What is already known
Pregnancy can predispose women to sepsis and to a higher mortality risk. However, the mechanisms leading to the immune perturbations behind these phenomena remain unclear.
What this research adds
Working in mice, researchers found that pregnancy causes changes in the microbiota composition. Reduced levels of Parabacteroides merdae during pregnancy leads to decreased formononetin (FMN), a potent anti-inflammatory agent. These alterations accelerate immune dysfunction associated with sepsis in pregnant animals. However, treating mice with P. merdae or FMN reduces sepsis-associated inflammation.
Conclusions
The findings reveal a microbe-immune axis that is disrupted in pregnant animals, suggesting potential therapeutic approaches for pregnancy-associated sepsis.
Sepsis — the body’s extreme response to an infection — can lead to serious complications during pregnancy, and is one of the main causes of maternal mortality in the United Kingdom. Now, a study done in mice reveals that pregnancy alters the gut microbiota in ways that accelerate immune dysfunction associated with sepsis.
The findings, published in Immunity, suggest potential therapeutic approaches for pregnancy-associated sepsis.
Scientists have known that pregnancy can predispose women to sepsis, but the mechanisms leading to the immune perturbations behind this phenomenon remain unclear. What’s more, the gut microbiota is known to modulate susceptibility to multiple organ failure — the hallmark of sepsis.
Because gut microbiota composition is reshaped during pregnancy, researchers led by Shenhai Gong at Southern Medical University set out to investigate the role of gut microbes in immune dysfunction in pregnant mice. To do so, they used a mouse model of sepsis, which consists in perforating the cecum to trigger the release of fecal material into the peritoneal cavity. This generates an infection that results in an exacerbated immune response.
Microbial shift
After cecum perforation, pregnant mice had a higher mortality rate than non-pregnant animals, and they were more susceptible to pneumonia induced by Pseudomonas aeruginosa.
However, compared with non-pregnant mice that received gut bacteria from non-pregnant donors, those that received gut bacteria from pregnant mice developed more severe organ injury in response to sepsis.
In both mice and women, pregnancy caused a shift in the gut microbiota composition as well as changes in microbial metabolites, the researchers found. In particular, the levels of Parabacteroides merdae and formononetin (FMN), a potent anti-inflammatory agent, were decreased in pregnant individuals.
Immune dysfunction
Further analyses showed that decreased P. merdae abundance resulted in lower FMN levels, indicating that the microbe may be involved in the progression of sepsis during pregnancy. Indeed, treating mice with P. merdae or FMN reduced sepsis-associated inflammation.
In septic mice, FMN inhibited the death of macrophages, a type of immune cell that kills pathogens and stimulates the activity of other immune cells. FMN also boosted the macrophages’ ability to surround and kill microorganisms.
Although the mechanisms responsible for pregnancy-associated reduction of P. merdae remain unknown, the results reveal a microbe-immune axis that may be leveraged to prevent or treat sepsis during pregnancy. “Our findings illustrate the cross talk between gut microbiota dysbiosis and immune dysfunction in [pregnant] septic hosts,” the researchers say.
