New mouse research links gut microbiome differences to sepsis severity, adding evidence that gut health may influence how the immune system responds to infection.
Differences in the gut microbiome may help explain why sepsis becomes far more dangerous in some cases than others, according to a new study published in Nature that found certain gut bacteria worsened outcomes in mouse models.
The research, conducted by scientists at the Korea Research Institute of Bioscience and Biotechnology’s Infectious Disease Research Center, examined genetically similar female mice with different gut microbiomes. The mice were infected with Acinetobacter baumannii , a resilient bacterium that can lead to sepsis.
Sepsis is a potentially deadly reaction to infection, and outcomes can vary sharply even when the infection appears similar. The new findings suggest the makeup of the gut microbiome may influence how aggressively the immune system responds before an infection has taken hold. The evidence, however, comes from animal research, and an outside infectious disease specialist cautioned that more work is needed before drawing conclusions for human patients.
Researchers compared mice with higher and lower survival rates, looking at gut bacteria, bacterial levels in the blood and organs, and cellular markers. Mice with poorer survival had a much higher share of Muribaculaceae bacteria in the gut — about 28% of the microbiome in one comparison, versus 0.15% in mice that survived at higher rates.
Those more vulnerable mice showed an early, intense inflammatory response and later had more bacteria in the blood, lungs and spleen. One bacterial strain, Sangeribacter muris KT1-3, stood out in mice with worse survival. When mice that typically had high survival rates were housed with KT1-3 mice, their survival dropped to 10%, according to the reported findings.
Andrew Fleming, section chief of infectious diseases and immunology at NYU Langone Hospital, Brooklyn, who was not involved in the study, said scientists have long known that gut bacteria and bacterial toxins can enter the bloodstream during sepsis and intensify inflammation. “This process is particularly important in septic shock, where the intestinal wall becomes more permeable to translocation (or leaking) of bacterial products,” Fleming said.
Fleming said there is growing evidence that a diverse, healthy gut microbiome may be protective in some ways against severe sepsis, while a disrupted microbiome — including one heavily affected by antibiotics — may impair the immune response. He also noted that antibiotics can have major, lasting effects on the microbiome, and cited CDC estimates that up to 80% of U.S. adults receive an antibiotic each year, with roughly 30% considered unnecessary.
The study’s limits are important. Fleming said Sangeribacter muris is not typically found in humans, meaning the mechanism shown in the mouse study cannot be directly applied to people. He called the findings an intriguing starting point and said well-designed clinical trials are needed to determine whether similar microbiome effects influence sepsis severity in humans.
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