Infecção por Escherichia coli não diarreiogênica altera os aspectos morfofuncionais em modelo murino de desnutrição

Abstract

Childhood malnutrition remains a major challenge in low- and middle-income countries, compromising growth, immunity, and the intestinal barrier. Although diarrheagenic *E. coli* pathotypes have been extensively studied in this context, the intestinal effects of uropathogenic strains (UPEC) remain poorly explored. This study investigated, in a murine model, the effects of UPEC infection combined with the MAL-ED multi-deficient diet on intestinal epithelial structure and function, correlating the findings with the strain's whole- genome sequencing. C57BL/6 mice were assigned to six experimental groups and monitored for 21 days, with assessments of clinical parameters, body composition, intestinal function (lactulose/mannitol test), and small intestine morphometry. UPEC infection significantly reduced growth, fat-free mass, and body water compartments, with more pronounced effects in malnourished animals (p<0.05). Alterations in villus and crypt areas and increased

intestinal permeability were observed in infected animals, particularly those on the multi- deficient diet (p=0.0023). Genomic analysis revealed virulence genes and toxins associated with intestinal barrier damage. The combination of malnutrition and UPEC infection exacerbated the impairment of epithelial integrity and growth, demonstrating that extra- intestinal strains can negatively modulate intestinal pathophysiology and highlighting the model's potential to inform nutritional and therapeutic interventions for vulnerable pediatric populations