Graminan-type fructans mitigate the noxious effects in gut cells exerted by the Giardia virulence factor arginine deiminase in a fructan-specific fashion: A multi-cell approach

Graminan-type fructans (GTFs) derived from Agave plants exhibit significant health benefits, including preservation of the intestinal barrier, attenuation of proinflammatory responses, and antimicrobial effects. These properties position them as promising candidates for addressing gut health challenges. We hypothesize that these fructans may play a crucial role in countering Giardia lamblia, the protozoan responsible for giardiasis, a disease that ranges from asymptomatic colonization to chronic intestinal disorders. This pathogen employs virulence factors such as arginine deiminase (GlADI) to disrupt immune responses and compromise intestinal integrity. This study explored the protective effects of two structurally distinct graminan fructans (GTF I and GTF II) against GlADI-induced intestinal injury. We demonstrated that GlADI significantly reduces IL-8 production and disrupts mucin and tight junction gene expression in epithelial cells, contributing to intestinal barrier dysfunction. GTFs counteracted these effects, restoring IL-8 production, normalizing gene expression, and mitigating inflammatory signaling pathways. Molecular docking predicted that GTF I could inhibit GlADI-induced TLR2 activation by occupying its agonist-binding pocket, while both GTFs modulate TLR4 activation in a dose-dependent manner. These findings suggest that GTFs may represent promising candidates as natural agents for further preclinical investigation in combating Giardia infections.