Can gut infections cause autoimmune diseases?

Can Gut Infections Cause Autoimmune Diseases?

Yes, gut infections and gut microbial dysbiosis can trigger and drive systemic autoimmune diseases through multiple validated mechanisms including molecular mimicry, bacterial translocation, and immune dysregulation. 1

Evidence from Animal Models

The causal relationship between gut microbes and autoimmunity has been definitively proven in animal studies:

• Multiple inflammatory arthritis models remain completely healthy when raised in germ-free conditions, only developing disease when exposed to specific microbes. 1 This includes HLA-B27 transgenic rats, IL-1 receptor antagonist knockout mice, K/BxN T cell receptor transgenic mice, and SKG mice with ZAP-70 mutations.

• These data confirm that intestinal microbiota are required to trigger and drive systemic autoimmunity, not merely associated with it. 1

Mechanisms Linking Gut Infections to Autoimmunity

Molecular Mimicry

• Microbial proteins can cross-react with self-antigens, activating autoreactive T cells. 1 Examples include:
  • Mycobacterial heat-shock proteins mimicking cartilage epitopes in rheumatoid arthritis 1
  • Viral peptides (coronavirus 229E) activating T cells specific for myelin basic protein in multiple sclerosis 1
  • Epstein-Barr virus antigens mimicking lupus autoantigens 1

Bacterial Translocation

• Intestinal pathobionts can translocate across a disrupted gut barrier to trigger systemic autoimmunity. 1
  • Enterococcus gallinarum has been found in liver biopsies of systemic lupus erythematosus patients 1
  • Commensal bacterial orthologs of human autoantigens (like Ro60) can drive autoimmunity when they translocate 1

Immune Dysregulation

• Gut dysbiosis disrupts regulatory T cell function and promotes pro-inflammatory pathways. 2, 3
  • Beneficial bacteria like Faecalibacterium prausnitzii, Bifidobacterium, and Lactobacillus normally strengthen immune tolerance and reduce inflammation 2
  • Loss of these protective species allows expansion of pathobionts that trigger Th1 and Th17 inflammatory responses 1

Specific Autoimmune Diseases Linked to Gut Microbes

Rheumatoid Arthritis

• The most established microbiome-autoimmunity connection exists in rheumatoid arthritis, where microbes were identified as contributors as early as the 19th century. 1

Systemic Lupus Erythematosus

• SLE patients demonstrate decreased gut bacterial diversity, lower Firmicutes:Bacteroidetes ratio, and translocation of intestinal pathobionts. 1

Spondyloarthropathies

• Reactive arthritis develops after infection by enteropathogenic bacteria (described in 1916 by Fiessinger and Leroy). 1, 4
• Enteropathic arthritis is a direct sequela of inflammatory bowel disease and parallels colitis exacerbations. 1
• Ankylosing spondylitis shows distinct microbial signatures in terminal ileal biopsies. 1

Other Conditions

• Psoriatic arthritis demonstrates reduced Akkermansia and Ruminococcus correlating with higher intestinal IgA 1
• Primary biliary cirrhosis shows antibodies against microbial proteins 1

Clinical Implications

Risk Factors for Infection-Triggered Autoimmunity

• Genetic predisposition (particularly HLA associations) combined with environmental triggers creates autoimmune risk. 2
• Gut barrier disruption from poor diet, stress, antibiotics, or infections allows pathobiont translocation. 1
• Immunosuppressive medications (corticosteroids ≥20mg prednisolone for ≥2 weeks, thiopurines, anti-TNF agents) increase infection risk that can trigger autoimmunity. 1

Diagnostic Considerations

• When evaluating new-onset autoimmune symptoms, obtain history of recent gastrointestinal infections, antibiotic use, and dietary patterns 3, 5
• Post-streptococcal reactive arthritis occurs approximately 10 days after group A streptococcal pharyngitis with cumulative, persistent arthritis 4
• Monitor for cardiac involvement in post-streptococcal cases as progression to valvular disease can occur 4

Common Pitfalls

• Do not dismiss the temporal relationship between gut infections and autoimmune symptom onset - this connection is mechanistically validated, not coincidental 1, 3
• Recognize that dysbiosis (not just acute infection) can trigger autoimmunity through chronic low-grade inflammation and barrier disruption 1, 5
• Avoid overlooking secondary immunodeficiency states that alter both infection susceptibility and immune tolerance 2

Therapeutic Directions

• Emerging treatments aim to restore gut microbiome balance through targeted probiotics containing Faecalibacterium prausnitzii, Bifidobacterium, and Lactobacillus 2
• Novel approaches include low-dose IL-2 to expand regulatory T cells and mesenchymal stem cells to inhibit inflammatory responses 2
• Sulfasalazine may be considered for persistent reactive arthritis 4