Changes in microbial ecology after fecal microbiota transplantation for recurrent C. difficile infection affected by underlying inflammatory bowel disease

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Abstract

Background

Gut microbiota play a key role in maintaining homeostasis in the human gut. Alterations in the gut microbial ecosystem predispose to Clostridium difficile infection (CDI) and gut inflammatory disorders such as inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor can restore gut microbial diversity and pathogen colonization resistance; consequently, it is now being investigated for its ability to improve inflammatory gut conditions such as IBD. In this study, we investigated changes in gut microbiota following FMT in 38 patients with CDI with or without underlying IBD.

Results

There was a significant change in gut microbial composition towards the donor microbiota and an overall increase in microbial diversity consistent with previous studies after FMT. FMT was successful in treating CDI using a diverse set of donors, and varying degrees of donor stool engraftment suggesting that donor type and degree of engraftment are not drivers of a successful FMT treatment of CDI. However, patients with underlying IBD experienced an increased number of CDI relapses (during a 24-month follow-up) and a decreased growth of new taxa, as compared to the subjects without IBD. Moreover, the need for IBD therapy did not change following FMT. These results underscore the importance of the existing gut microbial landscape as a decisive factor to successfully treat CDI and potentially for improvement of the underlying pathophysiology in IBD.

Conclusions

FMT leads to a significant change in microbial diversity in patients with recurrent CDI and complete resolution of symptoms. Stool donor type (related or unrelated) and degree of engraftment are not the key for successful treatment of CDI by FMT. However, CDI patients with IBD have higher proportion of the original community after FMT and lack of improvement of their IBD symptoms and increased episodes of CDI on long-term follow-up.

Electronic supplementary material

The online version of this article (doi:10.1186/s40168-017-0269-3) contains supplementary material, which is available to authorized users.

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Most cited references 12

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Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial.

Paul Moayyedi, Michael Surette, Peter Kim … (2015)

Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial.

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EMPeror: a tool for visualizing high-throughput microbial community data

Yoshiki Vázquez-Baeza, Meg Pirrung, Antonio González González … (2013)

Background As microbial ecologists take advantage of high-throughput sequencing technologies to describe microbial communities across ever-increasing numbers of samples, new analysis tools are required to relate the distribution of microbes among larger numbers of communities, and to use increasingly rich and standards-compliant metadata to understand the biological factors driving these relationships. In particular, the Earth Microbiome Project drives these needs by profiling the genomic content of tens of thousands of samples across multiple environment types. Findings Features of EMPeror include: ability to visualize gradients and categorical data, visualize different principal coordinates axes, present the data in the form of parallel coordinates, show taxa as well as environmental samples, dynamically adjust the size and transparency of the spheres representing the communities on a per-category basis, dynamically scale the axes according to the fraction of variance each explains, show, hide or recolor points according to arbitrary metadata including that compliant with the MIxS family of standards developed by the Genomic Standards Consortium, display jackknifed-resampled data to assess statistical confidence in clustering, perform coordinate comparisons (useful for procrustes analysis plots), and greatly reduce loading times and overall memory footprint compared with existing approaches. Additionally, ease of sharing, given EMPeror’s small output file size, enables agile collaboration by allowing users to embed these visualizations via emails or web pages without the need for extra plugins. Conclusions Here we present EMPeror, an open source and web browser enabled tool with a versatile command line interface that allows researchers to perform rapid exploratory investigations of 3D visualizations of microbial community data, such as the widely used principal coordinates plots. EMPeror includes a rich set of controllers to modify features as a function of the metadata. By being specifically tailored to the requirements of microbial ecologists, EMPeror thus increases the speed with which insight can be gained from large microbiome datasets.

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Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.

Sudarshan Paramsothy, Michael Kamm, Nadeem Kaakoush … (2017)

The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis.

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Author and article information

Contributors

Darrell S. Pardi: pardi.darrell@mayo.edu

Purna C. Kashyap: kashyap.purna@mayo.edu

Journal

Journal ID (nlm-ta): Microbiome

Journal ID (iso-abbrev): Microbiome

Title: Microbiome

Publisher: BioMed Central (London )

ISSN (Electronic): 2049-2618

Publication date (Electronic): 15 May 2017

Publication date PMC-release: 15 May 2017

Publication date Collection: 2017

Volume: 5

Electronic Location Identifier: 55

Affiliations

[1 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Division of Gastroenterology and Hepatology, , Mayo Clinic, ; Rochester, MN 55905 USA

[2 ]Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA USA

[3 ]Department of Pediatrics, University of California, San Diego, La Jolla, CA USA

[4 ]ISNI 0000000096214564, GRID grid.266190.a, Department of Chemical and Biological Engineering, , University of Colorado, ; Boulder, CO USA

[5 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Division of Colorectal Surgery, , Mayo Clinic, ; Rochester, MN USA

[6 ]ISNI 0000000419368657, GRID grid.17635.36, BioTechnology Institute, , University of Minnesota, ; Minneapolis, MN USA

[7 ]ISNI 0000000419368657, GRID grid.17635.36, Division of Gastroenterology, , University of Minnesota, ; Minneapolis, MN USA

Article

Publisher ID: 269

DOI: 10.1186/s40168-017-0269-3

PMC ID: 5433077

PubMed ID: 28506317

SO-VID: 60d872a8-647e-4603-ab3c-371ca1b5ff54

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 7 November 2016

Date accepted : 23 April 2017

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;

Award ID: NIH K08 DK100638

Award Recipient : Purna C. Kashyap

Funded by: Global Probiotic Council

Funded by: Minnesota Partnership for Biotechnology and Genomics

Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/100006108, National Center for Advancing Translational Sciences;

Award ID: UL1 TR000135

Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;

Award ID: P30DK084567

Funded by: Center for Individualized Medicine

Custom metadata

Keywords: fecal microbiota transplantation,microbiome,clostridium difficile infection,inflammatory bowel disease

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Keywords: fecal microbiota transplantation, microbiome, clostridium difficile infection, inflammatory bowel disease

Changes in microbial ecology after fecal microbiota transplantation for recurrent C. difficile infection affected by underlying inflammatory bowel disease

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Tick microbiome

Most cited references 12

Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial.

EMPeror: a tool for visualizing high-throughput microbial community data

Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.

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