What is the pathogenesis of acute gastroenteritis?

Pathogenesis of Acute Gastroenteritis

Acute gastroenteritis results from infectious agents (viral, bacterial, or parasitic) that invade and inflame the gastrointestinal mucosa, triggering fluid secretion, impaired absorption, and accelerated intestinal transit through direct epithelial damage and immune-mediated mechanisms. 1

Primary Pathogenic Mechanisms

Microbial Invasion and Epithelial Disruption

• Viral pathogens (norovirus, rotavirus, adenovirus) directly infect and destroy intestinal epithelial cells, leading to villous atrophy and reduced absorptive surface area 1
• Bacterial pathogens employ multiple strategies: enterotoxin production (causing secretory diarrhea), direct mucosal invasion (causing inflammatory diarrhea), or cytotoxin release (causing cellular destruction) 1
• Bacterial toxins like Cytolethal distending toxin B (CdtB) produced by Campylobacter, Salmonella, and Shigella directly damage epithelial cells and trigger host antibody responses 1

Inflammatory Cascade Activation

• The innate immune system responds with mast cell and macrophage activation in the intestinal mucosa, releasing pro-inflammatory mediators 1
• Pro-inflammatory cytokines (IL-1β, IFN-γ) are upregulated while anti-inflammatory cytokines (IL-10, IL-13) are suppressed during acute infection 1
• Adaptive immunity mobilizes with increased T lymphocyte infiltration into the lamina propria and epithelium, amplifying the inflammatory response 1

Barrier Dysfunction and Permeability Changes

• Acute infection causes increased intestinal permeability as measured by lactulose-mannitol ratios, allowing fluid and electrolyte loss 1
• Tight junction disruption permits bacterial translocation and systemic inflammatory responses in severe cases 1
• The protective commensal microbiota undergoes profound depletion, removing competitive inhibition against pathogens 2

Pathogen-Specific Mechanisms

Viral Gastroenteritis

• Norovirus (58% of foodborne gastroenteritis cases) requires only 10-100 viral particles for transmission and causes direct epithelial cell destruction with 12-48 hour incubation 1
• Rotavirus (historically most common in children <5 years before vaccination) infects enterocytes causing villous blunting and malabsorption 1
• Viral shedding continues for 1-3 weeks after symptom resolution, maintaining transmission risk 1

Bacterial Gastroenteritis

• Salmonella enterica (11% of foodborne cases, 35% of hospitalizations) invades intestinal mucosa and can cause bacteremia, particularly in immunocompromised hosts 1
• Campylobacter (28% of bacterial cases in children) produces inflammatory diarrhea through mucosal invasion and toxin production 1
• Shigella (21% of bacterial cases) causes dysentery through direct epithelial invasion and Shiga toxin production 1

Enteroendocrine and Neuromuscular Alterations

• Enterochromaffin (EC) cell counts increase during acute infection, particularly with Campylobacter, leading to elevated serotonin (5-HT) production 1
• Increased 5-HT stimulates intestinal secretion and accelerates motility through enteric nervous system activation 1
• Mast cell-nerve fiber interactions increase in the terminal ileum, contributing to visceral hypersensitivity and altered motility 1

Microbiota Disruption

• Acute infection causes depletion of commensal bacteria, particularly beneficial species like Subdoligranulum variabile and Eubacterium limosum 1
• Loss of microbial diversity correlates with increased lymphocyte infiltration and prolonged immune activation 1
• Pathogenic bacteria stimulate IL-1β production while suppressing IL-10 release, creating a pro-inflammatory cytokine environment 1

Clinical Manifestations Based on Pathogenesis

• Watery diarrhea results from enterotoxin-mediated secretion or viral-induced malabsorption without significant mucosal invasion 1
• Bloody diarrhea (dysentery) indicates invasive bacterial pathogens causing direct mucosal destruction and inflammatory exudate 1
• Vomiting predominates with viral pathogens and toxin-producing bacteria affecting the upper GI tract 1, 2

Host Susceptibility Factors

• Immunocompromised patients experience more severe and prolonged courses due to impaired cellular immunity against viral and bacterial pathogens 1, 2
• Children <5 years and elderly >65 years have higher hospitalization and mortality rates despite lower overall incidence in elderly 1
• Psychological stress during infection may alter the cytokine milieu toward Th2 responses and influence disease severity 1

Common Pitfalls in Understanding Pathogenesis

• Not all diarrhea represents mucosal inflammation—toxin-mediated secretory diarrhea occurs without significant tissue invasion 1
• The severity of symptoms does not always correlate with the degree of mucosal damage visible on endoscopy 1
• Antibody responses to bacterial toxins (anti-CdtB, anti-vinculin) can persist long after acute infection resolves and may contribute to post-infectious sequelae 1