Iron will, microbial thrill: A dissertation that digs deep
By Shaila Ann Sigsgaard
What happens when you tweak iron levels in a pig’s diet? You don’t just change growth rates -you shift microbial ecosystems, alter metabolic pathways, and potentially influence pathogen virulence. That’s the premise behind Shya Navazesh’s PhD dissertation, a four-chapter investigation into the complex relationship between dietary iron and gut health in swine. Her work spans cell culture, in vivo studies, metagenomics, and whole genome sequencing, offering a multi-layered view of how iron interacts with intestinal biology.
“Iron is a key nutrient—not just for the host, but for the microbes,” Navazesh explains. “We wanted to understand how dietary iron affects gut health at the cellular, microbial, and genomic levels.”
Navazesh began her research in Dr. Peng Ji’s lab at the University of Illinois in 2020. The lab’s core focus is iron metabolism and intestinal health, and her first project centered on IPEGJ2 cells—intestinal epithelial cells used to model enterocyte behavior. “I came in with a background in cell culture,” she says. “We were particularly interested in how iron deficiency or supplementation could influence enterocyte metabolism.”
Her first research chapter revealed that both iron deficiency and acute iron supplementation modulate cell metabolism. “We saw changes in cellular iron regulation, lipid metabolism, and mitochondrial energy pathways,” she explains. These findings laid the groundwork for her subsequent vivo studies, which aimed to translate cellular insights into whole-animal outcomes.
The second and third chapters of her dissertation involved a controlled feeding study with 50 post-weaning pigs. The animals were assigned to five dietary treatments: control, low iron, high iron, zinc oxide, and copper sulfate. “We wanted to see how dietary iron influences growth performance and gut microbiota,” Navazesh says. “Especially since bacteria also rely on iron—and increasing it could raise the risk of enteric infections.”
The inclusion of zinc oxide and copper sulfate was strategic. “These are currently used as alternatives to antibiotics in the U.S.,” she notes. “But the EU has already banned zinc oxide for environmental reasons. So, we wanted to compare our iron treatments with what’s currently used in industry—and explore alternatives to those alternatives.”
After 24 days of their respective diets, the piglets showed modest shifts in microbiome composition. “Increasing iron and copper led to marginal changes,” Navazesh says. “But low iron diets showed increases in bacteria associated with pathogens—like Escherichia, the genus that includes ETEC, a major pig pathogen.”
Although the study didn’t induce full-blown infection, the microbial signals were clear. “We saw trends that suggest low iron may create conditions favorable to pathogenic bacteria,” she explains. “That’s something we need to investigate further in future pathogen challenge studies.”
PIG-PARADIGM: Collaboration
One of the most transformative elements of Navazesh’s PhD experience was her involvement in PIG-PARADIGM, an international research collaboration focused on pig health and nutrition. “The collaboration aspect of Pig Paradigm is probably one of the most valuable takeaways from the project,” she says.
Her home lab didn’t specialize in microbiology or bioinformatics, two areas critical to her research. “Through Pig Paradigm, I met people who asked the right questions, challenged my work, and helped me grow,” she says. “It’s rare to have that kind of support during a PhD. It allowed me to learn more than what my lab could offer—and that’s been phenomenal.”
The final chapter of her dissertation leveraged these collaborative strengths. Using metagenomics and whole genome sequencing, Navazesh analyzed antimicrobial resistance genes and functional profiles in fecal samples and E. coli isolates. “We sequenced samples from day 1, day 12, and day 24 to track changes over time,” she explains.
The results were surprising. “Iron didn’t have much impact on resistance genes,” she says. “But zinc oxide showed the largest changes—altering carbohydrate metabolism and folate and arginine pathways. That was unexpected, and it gives us new angles to explore.”
More concerning was the E. coli isolates from the low iron group. “We saw elevated virulence gene expression,” Navazesh says. “Not a huge shift in overall profile, but enough to suggest that iron modulation could influence pathogen behavior. Especially at day 12, we saw signals that warrant further study.”
Challenges, insights, and what comes next
Despite the technical complexity of her work, Navazesh found the writing process to be the most challenging part of her PhD. “Interpreting results and making sure the statistics align with your claims—it’s tough,” she admits. “The bioinformatics and data analysis were challenging but fun. Writing was just me, sitting alone, trying to make sense of everything.”
Still, she views the experience as a valuable learning opportunity. “There were so much help and collaboration in other aspects of the project,” she says. “But writing felt more solitary. Less enjoyable, for sure.”
Looking ahead, Navazesh sees clear directions for future research. “We need a pathogen challenge study to really understand how ETEC responds to iron,” she says. “And now that we’ve seen how zinc oxide affects microbial function, we have new targets for potential therapies.”
Her dissertation doesn’t just answer questions—it opens new ones. And thanks to the support of PIG-PARADIGM, she’s equipped to keep asking them.
About Shya Navazesh
Shya Navazesh is a PhD candidate in the University of California, Davis. Her research focuses on iron metabolism, intestinal health, and microbial dynamics in swine. She specializes in cell culture, in vivo experimentation, and bioinformatics, with a strong emphasis on metagenomics and pathogen profiling. Through her involvement in the PIG-PARADIGM collaboration, she has contributed to cutting-edge research on dietary modulation and microbial ecology and is passionate about advancing animal health through interdisciplinary science.
