Objective Development of obesity and type 2 diabetes (T2D) are associated with gut microbiota (GM) changes. The gut viral community is predominated by bacteriophages (phages), which are viruses that attack bacteria in a host-specific manner. The antagonistic behaviour of phages has the potential to alter the GM. As a proof-of-concept, we demonstrate the efficacy of faecal virome transplantation (FVT) from lean donors for shifting the phenotype of obese mice into closer resemblance of lean mice.
Design The FVT consisted of viromes with distinct profiles extracted from the caecal content of mice from different vendors that were fed a low-fat (LF) diet for 14 weeks. Male C57BL/6NTac mice were divided into five groups: LF (as diet control), high-fat (HF) diet, HF+ampicillin (Amp), HF+Amp+FVT and HF+FVT. At weeks 6 and 7 of the study, the HF+FVT and HF+Amp+FVT mice were treated with FVT by oral gavage. The Amp groups were treated with Amp 24 hours prior to first FVT treatment.
Results Six weeks after first FVT, the HF+FVT mice showed a significant decrease in weight gain compared with the HF group. Further, glucose tolerance was comparable between the LF and HF+FVT mice, while the other HF groups all had impaired glucose tolerance. These observations were supported by significant shifts in GM composition, blood plasma metabolome and expression levels of genes associated with obesity and T2D development.
Conclusions Transfer of caecal viral communities from mice with a lean phenotype into mice with an obese phenotype led to reduced weight gain and normalised blood glucose parameters relative to lean mice. We hypothesise that this effect is mediated via FVT-induced GM changes.
- diabetes mellitus
- gut differentiation
- intestinal microbiology
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Contributors TSR, CMJM, AKH, DSN and FKV conceived the research idea and designed the study; CMJM and TSR performed the animal experiments; TSR, CMJM and SZ processed the samples in the laboratory; TSR, CMJM, LHH, WK, DSN, JRS, SZ, JLC-M and FKV performed data analysis; TSR and DSN were responsible for the first and final drafts of the manuscript, as well as all requested revisions. All authors critically revised and approved the final version of the manuscript.
Funding Funding was provided by the Danish Council for Independent Research (grant ID: DFF-6111-00316) (PhageGut) and the Danish Innovation Fund project (7076-00129B), MICROHEALTH.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available in a public open access repository. All data relevant to the study are included in the article or uploaded as supplementary information. Raw DNA sequencing data is available at European Nucleotide Archive (ENA) with accession PRJEB32560 (https://www.ebi.ac.uk/ena/data/view/PRJEB32560). The data includes raw demultiplexed Illumina sequencing reads of 16S rRNA amplicons and metaviromes. The remaining data sheets are available upon reasonable request.