Project Number: 8042-31440-002-000-D
Project Type: In-House Appropriated
Start Date: Jul 24, 2022
End Date: Jul 23, 2027
Objective 1. Determine interactions occurring across kingdoms (bacterial, fungal, porcine) at the microbe-lumen interface of the gut. Sub-objective 1A: Identify quorum sensing molecules used by K. slooffiae. Sub-objective 1B: Use microbiome datasets to determine interactions occurring between taxa, identify keystone taxa, and identify molecules present in EV that may be mediating these interactions. Sub-objective 1C. Identify the mechanism of action for the QSM identified in the pig intestinal tract for biological effects on the IPEC-J2 jejunal cell line. Objective 2. Identify alternatives to antibiotics through bioinformatics-based approaches, including the microbiome, metagenome, and metatranscriptome approaches, and examine their effects on the innate immune response at the gut mucosa. Sub-objective 2A: Use ML to model microbiome data to identify species that are critical determinants of good and poor growth. Sub-objective 2B: Identify potential probiotic candidates through in vivo testing of hypotheses generated during network analyses in Objectives 1B and 2A. Objective 3. Identify the role of Kazachstania slooffiae, a porcine fungal commensal, in pig performance through in vivo and in vitro studies. Sub-objective 3A: IPEC-J2 cell line challenges with live or heat killed K. slooffiae to analyze innate immune response. Sub-objective 3B: Dose-response feeding trial of K. slooffiae to post-weaning pigs. Objective 4. Identify mechanisms of action of antibiotics and of their alternatives in promoting the growth and well-being of swine by examining metagenomes and metatranscriptomes in the swine GI tract. Sub-objective 4A: Feeding trial in pigs with in-feed antibiotics. Sub-objective 4B. Dietary probiotic effects on pre- and post-weaning growth and intestinal physiology. Sub-objective 4C. Evaluate Clostridium scindens to promote the preweaning growth of pigs. Sub-objective 4D: Use ML in conjunction with metagenomic data to identify species, genes, and pathways that are critical in microbiome response to low dose antibiotics.
This project aims to determine the mechanisms behind antibiotic-induced animal growth and identify potential alternative growth promotants in swine during the weaning transition. Weaning is a critical point in piglet development marked by elevated stress and a predisposition to infections by opportunistic pathogens. These infections result in financial loss to farmers and producers due to increased mortality rates, reduced growth performance, increased feed costs, and veterinary expenses. Previously, in-feed antibiotics were utilized to prevent infections with the added benefit of antibiotic-associated weight gain, but the ban of in-feed antibiotics for agricultural animals presents a new challenge. Identification of alternative interventions and improved production strategies are needed to increase animal growth and disease resilience, but the mechanism behind antibiotic-induced growth remains unknown. We propose to utilize a combinatorial approach of in vitro, in vivo, and bioinformatics-based methods to identify mechanisms behind antibiotic-induced growth performance in piglets and physiological pathways altered by in-feed antibiotics to allow targeted identification of alternatives to antibiotics (ATA). These data will be utilized to optimize machine learning (ML) methods to identify microbiome members and molecules of interest in growth performance. These findings will be used to clarify the mechanism of growth promotion, thus permitting educated targeting of species and physiological pathways as ATA. Further, the microbial interactions in the gut of piglets will be analyzed to determine mechanisms behind cross-kingdom signaling that alter piglet health and growth during the weaning transition. This project will enhance the scientific understanding of the microbial network in the porcine gut and its role in growth promotion. This proposal will also determine physiological pathways altered by in-feed antibiotics to allow targeted identification of ATA in swine during the weaning transition. Farmers and producers will directly benefit from implementing validated alternate production management practices that will directly impact swine growth efficiency.