Scientists have identified a new way to distinguish healthy guts from diseased ones and track how some illnesses progress by measuring how gut bacteria interact with one another.
According to a study published in Science, a collaboration between scientists at Rutgers University, Universidad de Granada in Spain and Princeton University found that healthy and diseased gut microbiomes behave like two distinct ecological states, driven not by individual microbes but by how entire bacterial communities compete and cooperate.
"Instead of asking which bacteria are there, we started asking how they are related to other bacteria," said Juan Bonachela , an associate professor with the Department of Ecology, Evolution and Natural Resources at the Rutgers School of Environmental and Biological Sciences and a senior author of the study. "That change in perspective allowed us to see health and disease as two fundamentally different states of the gut microbiome."
To measure how bacterial communities shift between health and disease, the team developed a new metric called the Ecological Network Balance Index, or ENBI, which captures whether microbial communities are dominated by competitive or cooperative interactions.
Applied to existing data, the ENBI consistently separated healthy individuals from patients across multiple diseases. In colorectal cancer, the index rose as the disease progressed.
"Our new measure could capture this shift by, for example, using stool samples, distinguishing healthy people from diseased people," said Maria Gloria Dominguez-Bello , the Henry Rutgers Professor of Microbiome and Health in the Department of Biochemistry and Microbiology at the School of Environmental and Biological Sciences and an author of the study.
Dominguez-Bello said the findings show how disease emerges when microbial communities reorganize themselves.
"This work shows that gut health is not just about which bacteria are present, but how they interact with one another," she said. "In diseases such as inflammatory bowel disease, C. difficile infection, irritable bowel syndrome and colorectal cancer, bacteria form more cooperative, tightly connected groups that can dominate and disrupt normal function."
Martin Blaser , an author of the study and director of Rutgers Health's Center for Advanced Biotechnology and Medicine , said the findings help explain why so many gut-related diseases have been difficult to predict and treat.
"This gives us a new way to think about what goes wrong in the microbiome," Blaser said. "Instead of focusing on individual microbes, it shows that disease emerges when the entire system shifts. That opens the door to earlier detection and more targeted interventions."
The team started their research by building computer models that simulate how gut bacteria compete for nutrients and exchange metabolic byproducts.
"At first we were just testing whether the model could reproduce basic features of real microbiomes," said Roberto Corral López, the study's lead author, who conducted the research as a Fulbright doctoral visiting student at Rutgers, and completed it at the Universidad de Granada in Spain. "But very early on, we saw that it naturally produced two distinct patterns."
That prompted the researchers to compare their simulations with DNA data from patients.
"When we checked the data, we saw the same pattern," said Corral López, also now a postdoctoral associate at the Instituto Carlos I de Física Teórica y Computacional in Spain. "That's when we realized we were capturing something fundamental about how these communities reorganize in disease."
The gut microbiome consistently settled into one of two configurations: a diverse, competitive state associated with health, and a second state dominated by small, tightly connected groups of cooperating bacteria linked to disease.
Bonachela said the insights and the tool could eventually help doctors identify problems earlier.
"In theory, it should be possible to measure it from just stool samples, which is a very non-invasive way to monitor gut health," he said.
The findings also may help explain why gut therapies such as probiotics and fecal microbiota transplants sometimes succeed and sometimes fail.
"Treatments are typically based on the idea that you need particular bacteria to be there," Bonachela said. "But if that is not the issue, if the issue is that key relationships are missing, then just adding the bacterium does not make a difference; it is necessary to recreate those relationships."
With fecal transplants, he said, the benefit may come not from introducing individual species, but from restoring entire microbial communities.
"The interesting aspect of fecal transplants is not that you introduce the species then," Bonachela said. "It is that you introduce a whole community, and therefore you are keeping the interactions that allow that community to be healthy. It is not that certain bacteria need to be there. They need to be there with the right partners."
Corral López said the work eventually could make microbiome-based therapies more predictable.
"Right now, donor selection is largely based on availability and basic health screening," said Corral López, referring to the process preceding fecal transplants. "Our work opens up the possibility of matching microbial communities based on how their interaction networks fit together, rather than just which species are present. That could help us design treatments that are tailored to each patient's microbiome instead of relying on trial and error."
Bonachela echoed that focus on practical impact.
"We are trying to understand how these systems work so we can make a real difference in people's lives," Bonachela said.
Michael Manhart of the Department of Biochemistry and Molecular Biology at Rutgers Robert Wood Johnson Medical School contributed to the study. Other contributors include Simon Levin of Princeton University and Miguel A. Munoz of the Universidad de Granada.
Explore more of the ways Rutgers research is shaping the future .
