Inaugural Microbiome Symposium Showcased Interdisciplinary Work Enabled by Campus Germ-Free Mouse Facility

By Martel DenHartog, Tiny Earth Chemistry Hub Manager, Handelsman Lab, Wisconsin Institute for Discovery

Last spring, over 130 scientists spanning 40+ departments convened for the inaugural UW–Madison Microbiome Symposium. Speakers highlighted research efforts enabled by the new Gnotobiotic Shared Resource (GSR), a centralized germ-free and gnotobiotic mouse research support facility established with a $1 million gift from the Wisconsin Alumni Research Foundation (WARF) through the Office of the Vice Chancellor for Research’s Microbiome Initiative.

The theme of the Microbiome Symposium was “Gut-Brain Axis,” as many attendees use the GSR to study the effect of the gut microbiome on neurological function. The gastrointestinal tract is full of viruses, bacteria, fungi, and other microbes that execute many physiological roles beyond helping us digest our food. The GSR opened to the campus community in January 2024 with a diverse cohort of studies to further uncover relationships between the gut microbiome and disease.

Scientists have found correlations between microbiome composition—the diversity of species and their functions—and disease symptoms, but determining causality is critical to discovering treatments. Introducing an intervention that modulates both host symptoms and microbiome composition strengthens the association, but it is difficult and often unethical to demonstrate causality in humans, so model organisms—like mice—provide a reliable alternative. A remarkable range of disease symptoms have been observed after transferring human microbiome samples from symptomatic people into mice lacking their own microbiome, called germ-free mice. Replacement of the mouse microbiome with human samples has produced symptoms similar to those observed in donors with obesity, Alzheimer’s disease, inflammatory bowel disease, and depression.

“The GSR is an amazing gift to the campus,” says Wisconsin Institute for Discovery director and GSR user Jo Handelsman. “Relatively few campuses have gnotobiotic facilities for general use. Usually they are located in one research group which must coordinate their own training, personnel, and maintenance of colonies. The UW–Madison GSR makes possible new avenues of microbiome investigation for our researchers.”

The shared resource mirrors other campus facilities with dedicated staff that maintain animals, equipment, and set up experiments, so every research group does not have to manage the work by themselves.

“Our university has a strong legacy in microbial and molecular biology, and the GSR helps build on that foundation by enabling deeper exploration of the interactions between environment, genes, and microbes,” says GSR manager Annie Resende. “This field holds great promise for transforming disease prevention, treatment, and diagnosis. I strongly encourage researchers to take advantage of the GSR’s resources and collaborative opportunities, as they can greatly enhance the scope, impact, and reproducibility of their work.”

Vanessa Leone, an assistant professor in the Department of Animal & Dairy Sciences, is one of eight principal investigators with current projects at the GSR. Leone investigates how the gut microbiome influences circadian rhythms that can have downstream metabolic effects on a host. Her work with the GSR involves using specific microbes, light and dark cycles, and diet to assess circadian rhythm-controlled gene expression and phenotypes. In her symposium talk, Leone expressed gratitude to WARF for assisting the GSR, especially during an uncertain time for animal research funding.

Several presenters expanded beyond the gut-brain axis theme to other microbiomes and host impacts. Chloe Schiff, graduate student in assistant professor in the department of oncology and Morgridge Institute for Research investigator Megan Spurgeon’s lab, discussed associations between the female reproductive tract microbiome and human papillomavirus (HPV) infection and disease progression. Modeling HPV with murine papillomavirus in germ-free mice allows the Spurgeon lab to better understand the virus that infects people.

Germ-free mice can also help us learn about depression, multiple sclerosis, cancer, drug addiction, and colitis from Clostridioides difficile infections, all of which investigators are studying using the GSR. The Microbiome Symposium gathered GSR users and the broader microbiome community at UW–Madison to learn from each other and nurture connections. Faculty and students across disciplines from statistics to microbiology to clinical psychology presented talks and posters accessible to the broad audience. Throughout the day, symposium attendees felt the enthusiasm about a bustling field of research at UW–Madison that will benefit from more collaboration and communication. Attendees commented on the engaged audience and the need to host events like this on where scientists from diverse fields can convene.

“Progress only happens when you have communication across different silos,” says Margaret Thairu, event organizer and scientist in the Handelsman lab. “Rarely do you see rapid progress on complex problems if you’re stuck in one department and talking to the same people all the time. UW–Madison has such a big microbiome community, and the [symposium] was a way to start providing a space where diverse researchers could come together to learn from one another and build new collaborations.”

Shai Bel, a professor at Bar-Ilan University, studies host-microbe interactions at the mucosal interface. His talk showcased work on how Candida albicans can modulate host gut cells to alter immune responses. “The symposium was fantastic,” Bel said. “I’m not a gut-brain person, but it was interesting to see connections. Even if I wasn’t [at UW] for a sabbatical, I still would have come [to the symposium].”

The event closed with an introduction to the new Precision Health Hub, a campus-wide hub hosted by the Wisconsin Institute for Discovery. The Hub is intended to foster collaborations that use AI-enabled precision solutions to address research on complex problems involving agriculture and medicine to achieve better outcomes in human health. UW–Madison is one of only a handful of universities in the United States with both a medical school and agriculture school and a powerhouse of talent in AI, which is a critical tool in precision health.

“The Hub combined with the GSR position us extremely well for research in the microbiome and precision medicine,” says Handelsman.

The Gnotobiotic Shared Resource alongside the Precision Health Hub strengthens UW–Madison’s microbiome research and precision medicine leadership. With WARF and campus support, gatherings like the Microbiome Symposium will help shape the future of these fields.