Undercover Operative: Environmental Microbiologist Infiltrates the World of Human Microbiome Research

BTI Researcher Christopher Staley uses an ecology framework to tackle the human microbiome and its intricate secrets.
April 24, 2023

Can your poop cure disease? Sounds ridiculous until you hear stories from patients helped by a fecal microbiota transplant (FMT). BTI Researcher Christopher Staley left the banks of the Mississippi River and dove head first into the diverse ecosystem living inside our digestive tract: the microbiome. But how did he get there?

During his undergraduate and graduate studies, Staley met Michael Sadowsky, a distinguished microbiologist and then director of the University of Minnesota BioTechnology Institute. After mingling at several research conferences, Sadowsky offered Staley a job studying water quality at pollution sites along the Mississippi River. Staley’s role was to isolate and analyze DNA sequences from microorganisms living in the water and sediment.

With no expertise in mathematical modeling for biological systems or computational biology, Staley was concerned about his new position, but Sadowsky reassured him he was a good fit. Staley offered a new perspective to the team of bioinformatic scientists that would process the data. He understood the connections to the larger ecosystem.

“I learned how to speak both languages,” recounts Staley. “And we found eight stories hidden in their data which were all eventually published.”

Much like the waters of the Mississippi, the digestive tract harbors countless microbial communities. When Sadowsky introduced Staley to fellow BTI researcher Alexander Khoruts’ work on the microbiome, a natural partnership emerged. 

Khoruts and Sadowsky were instrumental in developing the modern use of microbiota transplant therapeutics (MTT), though the practice dates to fourth-century China when people suffering from severe diarrhea were treated using a soup of dried fecal matter (yes, you read that correctly) to restore the balance of bacteria in the gut. Khoruts and Sadowsky sought a modern approach to help patients suffering from stubborn Clostridium difficile infections that cause severe stomach cramping, diarrhea, and abdominal pain. But faced with the complexity of the microbiome, Khoruts and his team had many unanswered questions.

After analyzing their dataset, Staley recognized that environmental science offered some solutions. “The tools and techniques we used studying the river are the same for fecal samples. They thought their questions were hard, but I saw them through a different lens.” He recalls the collaboration as a success because they respected each other’s expertise, which presented complementary analytical perspectives. 

After dabbling in clinical research, Staley’s curiosity was piqued, so he pursued a position in the Department of Surgery at the University of Minnesota. 

Navigating the transition from environmental to clinical research was challenging. Staley built on his background in ecology to explore links between the microbiome and human disease while working with University of Minnesota physician Armin Rashidi, who studies the effects of leukemia treatment on the microbiome. 

Knowing that antibiotics can wreak havoc on the microbial balance in the body, Rashidi sought to understand the potential impact on his patients. Working together, Rashidi and Staley determined that antibiotics—while effective in treating harmful infections—also destroyed the helpful bacteria that keep our bodies healthy. This paradox proved fundamental to understanding the connection between the microbiome and disease and how microbial communities interact to support and undermine human health.

The microbiome has been linked to obesity, colorectal cancer, and almost every illness researchers could find. And while microbiome research has blossomed over the last decade, Staley estimates about 15 percent of studies pay adequate attention to microbial community function, and even fewer explore a critical component of bacterial communication: quorum sensing. Staley’s new focus is on disrupting the signaling molecules bacteria use to communicate with quorum quenching techniques, in collaboration with BTI investigator Mikael Elias, which prevent synchronized behavior in microbial communities.

“Of course, they’re talking in there,” says Staley. “Did you think the bacteria were just sitting there, ignoring each other? There are trillions of them!”

In preliminary testing in mice, Staley found evidence that quorum sensing could play a significant role in the gut-body connection. When fed a Western diet, quorum-quenching mice were more resistant to diet-induced obesity than mice in the control group. While only a preliminary trial, Staley is enthusiastic about digging into the mechanics of bacterial communication and its impact on the human body. 

Does he miss the Mississippi and his work in environmental science? Staley’s lab is a short walk from the mighty river, and as he points out: “First, I was looking for the effects of pollutants on a body of water, and now I’m analyzing fecal matter for how bacteria impact the body … it’s almost the same!” — Emerson Mehring