Lectin-Seq: a method to profile lectin-microbe interactions in native communities

Soluble human lectins are critical components of innate immunity. Genetic models suggest lectins influence host-resident microbiota, but their specificity for commensal and mutualist species is understudied. Elucidating lectins’ roles in regulating microbiota requires an understanding of which microbial species they bind within native communities. To profile human lectin recognition, we developed Lectin-Seq. We apply Lectin-Seq to human fecal microbiota using the soluble mannose-binding lectin (MBL) and intelectin-1 (hItln1). The microbial interactomes of MBL and hItln1 differ in composition and diversity. MBL binding is highly selective for a small subset of species commonly associated with humans. In contrast, hItln1’s interaction profile encompasses a broad range of lower-abundance species. Our data uncover stark diffearences in the commensal recognition properties of human lectins. One-Sentence Summary Soluble human lectins bind distinct bacterial species in fecal microbiota.