Animal only
This mouse study investigated whether potassium-competitive acid blockers (P-CABs), sometimes empirically used for eosinophilic gastrointestinal diseases, might worsen eosinophilic enteritis (EoN) under psychological stress conditions. Researchers established an EoN model in BALB/c mice using ovalbumin sensitization and challenge, then exposed animals to water avoidance stress (WAS) or sham stress, with or without P-CAB administration. Compared to the WAS-only group, WAS combined with P-CAB significantly worsened multiple disease markers, including diarrhea incidence, villus/crypt ratio, eosinophil and mast cell counts, Th2 cytokine expression (mRNA and protein), OVA-specific IgE levels, and ileal permeability measured via Ussing chamber. The study further found that larazotide acetate, a zonulin inhibitor targeting gut tight junctions, reduced ileal inflammation and permeability in WAS + P-CAB-treated EoN mice, suggesting a permeability-mediated mechanism. Key limitations include exclusive use of a mouse model, which may not fully replicate human eosinophilic gastrointestinal disease, and the artificial nature of the stress and sensitization protocols. These findings raise important cautions about P-CAB use in patients with EoN who may be under psychological stress, though human clinical evidence is still lacking.
Digestion · Apr 2026DOI ↗ Animal only
This preclinical study developed a dual-crosslinked injectable hydrogel (HSMP-LA) designed to mimic natural gut mucus for treating colitis. The hydrogel combined thiol/maleimide-modified hyaluronic acid with two active agents: antimicrobial ε-polylysine (ε-PL) and larazotide acetate (LA), a tight junction–regulating peptide. In laboratory (in vitro) experiments using LPS-injured Caco-2 intestinal cells, sustained release of LA was reported to selectively inhibit zonulin-mediated tight junction disruption by targeting the MLCK/p-MLC signaling pathway, thereby restoring epithelial barrier integrity. The hydrogel also demonstrated broad-spectrum antimicrobial activity and strong mucoadhesive properties with prolonged retention. In a dextran sodium sulfate (DSS)-induced mouse model of colitis, HSMP-LA significantly reduced disease activity indices, suppressed pro-inflammatory cytokines, upregulated anti-inflammatory IL-10, repaired tight junction proteins (ZO-1, occludin, claudin-5), restored mucus production (MUC2), and rebalanced gut microbiota composition. The study's primary limitations are that all findings are confined to cell culture and animal models, with no human data reported. The dual-action strategy—simultaneously targeting barrier dysfunction and microbial imbalance—represents the authors' proposed innovation, though clinical translation remains undemonstrated.
Journal of controlled release : official journal of the Controlled Release Society · Sep 2025DOI ↗ Animal only
This rat study investigated whether larazotide acetate (LA), a tight junction regulator that blocks zonulin receptors in the intestinal epithelium, could reduce intestinal barrier dysfunction and bacterial translocation in an experimentally induced acute pancreatitis (AP) model. Thirty-two male Sprague-Dawley rats were divided into four groups (control, larazotide-only, AP, and AP + larazotide). AP was induced via intraperitoneal L-Arginine injections, and LA was administered orally for seven days prior to AP induction. Intestinal permeability was assessed using FITC-Dextran, bacterial translocation was evaluated by culturing samples from liver, mesentery, and spleen, and intestinal histopathology including zonulin-1 (ZO-1) immunoreactivity was analyzed. The study found that, compared to the AP-only group, the AP + LA group showed significantly reduced intestinal damage scores, lower serum FITC-Dextran levels, decreased ZO-1 immunoreactivity, and a lower frequency of bacterial translocation. Key limitations include the exclusive use of an animal model, a small sample size, a single AP-induction method (L-Arginine), and a prophylactic rather than therapeutic administration design, which may limit clinical translatability.
Digestive diseases and sciences · Mar 2024DOI ↗