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

ABSTRACT

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.

KEYWORDS:

• Fecal virome transplantation
• Gut microbiome
• Fertility
• Probiotic engraftment
• Lacticaseibacillus rhamnosus
• Akkermansia muciniphila

Acknowledgments

We thank the animal caretakers Helene Farlov and Mette Nelander at Section of Experimental Animal Models (University of Copenhagen, Denmark) for taking care of the animals during the study and assisting with the animal handling.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

TSR, CMJM, AKH, and DSN conceived the research idea and designed the study; TSR, CMJM, MRD, LSFZ, performed the experiments TSR, CMJM, MRD, RRJ, LSFZ, JLCM, AB, CHFH, LHH, AKH, and DSN performed laboratory and data analysis; TSR wrote the first draft of the manuscript. All authors critically revised and approved the final version of the manuscript.

Data availability statement

Raw sequencing data can be accessed at ENA with project ID: PRJEB52388 (https://www.ebi.ac.uk/ena/browser/).

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2208504

Additional information

Funding

Funding was provided by the Danish Council for Independent Research with grant ID: DFF-6111-00316 “PhageGut” (www.phagegut.ku.dk).