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Study breakdown

Neuropeptide Substance P Protects Against Colitis and Anxiety Through Gut-Brain Axis

evidence
The takeaway

Neuropeptide substance P (SP) protected against colitis and associated anxiety-like behavior through gut-brain axis modulation, revealing SP as a protective factor in inflammatory bowel disease.

Gut AND mind protector

Substance P — traditionally viewed as pro-inflammatory — actually protects against both colitis and the anxiety that accompanies it

What the researchers found

SP protected against colitis and anxiety-like behavior through gut-brain axis modulation, challenging its traditional pro-inflammatory characterization and revealing protective roles in IBD.

Why it matters

IBD patients frequently suffer from anxiety/depression. A neuropeptide protecting against both gut inflammation and anxiety addresses the gut-brain connection.

How the study worked

Colitis model with SP pathway investigation, assessment of intestinal inflammation and anxiety-like behavior.

What this study cannot tell us

Preclinical colitis model.

How to read the evidence

Preclinical mechanistic study.

When this study was published

Published in 2025.

The bigger picture

SP's dual gut-brain protective role reframes this well-known neuropeptide and could inform new IBD+mental health treatment strategies.

Questions still open

  • Would SP agonists improve IBD outcomes and mental health simultaneously?
  • Does SP deficiency contribute to IBD-associated anxiety?
  • How does SP protection reconcile with its known pro-inflammatory roles?

Common questions

Can a pain peptide protect the gut?
Surprisingly, yes. Substance P — known for pain signaling — actually protected against intestinal inflammation AND the anxiety that accompanies it, through the gut-brain axis.
Why does gut disease cause anxiety?
The gut and brain are connected by neuropeptide signaling. Substance P modulates both systems simultaneously, explaining how gut inflammation can trigger mental health problems — and how protecting the gut also protects the mind.

Read the original research

Neuropeptide SP protects against colitis and linked anxiety-like behavior through the putative roles of gut microbiota and metabolite inositol.

Nature communications, 17(1), 295

Citation

Lan, Jing; Wang, Jiaqi; Huang, Sijuan; Li, Chenyu; Deng, Ziteng; Hao, Zhihui; Ma, Yunfei. (2026). Neuropeptide SP protects against colitis and linked anxiety-like behavior through the putative roles of gut microbiota and metabolite inositol.. Nature communications, 17(1), 295. https://doi.org/10.1038/s41467-025-67904-0