NLRP12 encodes the nucleotide-binding leucine-rich repeat-containing receptor 12 protein and has been linked to familial cold autoinflammatory syndrome 2 (FCAS2). Previous studies have reported that NLRP12 protein can dampen inflammatory responses in DSS-induced mice colitis. To date, only four alterations in the NLRP12 gene have been associated with Crohn’s disease (CD). Here, we reported a novel heterozygous NLRP12 frameshift mutation (c.2188dupG, p.Val730Glyfs41) identified by whole-exome sequencing in the proband with CD. The Sanger sequencing confirmed that his sister and father also carried this NLRP12 mutation, which cosegregated well with the CD phenotype. In silico analysis predicted this mutation to be disease-causing. Patients heterozygous for this mutation exhibited decreased NLRP12 protein levels in the peripheral blood and colon. Functional assays showed that mutant NLRP12 plasmid-transfected HEK293T cells exhibited significantly lower NLRP12 mRNA and protein levels than wild-type plasmid-transfected cells. The nonsense-mediated decay inhibitor NMDI14 significantly increased NLRP12 mRNA and protein levels in mutant plasmid-transfected cells. Overall, our results demonstrated that this heterozygous NLRP12 mutation (c.2188dupG) resulted in decreased NLRP12 expression, which might contribute to the mechanism underlying CD.

Inflammatory bowel disease (IBD) is associated with microbial dysbiosis, yet subtype-specific alterations in the tongue-coating microbiome remain insufficiently characterized. In this cross-sectional study, tongue-coating samples from 158 participants (94 healthy controls [HC], 19 ulcerative colitis [UC] patients, and 45 Crohn’s disease [CD] patients) were analyzed by 16S rRNA gene amplicon sequencing. We compared alpha and beta diversity, taxonomic composition, differential taxa, exploratory random-forest feature rankings, and SPIEC-EASI co-occurrence networks. Species richness did not differ significantly among groups, whereas Shannon and Simpson indices were lower in UC than in HC and CD. Bray–Curtis and Jaccard ordinations showed significant but partially overlapping community differences among the three groups. UC was characterized by enrichment of Proteobacteria, Neisseria, and Porphyromonass (p < 0.001), whereas CD showed higher relative abundances of Prevotella, Veillonella, Leptotrichia, and TM7x. Random forest and LEfSe analyses yielded concordant candidate discriminative taxa, but no independent validation cohort was available. Network analysis suggested group-specific co-occurrence patterns, with results interpreted as statistical associations rather than direct microbial interactions. These findings support the presence of subtype-associated tongue-coating dysbiosis in IBD and identify candidate taxa for future validation.