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NIH grant 1R21AI202577-01: Antibiotic-Driven Campylobacter Immunogenicity and Microbiome Dysbiosis in Guillain-Barré Syndrome
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Byeonghwa Jeon. Award: $231000.
Start: 2026-08-21T00:00:00.
PROJECT SUMMARY
Standard antibiotic therapy may paradoxically increase the risk of Guillain–Barré syndrome (GBS), revealing a
critical gap in understanding treatment-related complications. GBS is an acute autoimmune neuropathy in
which immune responses targeting peripheral nerves cause rapidly progressive paralysis and respiratory
failure, leaving up to 20% of patients with permanent disability. Campylobacter jejuni is the leading infectious
trigger, accounting for one-quarter to one-half of all cases through molecular mimicry between bacterial
lipooligosaccharides (LOS) and peripheral nerve gangliosides. Several epidemiological studies suggest that
antibiotics increase GBS risk, creating a clinical dilemma due to the lack of evidence-based guidelines. We
have preliminary mechanistic evidence supporting this association. Antibiotic exposure significantly
upregulates LOS production in C. jejuni, a key antigenic determinant in GBS pathogenesis, and enhanced LOS
expression correlates with increased IL-8 secretion in epithelial cells. Elevated IL-8 is considered a potential
biomarker distinguishing GBS from chronic inflammatory demyelinating polyneuropathy (CIDP). Our prior
studies also showed that iron supplementation further increases LOS production, suggesting a synergistic role
for antibiotics and iron in enhancing bacterial immunogenicity. Moreover, clinical analyses of 112 GBS patients,
performed by our collaborators at the Peripheral Neuropathy Research Center in South Korea, revealed
profound microbiome dysbiosis: neuroprotective taxa were depleted, and pro-inflammatory organisms were
enriched. Notably, we observed distinct resistome alterations in GBS patients, which serve as molecular
signatures of prior antibiotic exposure. Based on our preliminary data, we hypothesize that antibiotics increase
GBS risk through a dual mechanism: enhancing C. jejuni LOS production while simultaneously disrupting the
gut microbiome in ways that favor inflammation over neuroprotection. Iron supplementation appears to amplify
these effects. Aim 1 will determine how therapeutic antibiotics enhance C. jejuni immunogenicity and
investigate if this translates into stronger anti-ganglioside antibody responses in antibiotic-exposed GBS
patients, leveraging our repository of serum samples from GBS patients. Aim 2 will characterize microbiome
composition changes and resistome profiles associated with antibiotic and iron exposure, defining molecular
signatures that predict GBS risk. This project addresses an unresolved clinical paradox with major implications
for the treatment of Campylobacter infections. By establishing mechanistic links between therapeutic
exposures and autoimmunity, our R21 will provide foundational evidence to refine prescribing guidelines and
inform strategies for other post-infectious autoimmune disorders. By establishing mechanistic links between
therapeutic exposures, bacterial immunogenicity, and host microbiome disruption, this project provides an
innovative framework for understanding how antibiotic use can inadvertently influence autoimmune risk.document fetched 2026-08-30 02:46