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We evaluated the potential of multi-strain probiotic (Bifidobacterium longum subsp. infantis CECT 7210 and Lactobacillus rhamnosus HN001) with or without galacto-oligosaccharides against enterotoxigenic Escherichia coli (ETEC) F4 infection in post-weaning pigs. Ninety-six piglets were distributed into 32 pens assigned to five treatments one non-challenged (CTR+) and four challenged control diet (CTR-), with probiotics (3 × 1010 CFU/kg body weight each, PRO), prebiotic (5%, PRE), or their combination (SYN). After 1 week, animals were