Antibiotics in PANS

How Antibiotics May Help in PANS/PANDAS: Beyond Infection Control

In Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections), antibiotics often seem to calm symptoms like obsessive-compulsive behaviors, anxiety, and tics. Traditionally, this benefit has been credited to the eradication of Streptococcus pyogenes or other presumed bacterial trigger.

Yet clinical experience shows that improvement sometimes occurs even when no active infection is found — and may fade over time despite continued antibiotics. This suggests that antibiotics may influence the underlying immune environment in more complex ways, particularly through effects on the gut microbiome.

1. The Classic Explanation: Removing the Trigger

The best-known theory in PANDAS is molecular mimicry: antibodies raised against streptococcal antigens mistakenly cross-react with neuronal tissue in the basal ganglia, causing neuroinflammation and abrupt behavioral change.

Antibiotics such as penicillin, amoxicillin, or azithromycin can decrease S. pyogenes, thereby removing the antigenic stimulus. Several studies and clinical series describe improvement with antimicrobial treatment or prophylaxis, particularly in children with documented recurrent strep infections. However, antibiotics sometimes help even when throat cultures are negative — implying other mechanisms at play.

2. A Second Mechanism: Resetting the Microbiome–Immune Axis

Antibiotics profoundly reshape the gut microbial community within days. In animal and human studies, these shifts have been shown to influence systemic inflammation, brain immune activity, and behavior.

When gut bacteria are reduced or rebalanced:

• Inflammatory signaling (perhaps through microbial components like LPS) can drop.

• Short-chain fatty acids (SCFAs) — particularly butyrate, a key anti-inflammatory metabolite — may fluctuate, altering microglial activation in the brain.

• T-regulatory immune tone can shift, dampening the hyperinflammatory responses characteristic of PANS/PANDAS.

Rodent experiments support this link. For example, Bercik et al. found that antibiotics altered gut flora and anxiety-like behavior, which could be reversed by restoring normal microbiota. Many studies illustrate a plausible mechanism: that antibiotics change gut ecology, which modulates immune and neuroimmune signaling, leading to temporary relief of inflammation-driven psychiatric symptoms.

3. Why the Benefit Sometimes Wears Off

If the initial improvement stems partly from microbiome modulation, it makes sense that the effect might fade. Over time, antibiotic pressure can:

• Select for resistant or pro-inflammatory species.

• Allow fungal or opportunistic bacterial overgrowth.

• Reduce beneficial species that normally produce SCFAs and maintain gut barrier integrity.

As microbial diversity narrows, systemic inflammation may gradually re-emerge, and the neuropsychiatric symptoms return — even if the original infection remains absent.

4. Implications for Treatment

Recognizing the microbiome’s role doesn’t negate antibiotics’ usefulness but reframes them as a double-edged tool. For some children, a short antibiotic course may break an inflammatory cycle; for others, prolonged exposure can perpetuate dysbiosis and instability.After antibiotics, strategies that restore microbial balance —fermented foods, diets low in processed foors (esp white flour, white sugar, and white milk), or specific diets (eg gluten free) may help sustain the shift in the microbiome for sustained improvement. Controlled clinical trials are still needed, but this integrative model aligns with what many clinicians observe at the bedside.

5. The Takeaway

Antibiotics in PANS/PANDAS likely act through more than just germ-killing. By reshaping the gut microbiome and, in turn, the immune signals that reach the brain, they can transiently shift the inflammatory tone that drives symptoms. Understanding and supporting that microbiome-immune-brain connection may be key to achieving more durable recovery — with or without ongoing antibiotics.