In 2015, Audrey Wiggins was a healthy 31-year-old when she mistook her severe illness for the flu.

It turned out to be sepsis, a life-threatening condition that placed her in intensive care for 10 days, including five spent in a medically induced coma.

A new study suggests that the gut may hold hidden factors that influence who becomes more susceptible to severe sepsis.

Researchers from the Korea Research Institute of Bioscience and Biotechnology’s Infectious Disease Research Center investigated this link using female mouse models to understand why sepsis outcomes can differ so widely among patients.

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The study, published in *Nature*, examined mice that were genetically similar but carried different mixes of gut bacteria. Each mouse was infected with Acinetobacter baumannii, a resilient bacterium known to cause sepsis.

The research team compared groups with higher and lower survival rates, analyzing variations in microbiome composition, bacterial spread to organs, and immune activity.

According to their findings, some mice harbored higher levels of bacteria belonging to the Muribaculaceae family. In poorly surviving mice, these bacteria comprised about 28% of their gut microbiome compared to just 0.15% in those that survived better.

Animals with poorer survival mounted stronger early inflammatory responses, which later led to increased bacterial presence in their blood, lungs, and spleen. The results suggest that preexisting microbial differences can influence how the immune system reacts when infection occurs.

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The team also observed that one particular bacterial strain, Sangeribacter muris KT1-3, was especially abundant in mice that fared poorly. When typically resilient mice were housed with those carrying the KT1-3 strain, their survival rate dropped to 10%, pointing to a potential microbial influence on sepsis severity.

These results hint that gut microbiome makeup may affect immune behavior before any infection develops.

Andrew Fleming, MD, section chief of Infectious Diseases & Immunology at NYU Langone Hospital in Brooklyn, said it has long been known that gut bacteria and their toxins can pass into the bloodstream during sepsis. This, he explained, worsens inflammation linked to the initial infection.

“This process is particularly important in septic shock, where the intestinal wall becomes more permeable to translocation of bacterial products,” Fleming said.

He described interactions between the gut microbiome and the immune system as “complex and variable from person to person.” However, he noted growing evidence that a diverse and balanced microbiome appears to offer protection against severe sepsis, while one thrown off balance—sometimes by antibiotics—can make the body’s defense system less effective.

Fleming compared the gut microbiome to a “living organ” that, like the heart, kidneys, or liver, performs many vital roles in maintaining health.

He added that an unhealthy microbiome can affect the body in several ways, including its ability to fight infections.

“Compared to our other organs, we currently have fewer readily available tests in the doctor’s office to measure the health of our microbiome,” he said. “However, this should not prevent us from thinking about our gut microbiome and how to keep it healthy.”

He also highlighted how antibiotic use can have “major and long-lasting effects” on the gut. According to the Centers for Disease Control and Prevention, up to 80% of U.S. adults are prescribed an antibiotic each year, and about 30% of those prescriptions may be unnecessary.

“Antibiotics deplete the diversity of the microbiome and create a void in the gut microbial community that can be filled by harmful bacteria from the environment,” Fleming explained. “We must begin to think much more critically about our antibiotic use and overuse, both to maintain our gut health and to reduce the spread of antibiotic resistance.”

While the sepsis study provided intriguing data, Fleming emphasized its limitations. Sangeribacter muris is not a bacterium typically found in humans, so its role in sepsis cannot be directly applied to people. He said more clinical trials are needed to explore similar mechanisms in human patients.

Even so, he said the findings reinforce the notion that a healthy gut microbiome may help regulate immune function and reduce vulnerability to severe sepsis.