Long‐term microbiota and virome in a Zürich patient after fecal transplantation against <i>Clostridium difficile</i> infection

Broecker, Felix; Klumpp, Jochen; Moelling, Karin

doi:10.1111/nyas.13100

Cited by 39 publications

(60 citation statements)

References 112 publications

(257 reference statements)

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“…It is known that enteric phages normally influence the complexity of the host community 4,6,7 . The bacteria in the case described here indeed exhibited heterogeneity and variability, which stood in stark contrast to the phage community.…”

Section: Discussionmentioning

confidence: 67%

“…1b). Prolonged dysbiosis was an unusual characteristic of this case report, as the majority of rCDI patients have been reported to attain highly donor-similar bacterial communities within days or weeks following successful FMT 4 . Only after a longer period up to 4.5 years, bacterial communities have reached a highly donor-similar composition in the Zurich patient.…”

Section: Introductionmentioning

confidence: 63%

“…In the case reported here, the patient, due to month-long repeated antibiotic treatment, was likely deprived from most of the endogenous gut microbiota that was replenished by the donor's 12 . In a healthy microbiome/virome, phages are less abundant than during inflammatory diseases and predominantly exist as integrated prophages 4,9 . Since our sequencing approach included both free phages and prophages that we could not distinguish, DNA sequence information specifically from isolated VLPs 11,20 will be required to reveal whether free phage communities likewise exhibit donor similarity and stability following FMT as observed here.…”

Section: Discussionmentioning

confidence: 89%

“…However, it can be assumed that the patient's microbiota at that time was severely dysbiotic due to month-long antibiotic therapy prior to FMT 12 . It has been shown previously that antibiotic treatment against rCDI leads to an expansion of Proteobacteria and a depletion of Bacteroidetes and Firmicutes, 4 characteristics that were partially observed in the patient after FMT as well (Figs. 1b, c).…”

Section: Discussionmentioning

confidence: 89%

“…The 10 14 gut bacteria per individual 5 are conventionally considered the most relevant component of FMT. In contrast, the 10 times more numerous enteric viruses 6,7 have remained largely unexplored in this context 4,8 . The human gut virome is mainly composed of bacteriophages belonging to the Caudovirales order, which are tailed double-stranded (dsDNA) phages, and the ssDNA Microviridae family 9-11 but also harbors a diverse community of eukaryotic viruses 6 and probably giant viruses such as Chlorella viruses 4 with a poorly understood impact on health and disease.…”

Section: Introductionmentioning

confidence: 99%

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Stable core virome despite variable microbiome after fecal transfer

et al. 2016

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We recently described the 4.5-year time course of the enteric bacterial microbiota and virome of a patient cured from recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT). Here, we extended the virome analyses and found the patient's phage population to exhibit highly donor-similar characteristics following FMT, which remained stable for the whole period tested (up to 7 months). Moreover, the detected viral populations of donor and patient exhibited comparable diversity and richness. These findings were unexpected since enteric viromes are normally highly variable, assumed to influence the bacterial host community and change with environmental conditions. In contrast to the virome, the bacterial microbiota varied indeed for more than 7 months with ongoing dysbiosis before it reached donor similarity. Our findings that are based on sequence information and protein domain analysis seem to suggest that stable phage properties correlate with successful FMT better than the changing bacterial communities. We speculate that we here preferentially detected a stable core virome, which dominated over a variable flexible virome that may have been too heterogeneous for experimental detection or was underrepresented in the databases. It will be interesting to analyze whether the enteric virome allows predictions for the clinical outcome of FMT for rCDI and other diseases such as inflammatory bowel disease or obesity.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Stable core virome despite variable microbiome after fecal transfer

et al. 2016

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Epigenetic Treatment of Persistent Viral Infections

Moos¹,

Pinkert

Irwin

et al. 2016

Drug Development Research

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Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population. Exploring the population diversity of the human microbiome and the effects its compositional variances have on the immune system, health, and disease are the subjects of intense investigational research and study. Among the collection of viruses, bacteria, fungi, and single-cell eukaryotes that comprise the human microbiome, the virome has been grossly understudied relative to the influence it exerts on human pathophysiology, much as mitochondria have until recently failed to receive the attention they deserve, given their critical biomedical importance. Fortunately, cellular epigenetic machinery offers a wealth of druggable targets for therapeutic intervention in numerous disease indications, including those outlined above. With advances in synthetic biology, engineering our body's commensal microorganisms to seek out and destroy pathogenic species is clearly on the horizon. This is especially the case given recent breakthroughs in genetic manipulation with tools such as the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) gene-editing platforms. Tying these concepts together with our previous work on the microbiome and neurodegenerative and neuropsychiatric diseases, we suggest that, because mammalian cells respond to a viral infection by triggering a cascade of antiviral innate immune responses governed substantially by the cell's mitochondria, small molecule carnitinoids represent a new class of therapeutics with potential widespread utility against many infectious insults. Drug Dev Res 78 : 24-36, 2017. © 2016 Wiley Periodicals, Inc.

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Abnormal Intestinal Microbiome in Medical Disorders and Potential Reversibility by Fecal Microbiota Transplantation

et al. 2020

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Reduction in diversity of the intestinal microbiome (dysbiosis) is being identified in many disease states, and studies are showing important biologic contributions of microbiome to health and disease. Fecal microbiota transplantation (FMT) is being evaluated as a way to reverse dysbiosis in diseases and disorders in an attempt to improve health. The published literature was reviewed to determine the value of FMT in the treatment of medical disorders for which clinical trials have recently been conducted. FMT is effective in treating recurrent C. difficile infection in one or two doses, with many healthy donors providing efficacious fecal-derived products. In inflammatory bowel disease (IBD), FMT may lead to remission in approximately one-third of moderate-to-severe illnesses with one study suggesting that more durable FMT responses may be seen when used once medical remissions have been achieved. Donor products differ in their efficacy in treatment of IBD. Combining donor products has been one way to increase the potential value of FMT in treating chronic disorders. FMT is being explored in a variety of clinical settings affecting different organ systems outside CDI, with positive preliminary signals, in treatment of functional constipation, immunotherapy-induced colitis, neurodegenerative disease, as well as prevention of cancer-related disorders like graft versus host disease and decolonization of patients with recurrent urinary tract infection due to antibiotic-resistant bacteria. Currently, intense research is underway to see how the microbiome products like FMT can be harnessed for health benefits.

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Long‐term microbiota and virome in a Zürich patient after fecal transplantation against Clostridium difficile infection

Cited by 39 publications

References 112 publications

Stable core virome despite variable microbiome after fecal transfer

Stable core virome despite variable microbiome after fecal transfer

Epigenetic Treatment of Persistent Viral Infections

Abnormal Intestinal Microbiome in Medical Disorders and Potential Reversibility by Fecal Microbiota Transplantation

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