T helper 2 (Th2) polarization is a major pathological feature in allergic diseases; its etiology is not fully understood. This study aims to elucidate the adjuvant effect of the microbial product-derived small peptides in the initiation of antigen-specific Th2 polarization. In this study, a clinical survey of patients with chronic rhinosinusitis (CRS) and food allergy (FA) was carried out. The Staphylococcal enterotoxin B (SEB)-derived small peptides (Ssps) were examined in the human stool extracts. The formation of Ssp/antigen adducts was tested in a protein-protein combination assay. The bone marrow-derived dendritic cells (BMDCs) were employed to test the role of Ssp/ovalbumin (OVA) adducts in the dendritic cell (DC) maturation. A mouse model was developed to test the role of Ssp/OVA adducts in the initiation of Th2 polarization in the intestine. The results showed that 54 (18.2%) patients with FA were diagnosed among 296 patients with SEB(+) CRS; only eight (2.9%) FA patients were identified among 272 patients with SEB(-) CRS. Ssps were detected in the stool protein extracts from FA patients with SEB(+) CRS, but not in those with SEB(-) CRS. Ssp/OVA adducts induced DC maturation, speeded up DC migration, activated CD4(+) T cells in the regional lymph nodes and induced skewed Th2 polarization in the local tissue. We conclude that patients with SEB(+) CRS are prone to suffering from FA. SEB can be degraded to Ssps in the gastrointestinal tract. The Ssps can bind macromolecular antigens to form adducts to promote the antigenicity of the antigens and induction of the antigen-specific Th2 polarization and inflammation in the local tissue.