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Calorie restriction & fasting
Research brief

Gut phage dynamics in diversity outbred mice across lifespan and under extreme calorie restriction

In a longitudinal study of 913 diversity outbred mice, most gut DNA phages tracked their host bacteria, consistent with 'piggyback-the-winner' dynamics; a subset changed with calorie restriction and aging, with lytic phages more common with age. [1]

Automatic summary · not editorially reviewed

The key findings

  1. The study was a large longitudinal study of 913 diversity outbred mice undergoing extreme dietary restriction, with detailed phenotypic characterization across lifespan. [1]

  2. After accounting for phage-bacterial covariation, a subset of phages changed in relative abundance and prevalence relative to their hosts in response to dietary restriction and aging. [1]

  3. Lytic phages became more common with aging, and phage richness decreased with age; both findings were previously observed in human cohorts. [1]

The source at a glance

Study type / format
Longitudinal metagenomic study in mice (abstract only)
Population / context
Diversity outbred mice (913 animals) undergoing extreme dietary restriction
Summary based on
Study abstract
Original publication
March 3, 2026

Longitudinal mouse cohort and viral genome assembly

The abstract describes a large longitudinal study of diversity outbred mice (913 animals) undergoing extreme dietary restriction, with detailed phenotypic characterization across lifespan. From 2997 longitudinal metagenomes, the researchers assembled 54,119 candidate DNA viral genomes, forming 6462 viral operational taxonomic units (vOTUs). Over 85% of vOTUs were annotated as novel. Viruses were annotated predominantly as prophages in the Caudoviricetes class. No eukaryotic DNA viruses and none of the strictly lytic Crassvirales order, which is abundant in the human gut, were detected.

Supporting source [1]

Phages mostly tracked host bacteria

The most prevalent phages had the widest predicted host ranges. The relative abundance of most phages was highly correlated with that of their inferred host bacteria, suggesting quiescent prophages dominate viral metagenomes, consistent with 'piggyback-the-winner' dynamics. After accounting for close phage-bacterial covariation, the researchers identified a subset of phages whose relative abundance and prevalence changed relative to their hosts in response to dietary restriction and aging. In particular, phages with larger genomes became less common in diets with restricted calories, potentially reflecting a higher fitness cost to their host. Generalist phages were enriched for a gene encoding a single-strand DNA binding protein reportedly involved in DNA repair and protection from nucleases encoded by host cells.

Supporting source [1]

Lytic phages and richness with aging

Lytic phages became more common with aging, and the researchers observed a reduction in phage richness with age; both findings were previously observed in human cohorts. The authors conclude that these studies enrich understanding of DNA phage dynamics in the gut while emphasizing the predominance of 'piggyback-the-winner' strategies.

Supporting source [1]

How to interpret this

This is an abstract only; the full text was not reviewed. The study was in diversity outbred mice, not humans, and the abstract reports no effect sizes, confidence intervals or statistical details. The findings describe associations and dynamics, not causes or human lifespan benefits.

Based on the study abstract; the full paper, tables and supplementary data were not reviewed.

Source & supporting passages

[1]
Dynamics of gut bacteriophage in diversity outbred mice studied over lifespan and during extreme caloric restriction.

Merenstein C, Litichevskiy L, Thaiss C, Collman RG, Bushman FD. · europepmc.org · March 3, 2026

Read the quoted passagesIn the language of the original source
  1. Finding 1 ↑

    large longitudinal study of diversity outbred mice
  2. Finding 2 ↑

    a subset of phages changing in relative
  3. Finding 3 ↑

    Lytic phages became more common with aging

AI-assisted summary with linked source passages. No independent editorial or clinical review.

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