Chronic stress remodels gut bacterial ecology and polysaccharide metabolism with neuroendocrine consequences despite unchanged behavior
- 1Baylor University
Abstract
The gut-microbiome-brain axis (GMBA) links the gut and brain through metabolic, immunological, and neuroendocrine pathways, and can become dysregulated during psychological stress (PS). While previous studies primarily infer microbial function and use physical stressors that incompletely model human PS, here, functional multi-omics was applied to a chronic social-isolation mouse model. Although isolation caused no measurable behavioral changes, brain proteomics revealed stress-associated molecular responses. Taxonomic and short-chain fatty acid analyses suggested limited microbiome changes; however, metaproteomics uncovered sex-specific restructuring of bacterial ecology and carbohydrate-active enzymes. In females, isolation increased Petralouisia muris proteins involved in bacterial microcompartment metabolism and {beta}-glucuronidases across Lachnospiraceae taxa. Enriched {beta}-glucuronidase abundance coincided with reduced circulating glucuronides and altered brain estrogen-receptor activity, suggesting a microbial deconjugation-host estrogen-signaling interaction. These findings demonstrate that functional GMBA alterations may precede or occur independently of overt behavioral phenotypes and highlight the value of direct functional profiling in PS.
Related
- Stochasticity in Metabolism: Oxidative Stress Response Phenotypes As Emergent Consequences of Network Topology
- Genes controlling polysaccharide synthesis, protein folding and basic metabolism ensure intra-host cell adaptation and replication of Yersinia enterocolitica
- Temperature drives transcriptomic shifts in amphibian skin bacterial communities with consequences for fungal pathogen control
- MeSRT1 Interacts with MeNF-YC15 and Negatively Mediates Resistance to Cassava Bacterial Blight via Regulation of Gibberellin Metabolism in Manihot esculenta Crantz
- A domesticated prophage enzyme links bacterial metabolism, episymbiosis and phage fitness
BibTeX
@misc{slusser2026chronic,
title = {{Chronic stress remodels gut bacterial ecology and polysaccharide metabolism with neuroendocrine consequences despite unchanged behavior}},
author = {A. C. Slusser and T. R. Relangi and L. A. Hudson and D. T. Le and M. M. Hernandez and T. J. Earp and A. T. Wright},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.757984},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757984v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Chronic stress remodels gut bacterial ecology and polysaccharide metabolism with neuroendocrine consequences despite unchanged behavior
AU - A. C. Slusser
AU - T. R. Relangi
AU - L. A. Hudson
AU - D. T. Le
AU - M. M. Hernandez
AU - T. J. Earp
AU - A. T. Wright
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.757984
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.757984v1
AB - The gut-microbiome-brain axis (GMBA) links the gut and brain through metabolic, immunological, and neuroendocrine pathways, and can become dysregulated during psychological stress (PS). While previous studies primarily infer microbial function and use physical stressors that incompletely model human PS, here, functional multi-omics was applied to a chronic social-isolation mouse model. Although isolation caused no measurable behavioral changes, brain proteomics revealed stress-associated molecular responses. Taxonomic and short-chain fatty acid analyses suggested limited microbiome changes; however, metaproteomics uncovered sex-specific restructuring of bacterial ecology and carbohydrate-active enzymes. In females, isolation increased Petralouisia muris proteins involved in bacterial microcompartment metabolism and {beta}-glucuronidases across Lachnospiraceae taxa. Enriched {beta}-glucuronidase abundance coincided with reduced circulating glucuronides and altered brain estrogen-receptor activity, suggesting a microbial deconjugation-host estrogen-signaling interaction. These findings demonstrate that functional GMBA alterations may precede or occur independently of overt behavioral phenotypes and highlight the value of direct functional profiling in PS.
ER -