disease (IBD), including the risk of IBD flare. Recently, there is also emerging evidence supporting the role of FMT to treat IBD including promising randomized trials in ulcerative colitis. However, with heterogeneity across these studies, the clinical application of this emerging therapy has yet to be fully elucidated. Here, we aim to review the current landscape of this rapidly developing field, mapping the efficacy and safety of FMT (1) to treat C. difficile infection in patients with IBD, (2) to treat underlying IBD, and (3) outline ongoing clinical trials and the future of the microbiome space.
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the risk of inflammatory bowel disease flares after Fecal Microbiota Transplantation systematic review and meta analysis
Gut microbes, 2017Co-Authors: Taha Qazi, Zain Kassam, Monika Fischer, Thelina Amaratunga, Edward L Barnes, Jessica R AllegrettiAbstract:ABSTRACTSeveral studies have suggested worsening in inflammatory bowel disease (IBD) activity following Fecal Microbiota Transplantation (FMT). We aimed to assess the risk of worsening in IBD activity following FMT. An electronic search was conducted using MEDLINE (1946-June 2016), EMBASE (1954-June 2016) and Cochrane Central Register of Controlled Trials (2016). Studies in which FMT was provided to IBD patients for IBD management or (Clostridium difficile infection) CDI treatment were included. The primary outcome was the rate of worsening in IBD activity. Results: Twenty-nine studies with 514 FMT-treated IBD patients were included. Range of follow up was 4 weeks to 3 y. The pooled rate of IBD worsening was 14.9% (95% CI 10–21%). Heterogeneity was detected: I2 D 52.1%, Cochran Q test D 58.1, p D 0.01. A priori subgroup analyses were performed. Although not significant, the pooled rate of worsening in IBD activity following FMT for CDI (22.7% (95% CI: 13–36%)) was higher compared with FMT for IBD (11.1% (...
Alexander Khoruts - One of the best experts on this subject based on the ideXlab platform.
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treatment of recurrent clostridium difficile infection using Fecal Microbiota Transplantation in patients with inflammatory bowel disease
Gut microbes, 2017Co-Authors: Krista M Newman, Byron P Vaughn, Kevin Rank, Alexander KhorutsAbstract:We recently compared results of Fecal Microbiota Transplantation (FMT) in patients with refractory, recurrent Clostridium difficile infection (rCDI), with and without underlying inflammatory bowel disease (IBD). Here we extend this cohort and analyze outcomes in greater detail by subtype of IBD. We find that FMT is generally effective in breaking the cycle of CDI recurrence, but its effects on overall IBD progression are much less predictable. We discuss several challenges intrinsic to this complex clinical situation and outline the next steps that can address these challenges going forward.
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effect of Fecal Microbiota Transplantation on recurrence in multiply recurrent clostridium difficile infection a randomized trial
Annals of Internal Medicine, 2016Co-Authors: Colleen R Kelly, Alexander Khoruts, Christopher Staley, Michael J Sadowsky, Mortadha Abd, Mustafa Alani, Brianna Bakow, Patrizia Curran, Joyce Mckenney, Allison TischAbstract:Evidence for the efficacy and safety of Fecal Microbiota Transplantation (FMT) in recurrent Clostridium difficile infection (CDI) is limited. In this randomized trial conducted at 2 academic medica...
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species and genus level resolution analysis of gut Microbiota in clostridium difficile patients following Fecal Microbiota Transplantation
Microbiome, 2014Co-Authors: Vijay Shankar, Alexander Khoruts, Matthew J Hamilton, Amanda Kilburn, Tatsuya Unno, Oleg Paliy, Michael J SadowskyAbstract:Background: Clostridium difficile is an opportunistic human intestinal pathogen, and C. difficile infection (CDI) is one of the main causes of antibiotic-induced diarrhea and colitis. One successful approach to combat CDI, particularly recurrent form of CDI, is through Transplantation of Fecal Microbiota from a healthy donor to the infected patient. In this study we investigated the distal gut microbial communities of three CDI patients before and after Fecal Microbiota Transplantation, and we compared these communities to the composition of the donor’s Fecal Microbiota. We utilized phylogenetic Microbiota Array, high-throughput Illumina sequencing, and fluorescent in situ hybridization to profile Microbiota composition down to the genus and species level resolution. Results: The original patients’ Microbiota had low diversity, was dominated by members of Gammaproteobacteria and Bacilli, and had low numbers of Clostridia and Bacteroidia. At the genus level, Fecal samples of CDI patients were rich in members of the Lactobacillus, Streptococcus ,a ndEnterobacter genera. In comparison, the donor community was dominated by Clostridia and had significantly higher diversity and evenness. The patients’ distal gut communities were completely transformed within 3 days following Fecal Transplantation, and these communities remained stable in each patient for at least 4 months. Despite compositional differences among recipients’ pre-treatment gut Microbiota, the transplanted gut communities were highly similar among recipients post-Transplantation, were indistinguishable from that of the donor, and were rich in members of Blautia, Coprococcus ,a ndFaecalibacterium .I n each case, the gut Microbiota restoration led to a complete patient recovery and symptom alleviation. Conclusion: We conclude that C. difficile infection can be successfully treated by Fecal Microbiota Transplantation and that this leads to stable transformation of the distal gut microbial community from the one abundant in aerotolerant species to that dominated by members of the Clostridia.
