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Control of Infection by Defined Microbial Communities

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  • Authors: James Collins1, Jennifer M. Auchtung2
  • Editors: Robert Allen Britton3, Patrice D. Cani4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Alkek Center for Metagenomics and Microbiome Research and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030; 2: Alkek Center for Metagenomics and Microbiome Research and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030; 3: Baylor College of Medicine, Houston, TX 77030; 4: Université catholique de Louvain, Louvain Drug Research Institute, Brussels 1200, Belgium
  • Source: microbiolspec September 2017 vol. 5 no. 5 doi:10.1128/microbiolspec.BAD-0009-2016
  • Received 25 July 2016 Accepted 17 July 2017 Published 22 September 2017
  • Jennifer Auchtung, jennifer.auchtung@bcm.edu
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  • Abstract:

    Each year in the United States, billions of dollars are spent combating almost half a million infections (CDIs) and trying to reduce the ∼29,000 patient deaths in which has an attributed role. In Europe, disease prevalence varies by country and level of surveillance, though yearly costs are estimated at €3 billion. One factor contributing to the significant health care burden of is the relatively high frequency of recurrent CDIs. Recurrent CDI, i.e., a second episode of symptomatic CDI occurring within 8 weeks of successful initial CDI treatment, occurs in ∼25% of patients, with 35 to 65% of these patients experiencing multiple episodes of recurrent disease. Using microbial communities to treat recurrent CDI, either as whole fecal transplants or as defined consortia of bacterial isolates, has shown great success (in the case of fecal transplants) or potential promise (in the case of defined consortia of isolates). This review will briefly summarize the epidemiology and physiology of infection, describe our current understanding of how fecal microbiota transplants treat recurrent CDI, and outline potential ways that knowledge can be used to rationally design and test alternative microbe-based therapeutics.

  • Citation: Collins J, Auchtung J. 2017. Control of Infection by Defined Microbial Communities. Microbiol Spectrum 5(5):BAD-0009-2016. doi:10.1128/microbiolspec.BAD-0009-2016.

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/content/journal/microbiolspec/10.1128/microbiolspec.BAD-0009-2016
2017-09-22
2017-12-15

Abstract:

Each year in the United States, billions of dollars are spent combating almost half a million infections (CDIs) and trying to reduce the ∼29,000 patient deaths in which has an attributed role. In Europe, disease prevalence varies by country and level of surveillance, though yearly costs are estimated at €3 billion. One factor contributing to the significant health care burden of is the relatively high frequency of recurrent CDIs. Recurrent CDI, i.e., a second episode of symptomatic CDI occurring within 8 weeks of successful initial CDI treatment, occurs in ∼25% of patients, with 35 to 65% of these patients experiencing multiple episodes of recurrent disease. Using microbial communities to treat recurrent CDI, either as whole fecal transplants or as defined consortia of bacterial isolates, has shown great success (in the case of fecal transplants) or potential promise (in the case of defined consortia of isolates). This review will briefly summarize the epidemiology and physiology of infection, describe our current understanding of how fecal microbiota transplants treat recurrent CDI, and outline potential ways that knowledge can be used to rationally design and test alternative microbe-based therapeutics.

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Figures

Image of FIGURE 1
FIGURE 1

Cumulative number of articles in PubMed. Total article number includes all articles with “difficile” in either the title or abstract. *Ribotype articles are those that have “difficile” and the ribotype (or alternative nomenclature) in the title or abstract; e.g., RT027 articles were classified as such if they had “difficile” AND “Ribotype 027” OR “RT027” OR “Sequence Type 1” OR “NAP1” etc. Although not a definitive measure of global ribotype abundance, these data can serve as a proxy for the relative frequency of outbreaks associated with specific ribotypes.

Source: microbiolspec September 2017 vol. 5 no. 5 doi:10.1128/microbiolspec.BAD-0009-2016
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Image of FIGURE 2
FIGURE 2

Under normal circumstances the gastrointestinal tract is able to resist infection by . This is thought to be accomplished by a combination of factors mediated by the host and colonization resistance due to the indigenous microbiota. These mechanisms, expanded on in the main text, include (i) competition for nutrients and their conversion into metabolites inhibitory to , (ii) microbial conversion of primary to secondary bile salts such as deoxycholate which can induce germination of spores but prevent the growth of vegetative , (iii) production of antimicrobial peptides and bacteriocins by the host microbiota, and (iv) a balanced host immune response that includes production of immunoglobulins, accumulation of protective iTreg cells in the lamina propria, and release of anti-inflammatory cytokines. Upon disruption of these resistance mechanisms, primarily through antibiotic use, there is an accumulation of proinflammatory Th17 cells and a reduction in bacterial diversity. In this state is able to invade and proliferate, causing toxin-mediated damage to the epithelium. In many cases, following suitable antibiotic treatment for CDI the indigenous microbiota is able to recover and reestablish colonization resistance. However, in a significant number of cases this does not occur and patients are liable to suffer relapse. FMT has been shown to be remarkably successful for treating these patients, likely because multiple facets of colonization resistance are restored.

Source: microbiolspec September 2017 vol. 5 no. 5 doi:10.1128/microbiolspec.BAD-0009-2016
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Tables

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TABLE 1

Stratification of disease severity associated with colonization ( 44 , 45 )

Source: microbiolspec September 2017 vol. 5 no. 5 doi:10.1128/microbiolspec.BAD-0009-2016
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TABLE 2

Results of FMT in severely ill patients

Source: microbiolspec September 2017 vol. 5 no. 5 doi:10.1128/microbiolspec.BAD-0009-2016
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TABLE 3

Comparison of rates of success and adverse events as a function of route of delivery for FMT

Source: microbiolspec September 2017 vol. 5 no. 5 doi:10.1128/microbiolspec.BAD-0009-2016

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