| Little is known about the gut mycobiome in health or disease. Recently, we discovered a novel Paneth cell anti-microbial peptide (nAMP), that is also a gut hormone classically recognized for its role in satiety. nAMP is abundantly expressed and packaged in discrete dense core granules of Paneth cells (PC), secreted luminally, and bears remarkable similarity to a class of AMPs typified by the amphibian magainin-2 peptide. Unlike magainin-2, nAMP has limited anti-bacterial activity and specifically targets the virulent (hyphal), but not commensal yeast forms, of gut fungi like Candida albicans. Thus, nAMP could play a key role in maintaining fungal commensalism in the healthy gut. Interestingly, Paneth cell dysfunction has been reported in patients with ileal Crohn’s disease (iCD), which has been linked to several genetic variants, immune and inflammatory stress, and other factors. Altogether, these factors can promote fungal virulence that contributes to the pathogenesis of iCD and may explain the observed increases in fungal load and positive anti-Saccharomyces cerevisiae serum antibodies (or ASCA) that are often associated with risk and severity of iCD. Further characterization of nAMP could lead to a useful predictive biomarker to identify iCD patients mostly likely to benefit from measures to restore fungal commensalism. |
