© 2018 Soler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Antimicrobials have been used in a prophylactic way to decrease the incidence of digestive disorders during the piglet post-weaning period. Nowadays, it is urgent to reduce their consumption in livestock to address the problem of antimicrobial resistance. In this study, the effect of a product on piglet microbiota has been investigated as an alternative to antimicrobials. Three groups of ten post-weaning pigs were sampled at 0, 15 and 30 days one week post-weaning; the control, antibiotic and feed additive group received a standard post-weaning diet without antibiotics or additives, the same diet as the control group but with amoxicillin and colistin sulphate and the same diet as the control group but with a feed additive (Sanacore-EN, Nutriad International N.V.), respectively. The total DNA extracted from faeces was used to amplify the 16S RNA gene for massive sequencing under manufacturer’s conditions. Sequencing data was quality filtered and analyzed using QIIME software and suitable statistical methods. In general terms, age modifies significantly the microbiota of the piglets. Thus, the oldest the animal, the highest bacterial diversity observed for the control and the feed additive groups. However, this diversity was very similar in the antibiotic group throughout the trial. Interestingly, a clear increase in abundance of Bacillus and Lactobacillus spp was detected within the feed additive group versus the antibiotic and control groups. In conclusion, the feed additive group had a positive effect in the endogenous microbiota of post-weaning pigs increasing both, the diversity of bacterial families and the abundance of lactic acid bacteria during the post-weaning period.