Microbiome predictors of dysbiosis and VRE decolonization in patients with recurrent <em>C. difficile</em> infections in a multi-center retrospective study

Marina Santiago; Lindsay Eysenbach; Jessica Allegretti; Olga Aroniadis; Lawrence J. Brandt; Monika Fischer; Ari Grinspan; Colleen Kelly; Casey Morrow; Martin Rodriguez; Majdi Osman; Zain Kassam; Mark B. Smith; Sonia Timberlake; Marina Santiago; Lindsay Eysenbach; Jessica Allegretti; Olga Aroniadis; Lawrence J. Brandt; Monika Fischer; Ari Grinspan; Colleen Kelly; Casey Morrow; Martin Rodriguez; Majdi Osman; Zain Kassam; Mark B. Smith; Sonia Timberlake

doi:10.3934/microbiol.2019.1.1

AIMS Microbiology

2019, Volume 5, Issue 1: 1-18. doi: 10.3934/microbiol.2019.1.1

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Microbiome predictors of dysbiosis and VRE decolonization in patients with recurrent C. difficile infections in a multi-center retrospective study

1.
Finch Therapeutics, 200 Inner Belt Rd, Somerville, MA 02143, USA
2.
OpenBiome, 2067 Massachusetts Ave, Cambridge, MA 02140, USA
3.
Division of Gastroenterology, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115, USA
4.
Department of Medicine (Gastroenterology), Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA
5.
Division of Gastroenterology, Indiana University School of Medicine, 340 W. 10th St, Indianapolis, IN 46202, USA
6.
Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA
7.
Women’s Medicine Collaborative, Brown Alpert Medial School, 222 Richmond St, Providence, RI 02903, USA
8.
Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, 1720 2nd Ave S, Birmingham, AL 35294, USA
9.
Division of Infectious Diseases, University of Alabama at Birmingham School of Medicine, 1670 University Blvd, Birmingham, AL 35233, USA

Received: 01 November 2018 Accepted: 23 December 2018 Published: 17 January 2019

The gastrointestinal microbiome is intrinsically linked to the spread of antibiotic resistance. Antibiotic treatment puts patients at risk for colonization by opportunistic pathogens like vancomycin resistant Enterococcus and Clostridioides difficile by destroying the colonization resistance provided by the commensal microbiota. Once colonized, the host is at a much higher risk for infection by that pathogen. Furthermore, we know that microbiome community differences are associated with disease states, but we do not have a good understanding of how we can use these changes to classify different patient populations. To that end, we have performed a multicenter retrospective analysis on patients who received fecal microbiota transplants to treat recurrent Clostridioides difficile infection. We performed 16S rRNA gene sequencing on fecal samples collected as part of this study and used these data to develop a microbiome disruption index. Our microbiome disruption index is a simple index that is predictive across cohorts, indications, and batch effects. We are able to classify pre-fecal transplant vs post-fecal transplant samples in patients with recurrent C. difficile infection, and we are able to predict, using previously-published data from a cohort of patients receiving hematopoietic stem cell transplants, which patients would go on to develop bloodstream infections. Finally, we also identified patients in this cohort that were initially colonized with vancomycin resistant Enterococcus and that 92% (11/12) were decolonized after the transplant, but the microbiome disruption index was unable to predict such decolonization. We, however, were able to compare the relative abundance of different taxa between the two groups, and we found that increased abundance of Enterobacteriaceae predicts whether patients were colonized with vancomycin resistant Enterococcus. This work is an early step towards a better understanding of how microbiome predictors can be used to help improve patient care and patient outcomes.
- microbiome,
- fecal microbiota transplant,
- Clostridioides difficile,
- vancomycin resistant Enterococcus
Citation: Marina Santiago, Lindsay Eysenbach, Jessica Allegretti, Olga Aroniadis, Lawrence J. Brandt, Monika Fischer, Ari Grinspan, Colleen Kelly, Casey Morrow, Martin Rodriguez, Majdi Osman, Zain Kassam, Mark B. Smith, Sonia Timberlake. Microbiome predictors of dysbiosis and VRE decolonization in patients with recurrent C. difficile infections in a multi-center retrospective study[J]. AIMS Microbiology, 2019, 5(1): 1-18. doi: 10.3934/microbiol.2019.1.1

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Abstract

The gastrointestinal microbiome is intrinsically linked to the spread of antibiotic resistance. Antibiotic treatment puts patients at risk for colonization by opportunistic pathogens like vancomycin resistant Enterococcus and Clostridioides difficile by destroying the colonization resistance provided by the commensal microbiota. Once colonized, the host is at a much higher risk for infection by that pathogen. Furthermore, we know that microbiome community differences are associated with disease states, but we do not have a good understanding of how we can use these changes to classify different patient populations. To that end, we have performed a multicenter retrospective analysis on patients who received fecal microbiota transplants to treat recurrent Clostridioides difficile infection. We performed 16S rRNA gene sequencing on fecal samples collected as part of this study and used these data to develop a microbiome disruption index. Our microbiome disruption index is a simple index that is predictive across cohorts, indications, and batch effects. We are able to classify pre-fecal transplant vs post-fecal transplant samples in patients with recurrent C. difficile infection, and we are able to predict, using previously-published data from a cohort of patients receiving hematopoietic stem cell transplants, which patients would go on to develop bloodstream infections. Finally, we also identified patients in this cohort that were initially colonized with vancomycin resistant Enterococcus and that 92% (11/12) were decolonized after the transplant, but the microbiome disruption index was unable to predict such decolonization. We, however, were able to compare the relative abundance of different taxa between the two groups, and we found that increased abundance of Enterobacteriaceae predicts whether patients were colonized with vancomycin resistant Enterococcus. This work is an early step towards a better understanding of how microbiome predictors can be used to help improve patient care and patient outcomes.

Acknowledgments

The microbiome disruption index was developed by OpenBiome with the assistance of Finch Therapeutics and the support of CDC (contract numbers 200-2016-91946 and 200-2016-91948).

Conflict of interest

MS, ZK, ST, and MBS are employees of Finch Therapeutics Group Inc. JRA consults for and had research support from Finch Therapeutics Group. AG is a consultant for Merck. The authors declare no conflicts of interest in this paper.

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