Pectins mitigate Candidalysin-induced gut barrier disruption and inflammation in vitro in a degree of methyl-esterification-dependent manner

Pectin, a dietary fiber, exhibits anti-inflammatory properties influenced by its degree of methyl-esterification (DM). Inflammatory bowel disease (IBD) is characterized by chronic inflammation due to a compromised epithelial barrier, dysregulated microbiota, and an overactive immune response. Beyond bacterial dysbiosis, recent research emphasizes the gut mycobiota, particularly Candida albicans, in IBD progression. C. albicans is frequently elevated in IBD patients and secretes candidalysin (CaLysin), a cytolytic toxin that disrupts epithelial barrier integrity. This study evaluates the protective effects of lemon-derived pectins with low (DM18) and high (DM88) DM against CaLysin-induced epithelial-stress in vitro. T84 cell monolayers were pre-treated with pectins prior to CaLysin challenge. CaLysin impaired barrier function, increased lactate dehydrogenase (LDH) release, and pro-inflammatory cytokines (e.g., IL-8, IL-33), while downregulating tight junction proteins (Claudin-1, Occludin) and tissue repair markers such as Retinaldehyde dehydrogenase 1 (ALDH1A1) and Amphiregulin (AREG). Both pectins mitigated these effects, preserving barrier integrity, reducing LDH release, and cytokine expression (e.g., IL-8, IL-13, IL-18, CCL20). Pectins also upregulated tight junction proteins (Claudin-1, Occludin, Zonula Occludens-1) at mRNA and protein levels in a DM-dependent manner and enhanced tissue repair genes. These findings highlight the potential of pectins, particularly those with low-DM (DM18), in protecting against CaLysin-induced gut epithelial damage.