Biogeography of the developing pig intestine microbiome

The unprecedented rise of antimicrobial resistance (AMR) in infectious bacteria is alarming, and more deaths due to AMR than cancer are expected by the year of 2050. Livestock production is a primary consumer of antibiotics that promote AMR evolution. Although the use of antibiotics for animal growth promotion was banned in the EU in 2006, antibiotics are still administered widely for disease prevention and treatment. Swine production emerges as a key consumer of medically important antibiotics, amounting to 2.58 million kg of antibiotics and accounting for 42% of all antibiotics consumed by the animal food production industry only in the USA.

Piglets in the conventional pig industry are weaned at week 3-4 of life. The weaning transition is a stressful period for the piglets in the industry when they are separated from their mother, penned with other piglets from different sows, encounter new microbes and transit from liquid to solid food. These factors when combined with stress of weaning often leads to the development of post-weaning diarrhea (PWD) in the weaned piglets. PWD is the principal sink of antibiotic administration in industrial pig production with 85% of all antibiotics administrated being for treating PWD. In this context, it emerges that understanding the dynamic development of the piglet intestinal microbiome during PWD the first weeks of life, including the weaning transition, can provide important leads towards factors that contribute to a healthy, robust piglet intestinal microbiome. However, the understanding of microbial mechanisms and compositions explaining the microbiome assembly and function of the robust and PWD-prone, unhealthy, piglet intestinal microbiomes is still lacking.

In the past, studies have focused on characterizing prokaryotic intestinal microbiome composition of the piglets. Whereas most studies have used 16S ribosomal RNA gene-targeted approaches that provide information on microbial composition, limited information is available regarding the development of microbial functionality, for which metagenome approaches are needed. Moreover, studies mostly focused on prokaryotes, whereas little attention has been given to the role of microeukaryotes and viruses in piglet health and PWD during weaning. Also, studies have mostly focused on faecal and few selected intestinal content samples, whereas the dynamic development of mucosa-associated microbiomes along the intestinal tract is less well understood. Altogether, we hypothesize that integrated analysis of the dynamic development of all components of the microbiome at high spatio-temporal resolution can provide leads for novel diagnostic tools for healthy microbiome development and deviations thereof in PWD. Furthermore, improved understanding of these developmental processes can also provide new insight towards microbiome management for the prevention PWD.

To sum up the project will aim to respond to questions of:

• How does microbiome composition and function from different intestinal regions and tissues develop in early life?

• Can we identify differences in this spatio-temporal development between healthy and PWD piglets?

• What are the developmental trajectories of microbial communities from different intestinal organs and tissues during the development of piglets in industry?

Techniques

We would employ qPCR for absolute quantification of microbes, amplicon sequencing for genus-species level taxonomic classification and shotgun metagenomics sequencing for cross-kingdom, strain-level resolution analysis of microbiome composition and function.