TY - JOUR

T1 - Bacteriophage-mediated manipulation of the gut microbiome - promises and presents limitations

AU - Rasmussen, Torben Sølbeck

AU - Koefoed, Anna Kirstine

AU - Jakobsen, Rasmus Riemer

AU - Deng, Ling

AU - Castro-Mejía, Josué L.

AU - Brunse, Anders

AU - Neve, Horst

AU - Vogensen, Finn Kvist

AU - Nielsen, Dennis Sandris

PY - 2020

Y1 - 2020

N2 - Gut microbiome (GM) composition and function are linked to human health and disease, and routes for manipulating the GM have become an area of intense research. Due to its high treatment efficacy, the use of fecal microbiota transplantation (FMT) is generally accepted as a promising experimental treatment for patients suffering from GM imbalances (dysbiosis), e.g. caused by recurrent Clostridioides difficile infections (rCDI). Mounting evidence suggests that bacteriophages (phages) play a key role in successful FMT treatment by restoring the dysbiotic bacterial GM. As a refinement to FMT, removing the bacterial component of donor feces by sterile filtration, also referred to as fecal virome transplantation (FVT), decreases the risk of invasive infections caused by bacteria. However, eukaryotic viruses and prophage-encoded virulence factors remain a safety issue. Recent in vivo studies show how cascading effects are initiated when phage communities are transferred to the gut by e.g. FVT, which leads to changes in the GM composition, host metabolome, and improve host health such as alleviating symptoms of obesity and type-2-diabetes (T2D). In this review, we discuss the promises and limitations of FVT along with the perspectives of using FVT to treat various diseases associated with GM dysbiosis.

AB - Gut microbiome (GM) composition and function are linked to human health and disease, and routes for manipulating the GM have become an area of intense research. Due to its high treatment efficacy, the use of fecal microbiota transplantation (FMT) is generally accepted as a promising experimental treatment for patients suffering from GM imbalances (dysbiosis), e.g. caused by recurrent Clostridioides difficile infections (rCDI). Mounting evidence suggests that bacteriophages (phages) play a key role in successful FMT treatment by restoring the dysbiotic bacterial GM. As a refinement to FMT, removing the bacterial component of donor feces by sterile filtration, also referred to as fecal virome transplantation (FVT), decreases the risk of invasive infections caused by bacteria. However, eukaryotic viruses and prophage-encoded virulence factors remain a safety issue. Recent in vivo studies show how cascading effects are initiated when phage communities are transferred to the gut by e.g. FVT, which leads to changes in the GM composition, host metabolome, and improve host health such as alleviating symptoms of obesity and type-2-diabetes (T2D). In this review, we discuss the promises and limitations of FVT along with the perspectives of using FVT to treat various diseases associated with GM dysbiosis.

KW - bacteriophages

KW - cascading effects

KW - dysbiosis

KW - fecal virome transplantation

KW - gut microbiome

KW - phage therapy

U2 - 10.1093/femsre/fuaa020

DO - 10.1093/femsre/fuaa020

M3 - Review

C2 - 32495834

AN - SCOPUS:85088881452

VL - 44

SP - 507

EP - 521

JO - F E M S Microbiology Reviews

JF - F E M S Microbiology Reviews

SN - 0168-6445

IS - 4

ER -