Getting to the Guts of it all! Part 2

In this article, we dive deeper into the mechanics of how the gut is directly impacted by a concussion injury…

Let me tell you why I think gut function and the microbiome is absolutely crucial to address in concussion injuries, and why skipping this is a highway to long-term risks as a result of ongoing inflammatory processes. Within 6 hours of a concussion, a cascade of neurological and inflammatory processes disrupts intestinal barrier function through the following mechanisms. 6 hours! Now, in my experience, a huge portion of the population already have some degree of gut dysfunction for a myriad of reasons, making it even more important to prioritize gut health, microbial diversity and barrier integrity as a preventative meausre also! Here are some of the things that are happening in the gut on concussion injury

Concussion triggers a rapid cascade of events that disrupt intestinal barrier integrity through interconnected pathways

1. Inflammatory Cascade

• TNF-α surge: Brain injury triggers an immediate release of pro-inflammatory cytokines like TNF-α, which directly disrupt intestinal tight junctions - intestinal permeability aka leaky gut is immediately in the picture.

• Tight junction breakdown: TNF-α reduces expression of key proteins (Claudins, Occludin, ZO-1) that seal intestinal epithelial cells, creating gaps up to 0.25 μm in size—large enough for bacteria like E. coli species to translocate.

2. Neuroendocrine Activation

• Sympathetic nervous system (SNS) overdrive: The brain injury activates the SNS, releasing norepinephrine. This:

  • Reduces intestinal blood flow via vasoconstriction

  • Alters gut motility and mucus production

• HPA axis activation: Releases cortisol and norepinephrine, which impair mucosal repair mechanisms and promote apoptosis in intestinal epithelial cells.

3. Structural Gut Changes

• Paracellular permeability: ileal permeability increases within 6 hours post-injury, with:

  • Villous shortening and epithelial shedding observed microscopically

  • Upregulation of myosin light chain kinase (MLCK), which destabilizes tight junctions

  • Tight Junction Breakdown: TNF-α and interleukin-6 (IL-6) downregulate Claudins and Occludin, while MLCK disrupts the cytoskeletal anchoring of these proteins16.

  • Epithelial Damage: Apoptosis of intestinal cells occurs within hours, further thinning the protective mucosal layer6.

4. Microbial Shifts

• Dysbiosis onset: The microbial species that inhabit the microbiome are disrupted

• Pathogen Proliferation: Beneficial bacteria (Eubacterium rectale) decline, while gram-negative bacteria (e.g., Enterobacteriaceae) proliferate, releasing substances that exacerbate inflammation

• LPS Translocation: LPS enters systemic circulation through intestinal gaps, binding toll-like receptor 4 (TLR4) to amplify neuroinflammation.

Consequences by 24 hours post-injury:

• Bacterial endotoxins (e.g., LPS) enter systemic circulation, triggering secondary neuroinflammation

• Oxidative stress increases, creating a self-perpetuating cycle of gut-brain dysfunction

• Neuroinflammation feeds back to the gut via the vagus nerve, perpetuating dysbiosis and permeability

This rapid gut permeability explains why concussion patients often experience early gastrointestinal symptoms (nausea, vomiting) and highlights the critical window for therapeutic intervention.