Effects of fermented versus unfermented red cabbage on symptoms, immune response, inflammatory markers and the gut microbiome in young adults with allergic rhinoconjunctivitis: a randomised controlled trial protocol.

The trial is designed to enroll 158 participants with allergic rhinoconjunctivitis randomly assigned in a 1:1 ratio to fermented or unfermented red cabbage groups.

• Participants are young adults aged 18-35 years with allergic rhinoconjunctivitis (ARC).
• Random assignment is 1:1 between the fermented red cabbage intervention and the unfermented red cabbage control.
• The unfermented comparator is described as 'sensory-matched' to the fermented product.
• The study is single-centre and registered under DRKS00036475.

The primary outcome of the trial is change in Total Nose and Eye Symptom Score from baseline to week 8.

• The intervention period is 8 weeks of daily consumption of either fermented or unfermented red cabbage.
• The Total Nose and Eye Symptom Score captures the primary symptom burden of allergic rhinoconjunctivitis.
• This outcome is measured from baseline to week 8.

Secondary outcomes encompass a broad range of clinical, immunological, microbiological, and psychological measures.

• Daily symptoms and medication use will be captured via mobile ecological momentary assessments.
• Secondary outcomes include quality of life, psychological well-being, and gastrointestinal symptoms.
• Systemic inflammatory markers, total IgE, and immune cell profile will be assessed.
• Metagenomic characterisation of stool samples will be performed.
• A nested qualitative component will explore participants' experiences and acceptability of the intervention.

Statistical analyses will include mixed-effects models, time-series analyses incorporating daily pollen counts, and comprehensive microbiome statistics.

• Mixed-effects models will be used for primary and secondary outcome analyses.
• Time-series analyses will incorporate daily pollen counts as a contextual variable.
• Comprehensive microbiome statistics will be applied to metagenomic sequencing data.
• Safety outcomes and adverse events will also be assessed.

The study protocol is grounded in emerging evidence that fermented foods may modulate immune responses through live microbes and bioactive postbiotic metabolites relevant to allergic disease.

• Fermented foods may contain live microbes when unpasteurised or uncooked, as well as bioactive postbiotic metabolites.
• The gut microbiome is highlighted as playing a role in immune regulation and allergic disease.
• No prior randomised controlled trial has compared fermented versus unfermented red cabbage for allergic rhinoconjunctivitis.
• Allergic rhinoconjunctivitis is described as 'a highly prevalent immune-mediated condition associated with substantial symptom burden, impaired quality of life and increased healthcare use.'

The study was approved by the Ethics Committee of Charité-Universitätsmedizin Berlin and will follow open science practices for data sharing.

• Ethics approval reference: EA4/043/25.
• The study is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice.
• Anonymised datasets and analysis scripts will be made available in public repositories.
• Metagenomic sequencing data will be deposited in an international sequence archive to ensure transparency and reproducibility.
• Results will be disseminated through peer-reviewed publications, conference presentations, and a lay summary provided to participants.