Caudovirales bacteriophages are associated with improved executive function and memory in flies, mice, and humans.
Level 4 - case-series / case-control
Cross-sectional human observational cohorts combined with preclinical animal and insect experiments.
PubMed 35176247 · doi:10.1016/j.chom.2022.01.013
What was done
The authors evaluated associations between gut bacteriophage composition (specifically Caudovirales, Siphoviridae, and Microviridae) and cognitive performance across a human discovery cohort (n = 114) and a validation cohort (n = 942), measuring executive function and verbal memory. To explore mechanisms, they performed fecal microbiota transplantation from human donors with elevated Caudovirales levels (>90% Siphoviridae) into mice to test novel object recognition and prefrontal cortex immediate early gene expression. They also supplemented Drosophila diets with the 936 group of lactococcal Siphoviridae bacteriophages to test memory scores and brain gene expression.
What was found
In both human cohorts, elevated Caudovirales and Siphoviridae levels correlated with better executive performance and verbal memory, whereas higher Microviridae levels were associated with greater executive impairment. In mice, human fecal transplantation enriched in Caudovirales increased novel object recognition scores and up-regulated memory-promoting immediate early genes in the prefrontal cortex. In Drosophila, lactococcal Siphoviridae supplementation improved memory scores and up-regulated memory-related brain genes. No exact numerical estimates, effect sizes, or p-values were reported in the abstract.
Why it matters
This study extends the microbiome-gut-brain axis to the gut virome, suggesting that specific bacteriophages may modulate cognitive function across species.
Limits
The human evidence is observational/cross-sectional, precluding direct causal inference in humans, and confounding from bacterial host shifts or diet cannot be excluded from the abstract alone. No numerical effect sizes, test statistics, or variance estimates are reported in the abstract. Interventional phage supplementation was tested only in model organisms (flies and mice).
Cited by
- supports Higher levels of specific bacteriophages in the human gut are associated with better cognitive executive function.
- supports Transplanting fecal material from humans with high levels of cognitive-associated gut bacteriophages into mice improves executive and memory function in the mice.