Supplementation of the antimicrobial peptide Ctx(Ile21)-Ha microcapsules improves fecal recovery dynamics in suckling piglets without altering pre-weaning growth

Antibiotics use has contributed to antimicrobial resistance, reinforcing the need for safe alternatives for piglet health. Antimicrobial peptides are promising candidates, but gastrointestinal instability limits oral use. This study evaluated hydroxypropyl methylcellulose phthalate (HPMCP) enteric-coated microcapsules containing the antimicrobial peptide Ctx(Ile 21 )-Ha as a nutritional intervention for suckling piglets. Peptide was synthesized by solid-phase peptide synthesis and properly purified and characterized, confirming high purity and identity. Microcapsules were produced by ionotropic gelation and coated with HPMCP, achieving high encapsulation yields (84.7–87.5%) and predictable peptide loading. In a commercial farm, 136 piglets were allocated within litters to control or two prophylactic dosing regimens administered on days 1, 2, 5, 10, and 13 of age. Pre-weaning average daily gain did not differ among treatments. Piglets that developed diarrhea (n = 35) entered a therapeutic phase comparing injectable antibiotic control with two oral peptide doses. Time to diarrhea onset was similar across groups. Time-to-event analyses indicated rapid cessation in all treatments; the lower peptide dose showed a numerically higher hazard of cessation versus control, although not statistically supported. Repeated fecal scores analyzed with a Bayesian ordinal mixed model indicated lower fecal scores in the lower-dose peptide group compared with control, with higher predicted probability of normal feces on day 1 after onset. These results suggest that enteric-coated microencapsulated Ctx(Ile 21 )-Ha may support fecal recovery without impairing growth, although therapeutic findings should be interpreted considering the field-based design and absence of individual bacteriological confirmation before treatment.