Fosfomycin mitigated apoptosis while increased mucin secretion in swine intestinal explants challenged by Lawsonia intracellularis

Lesions induced by the obligate intracellular bacterium Lawsonia intracellularis, the etiological agent of porcine proliferative enteropathy, are characterized by crypt hyperplasia in the intestinal epithelium with minimal inflammatory infiltration. An increased population of immature enterocytes at the expense of reduced goblet cells suggests that dysregulated apoptosis may be crucial in the pathogenesis of L. intracellularis. Fosfomycin, a widely employed antibiotic in swine production, has also exhibited non-microbicidal effects, encompassing immunomodulation, augmentation of phagocytosis, and the promotion of cell survival. In this study, we assessed the immunomodulatory impact of fosfomycin on intestinal epithelial homeostasis using porcine intestinal explants challenged with L. intracellularis. Our findings reveal that L. intracellularis elicited significant nuclear alterations, increased apoptotic indices, and prompted extensive mucin secretion in the intestinal explants. When fosfomycin was added to L. intracellularis- challenged intestinal explants, it mitigated the degree of apoptosis but also induced an inflammatory response. Consequently, treatment with fosfomycin in the context of L. intracellularis challenge appears to initiate an early mucosal response, maintaining cell viability, preserving the mucin barrier, and fostering inflammatory recruitment. Fil: Pérez, Denisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina Fil: Fodor, Cristina. University of Calgary; Canadá