Harnessing the nasal microbiome to reduce livestock-associated Staphylococcus aureus in pigs
Authors:   , Vlasblom Abel Adriaan 
Published: January 2025

The presence of livestock-associated Staphylococcus aureus (LA-SA), including its methicillin-resistant variants (LA-MRSA), in pig farming presents a zoonotic risk to public health. This thesis aimed to identify bacterial species negatively associated with LA-SA within the nasal microbiome of healthy pigs and explore their potential to reduce LA-SA colonization through competitive exclusion. The porcine nasal microbiome, an underexplored niche, was analyzed to identify promising probiotic candidates, with Lactococcus lactis emerging as a potential intervention to reduce S. aureus colonization.
To this end chapters 2 and 3 describe the development and composition of the piglet nasal microbiome, and suggest it is influenced by factors such as time and farm-specific conditions. The microbial community stabilizes post-weaning, dominated by core genera like Moraxella and Streptococcus. Microbial diversity is likely shaped by maternal microbial transfer, gut-associated microbes introduced after birth, host factors, and farm management practices. Co-abundance groups (CAGs) were identified, revealing complex microbial interactions that may suppress pathogens. However, farm-specific variables complicate identifying microbial relationships. These findings support microbiome-based strategies, optionally while focusing on specific CAGs, to reduce respiratory infections.
Microbiome analysis and quantitative S. aureus PCR estimates identified 54 bacterial species negatively associated with S. aureus. From these, suitable isolates were literature screened and isolated using MALDI-TOF, 16S rDNA sequencing, phenotyping, whole genome sequencing, and in vitro competition assays. This effort identified three L. lactis strains as candidates with probiotic potential. L. lactis is recognized as safe (GRAS/QPS status) and literature and in vitro tests have shown its potential to inhibit S. aureus via nutrient competition or acidification. However, field applications in piglets across six European farms failed to reduce LA-SA colonization, likely due to poor colonization of the nasal cavity by L. lactis. Environmental factors, microbial competition, timing of administration, and inefficient delivery methods were identified as potential challenges. Proposed solutions, including repeated dosing or environmental dispersal, require further exploration.
A small-scale safety assessment (Chapter 5) revealed immunomodulatory effects of L. lactis, including reduced IL1B and increased pBD2 and TLR9 expression in nasal tissues, suggesting potential benefits in reducing MRSA carriage through immunomodulation. Further studies are needed to confirm these effects.
Additionally, electrostatic dust collectors (EDCs) were evaluated for monitoring airborne S. aureus transmission. EDCs proved cost-effective and reliable for long-term pathogen surveillance, reflecting airborne contamination levels without particle size bias. Their utility supports predictive models for pathogen spread and intervention strategies.
In conclusion, this thesis underscores the intricate dynamics of the piglet nasal microbiome and its potential for pathogen exclusion through probiotics like Lactococcus lactis. Despite challenges in probiotic delivery, findings highlight the promise of microbiome-based interventions to combat antimicrobial resistance. EDCs also offer practical tools for pathogen monitoring, contributing to improved livestock health and reduced reliance on antimicrobials. These insights pave the way for future research on microbiome-based strategies in livestock and public health.