TY - JOUR

T1 - Fecal virome transfer improves proliferation of commensal gut Akkermansia muciniphila and unexpectedly enhances the fertility rate in laboratory mice

AU - Rasmussen, Torben Sølbeck

AU - Mentzel, Caroline M.Junker

AU - Danielsen, Malene Refslund

AU - Jakobsen, Rasmus Riemer

AU - Zachariassen, Line Sidsel Fisker

AU - Castro Mejia, Josue Leonardo

AU - Brunse, Anders

AU - Hansen, Lars Hestbjerg

AU - Hansen, Camilla Hartmann Friis

AU - Hansen, Axel Kornerup

AU - Nielsen, Dennis Sandris

N1 - Publisher Copyright: © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.

PY - 2023

Y1 - 2023

N2 - Probiotics are intended to improve gastrointestinal health when consumed. However, the probiotics marketed today only colonize the densely populated gut to a limited extent. Bacteriophages comprise the majority of viruses in the human gut virome and there are strong indications that they play important roles in shaping the gut microbiome. Here, we investigate the use of fecal virome transplantation (FVT, sterile filtrated feces) as a mean to alter the gut microbiome composition to lead the way for persistent colonization of two types of probiotics: Lacticaseibacillus rhamnosus GG (LGG) representing a well-established probiotic and Akkermansia muciniphila (AKM) representing a putative next-generation probiotic. Male and female C57BL/6NTac mice were cohoused in pairs from 4 weeks of age and received the following treatment by oral gavage at week 5 and 6: AKM+FVT, LGG+FVT, probiotic sham (Pro-sham)+FVT, LGG+Saline, AKM+Saline, and control (Pro-sham+Saline). The FVT donor material originated from mice with high relative abundance of A. muciniphila. All animals were terminated at age 9 weeks. The FVT treatment did not increase the relative abundance of the administered LGG or AKM in the recipient mice. Instead FVT significantly (p < 0.05) increased the abundance of naturally occurring A.muciniphila compared to the control. This highlights the potential of propagating the existing commensal “probiotics” that have already permanently colonized the gut. Being co-housed male and female, a fraction of the female mice became pregnant. Unexpectedly, the FVT treated mice were found to have a significantly (p < 0.05) higher fertility rate independent of probiotic administration. These preliminary observations urge for follow-up studies investigating interactions between the gut microbiome and fertility.

AB - Probiotics are intended to improve gastrointestinal health when consumed. However, the probiotics marketed today only colonize the densely populated gut to a limited extent. Bacteriophages comprise the majority of viruses in the human gut virome and there are strong indications that they play important roles in shaping the gut microbiome. Here, we investigate the use of fecal virome transplantation (FVT, sterile filtrated feces) as a mean to alter the gut microbiome composition to lead the way for persistent colonization of two types of probiotics: Lacticaseibacillus rhamnosus GG (LGG) representing a well-established probiotic and Akkermansia muciniphila (AKM) representing a putative next-generation probiotic. Male and female C57BL/6NTac mice were cohoused in pairs from 4 weeks of age and received the following treatment by oral gavage at week 5 and 6: AKM+FVT, LGG+FVT, probiotic sham (Pro-sham)+FVT, LGG+Saline, AKM+Saline, and control (Pro-sham+Saline). The FVT donor material originated from mice with high relative abundance of A. muciniphila. All animals were terminated at age 9 weeks. The FVT treatment did not increase the relative abundance of the administered LGG or AKM in the recipient mice. Instead FVT significantly (p < 0.05) increased the abundance of naturally occurring A.muciniphila compared to the control. This highlights the potential of propagating the existing commensal “probiotics” that have already permanently colonized the gut. Being co-housed male and female, a fraction of the female mice became pregnant. Unexpectedly, the FVT treated mice were found to have a significantly (p < 0.05) higher fertility rate independent of probiotic administration. These preliminary observations urge for follow-up studies investigating interactions between the gut microbiome and fertility.

KW - Akkermansia muciniphila

KW - Fecal virome transplantation

KW - Fertility

KW - Gut microbiome

KW - Lacticaseibacillus rhamnosus

KW - Probiotic engraftment

U2 - 10.1080/19490976.2023.2208504

DO - 10.1080/19490976.2023.2208504

M3 - Journal article

C2 - 37150906

AN - SCOPUS:85157966363

VL - 15

JO - Gut Microbes

JF - Gut Microbes

SN - 1949-0976

IS - 1

M1 - 2208504

ER -