Early Inoculation of a Multi-Species Probiotic in Piglets–Impacts on the Gut Microbiome and Immune Responses

Intestinal diseases in nursery pigs harm health and performance and drive antimicrobial resistance. This study evaluated whether early probiotic inoculation helps piglets to cope with weaning-related gut challenges. The probiotic, containing <i>Lacticaseibacillus rhamnosus</i>, <i>Enterococcus lactis</i>, <i>Bifidobacterium longum</i> subsp. <i>infantis</i>, and <i>Bifidobacterium breve</i>, was given orally to newborn piglets daily until day 4 and then every other day until weaning at day 28 (at 4 × 10⁹ CFU/dose). The control piglets received a placebo. The results showed that the probiotic pigs had reduced fecal alpha-diversity on day 7 but greater Shannon diversity on day 28 (feces) and day 23 (intestinal contents) compared to those of the control pigs. Beta-diversity analysis showed microbial differences between the groups on day 35. Most zOTUs (zero-radius operational taxonomic units) found to significantly differentiate the two treatment groups were found pre weaning. <i>Bifidobacterium breve</i>, <i>Ligilactobacillus salivarius</i>, as well as <i>Clostridium ramosum</i> were significantly more abundant in the feces of the probiotic pigs more than once. The probiotic pigs had higher expression levels of mucin 2 (MUC2); solute carrier family 5, member 8 (SLC5A8); and interleukin 8 (IL-8) post weaning. In the early post-weaning period, the probiotic pigs had less diarrhea as well as lower cadaverine levels in digesta than the control pigs. In conclusion, early probiotic inoculation may induce lasting immunomodulation via microbial antigen changes, enhancing resilience during challenges, like weaning. Notably, the effects persisted beyond weaning and probiotic cessation.