# Early antimicrobial regimen shapes gut microbiota and health trajectories in pigs: a longitudinal study from weaning to finishing

## TL;DR

This study shows how different antimicrobial use in pigs affects their gut microbes, immune health, and antibiotic resistance over time.

## Contribution

The study reveals how early antimicrobial regimens influence gut microbiota, immune parameters, and antimicrobial resistance genes in pigs from weaning to slaughter.

## Key findings

- SPC1 pigs showed higher antimicrobial resistance gene enrichment after treatment with lincomycin and spectinomycin.
- SPC2 pigs had persistent resistance gene enrichment despite limited antimicrobial use, linked to mobile genetic elements.
- Microbial diversity and immune markers varied significantly between the two rearing conditions over time.

## Abstract

This study investigated the longitudinal evolution of the gut microbiota, immune parameters, and antimicrobial resistance genes (ARGs) in pigs from pre-weaning to slaughter under two contrasting rearing conditions differing in antimicrobial use. At day (d) twenty-one postnatal, 96 piglets from 22 litters were assigned to SPC1 (Swine Production Chain 1) or SPC2 (Swine Production Chain 2) and maintained on the same stage specific diets until slaughter. Faecal and blood samples were collected at d21 (T1, pre-weaning), d42 (T2), d80 (T3), d98 (T4), and d278 (T5). Analyses included 16 S rRNA gene and shotgun faecal microbiome profiling (200 samples; 22 SPC1 and 18 SPC2 pigs), faecal polyamines, blood cell counts, immunoglobulins, oxidative stress markers, and ARGs profiling from metagenome-assembled genomes. From T1 to T2, all SPC1 pigs received group-level antimicrobials in water, whereas only seven SPC2 pigs were treated individually. At T2, SPC2 showed lower mean corpuscular haemoglobin concentration and monocytes but higher red blood cells, haemoglobin, and haematocrit (P < 0.05). At T3, SPC2 had higher red and white blood cells, basophils, and neutrophils but lower haemoglobin, haematocrit, and monocytes (P < 0.05). Gut microbial alpha diversity was significantly influenced by the Time × SPC interaction (P < 0.001). Key species differentiating SPC1 and SPC2 included Megasphaera elsdenii, Lactobacillus johnsonii, and L. reuteri (SPC2) versus Prevotellaceae NK3B31 and Rikenellaceae RC9 (SPC1) (LDA > 4, P < 0.01). Pathways for drug and xenobiotic metabolism were enriched in SPC1 at T3 (log2FC = 1.5, P adj. = 0.04). Dynamic Time Warping clustering revealed distinct microbial profiles in pigs with similar lymphocyte or neutrophil trajectories (R² = 0.002, P = 0.04; R² = 0.002, P < 0.01). ARG analysis revealed contrasting resistome patterns. In SPC1, metaphylactic treatment with lincomycin and spectinomycin led to transient enrichment of aminoglycoside resistance genes at T2 (log2FC = 2.1–2.4, P adj. < 0.05) and additional glycopeptide and multidrug genes at T3 (log2FC = 1.8–2.6, P adj. < 0.05), with no enrichments by T5. In SPC2, despite limited antimicrobial use, early and persistent enrichment was observed for MLS, tetracycline, aminoglycoside, beta-lactam, and multidrug resistance genes (log2FC = 1.7–3.2, P adj. < 0.05), many associated with mobile genetic elements. In conclusion, rearing practices, particularly antimicrobial protocols, shaped gut microbiota composition, immune responses, and the resistome from suckling to finishing.

The online version contains supplementary material available at 10.1186/s42523-025-00477-x.