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species and genus level resolution analysis of gut Microbiota in clostridium difficile patients following Fecal Microbiota Transplantation
Microbiome, 2014Co-Authors: Vijay Shankar, Alexander Khoruts, Matthew J Hamilton, Amanda Kilburn, Tatsuya Unno, Oleg Paliy, Michael J SadowskyAbstract:Clostridium difficile is an opportunistic human intestinal pathogen, and C. difficile infection (CDI) is one of the main causes of antibiotic-induced diarrhea and colitis. One successful approach to combat CDI, particularly recurrent form of CDI, is through Transplantation of Fecal Microbiota from a healthy donor to the infected patient. In this study we investigated the distal gut microbial communities of three CDI patients before and after Fecal Microbiota Transplantation, and we compared these communities to the composition of the donor’s Fecal Microbiota. We utilized phylogenetic Microbiota Array, high-throughput Illumina sequencing, and fluorescent in situ hybridization to profile Microbiota composition down to the genus and species level resolution. The original patients’ Microbiota had low diversity, was dominated by members of Gammaproteobacteria and Bacilli, and had low numbers of Clostridia and Bacteroidia. At the genus level, Fecal samples of CDI patients were rich in members of the Lactobacillus, Streptococcus, and Enterobacter genera. In comparison, the donor community was dominated by Clostridia and had significantly higher diversity and evenness. The patients’ distal gut communities were completely transformed within 3 days following Fecal Transplantation, and these communities remained stable in each patient for at least 4 months. Despite compositional differences among recipients’ pre-treatment gut Microbiota, the transplanted gut communities were highly similar among recipients post-Transplantation, were indistinguishable from that of the donor, and were rich in members of Blautia, Coprococcus, and Faecalibacterium. In each case, the gut Microbiota restoration led to a complete patient recovery and symptom alleviation. We conclude that C. difficile infection can be successfully treated by Fecal Microbiota Transplantation and that this leads to stable transformation of the distal gut microbial community from the one abundant in aerotolerant species to that dominated by members of the Clostridia.
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Fecal Microbiota Transplantation and emerging applications
Nature Reviews Gastroenterology & Hepatology, 2012Co-Authors: Thomas J Borody, Alexander KhorutsAbstract:Fecal Microbiota Transplantation (FMT) has been utilized sporadically for over 50 years. In the past few years, Clostridium difficile infection (CDI) epidemics in the USA and Europe have resulted in the increased use of FMT, given its high efficacy in eradicating CDI and associated symptoms. As more patients request treatment and more clinics incorporate FMT into their treatment repertoire, reports of applications outside of CDI are emerging, paving the way for the use of FMT in several idiopathic conditions. Interest in this therapy has largely been driven by new research into the gut Microbiota, which is now beginning to be appreciated as a microbial human organ with important roles in immunity and energy metabolism. This new paradigm raises the possibility that many diseases result, at least partially, from Microbiota-related dysfunction. This understanding invites the investigation of FMT for several disorders, including IBD, IBS, the metabolic syndrome, neurodevelopmental disorders, autoimmune diseases and allergic diseases, among others. The field of Microbiota-related disorders is currently in its infancy; it certainly is an exciting time in the burgeoning science of FMT and we expect to see new and previously unexpected applications in the near future. Well-designed and well-executed randomized trials are now needed to further define these Microbiota-related conditions.
