Remarkable preprint by a team that includes Caterina Gasperini and Lee Rubin

Remarkable preprint by a team that includes Caterina Gasperini and Lee Rubin of Harvard Medical School: the title "Microbiome depletion rejuvenates the aging brain" is click-baity (and misleading: DO NOT TRY THIS AT HOME) but the substance of the work is fascinating, confirming what researchers have suspected for some time: the gut-brain axis, either direct (e.g., vagus nerve) or indirect (e.g., circulating molecules coming from the gut) is involved in brain aging and probably in neurodegenerative diseases.

To show the impact of the gut microbiota on brain aging, they basically wiped out most of the microbial ecosystem with antibiotics in mice, which improved vascular density, promoted myelination, enhanced neurogenesis, and reduced microglial reactivity. "Functionally, microbiome-depleted mice showed improved hippocampal memory performance. Analyses of brain and plasma cytokine levels showed a decrease in several pro-inflammatory factors post-treatment and identified candidate factors, including the chemokine eotaxin-1. Inhibiting eotaxin-1 alone can reverse several aspects of brain aging."

Again, this is not an endorsement of antibiotic-based microbial depletion: it was used as a tool in mice to prove a causal effect. And it worked. But depleting your gut microbial ecosystem has a lot of adverse consequences -it has co-evolved with humans for a reason. I would take away the more reasonable message from the paper's abstract:

"age-associated microbial inflammation contributes to brain aging and that its attenuation can restore youthful features at the molecular, cellular, and functional levels. Targeting the gut microbiome or its circulating mediators may therefore represent a non-invasive approach to promote brain health and cognitive resilience in aging."

I am biased toward "circulating mediators", in particular LPS, but the general message is proven beyond doubt: a bad gut makes the brain age faster.

Figure below is stunning: legend, partially italicized for effect "Microbiome depletion enhances adult neurogenesis in aged mice"

https://www.biorxiv.org/content/10.64898/2026.02.13.705770v1.full.pdf