Alteration of Gut Microbial Ecology by the Direct Activation of the Brain: Inverse Gut-Microbiome-Brain Dynamics

Authors

• I-Ching Wang
• Jessica L Swanson
• Jillian L Waters
• Mikhail Y Kochukov
• Shelly A Buffington
• Sean W Dooling
• Benjamin R Arenkiel
• Mauro Costa-Mattioli

Language

English

Publication Date

11-21-2025

Journal

iScience

DOI

10.1016/j.isci.2025.113709

PMID

41234770

PMCID

PMC12605924

PubMedCentral® Posted Date

10-9-2025

PubMedCentral® Full Text Version

Post-print

Abstract

The gut-microbiome-brain axis is a bidirectional communication system influencing host physiology and overall fitness. While "bottom-up" effects-where gut microbes influence brain function and behavior-are well established, direct evidence for "top-down" modulation-where the brain shapes the gut microbial ecology-remains elusive. Here, we show that the selective expression of the bacterial ion channel mNaChBac in glutamatergic lateral habenula (LHb) neurons increases their bursting activity and leads to endophentypes associated with depression. Importantly, this chronic activation leads to changes in the gut microbiome composition over time, as reflected by shifts in alpha-diversity and alterations in specific microbial taxa. These findings provide direct evidence that the persistent activation of the brain acts as a selective pressure that affects the stability and diversity of the gut microbiome, providing a new dimension by which gut-microbiome-brain interactions may cooperate to modulate host physiology and health.

Keywords

Neuroscience, Microbiology, Microbiome

Published Open-Access

yes

Recommended Citation

Wang, I-Ching; Swanson, Jessica L; Waters, Jillian L; et al., "Alteration of Gut Microbial Ecology by the Direct Activation of the Brain: Inverse Gut-Microbiome-Brain Dynamics" (2025). Faculty, Staff and Students Publications. 7266.
https://digitalcommons.library.tmc.edu/baylor_docs/7266