Feeding mice a probiotic of harmless bacteria helps prevent harmful microbes entering the blood where they could build up and potentially cause a condition called sepsis
24 November 2021
Consuming a type of bacterium that is commonly found in soil helps mice avoid a blood infection that could potentially lead to sepsis, and the research might one day lead to treatments for people too.
Sepsis results from the activity of bacteria, including Enterococcus faecalis. These microbes can live in the human gut without causing disease, but in people who take antibiotics for prolonged periods, or treatments that weaken their immunity, E. faecalis can spread into the blood where it can cause body-wide infection. This is sepsis.
Now, for the first time, there is evidence from experiments in mice that consuming a probiotic can prevent blood infection. The probiotic was in the form of spores from another type of bacterium, Bacillus subtilis. These spores are dormant forms of the bacterium that don’t reproduce themselves and are highly resistant to environmental damage. On entering the gut, they activate and grow, influencing the growth of other bacteria in the intestine.
Michael Otto at the National Institute of Allergy and Infectious Diseases in Maryland and his colleagues first mimicked the treatment that people with blood cancer often receive, by giving mice the chemotherapeutic drug cyclophosphamide for a few days and then following this up with a cocktail of antibiotics.
The team then fed mice with two doses of either B. subtilis spores or a salt solution before a dose of E. faecalis the following day. The next day, the mice that had received the salt solution placebo treatment did have E. faecalis in their blood, where it could potentially cause sepsis, but those that had received the probiotic avoided blood infection.
Although neither group of mice had bacteria in the blood after three days, probably because the immune system cleared the microbes away, the team found E. faecalis in the liver and spleen of control mice at this stage, but not in the mice fed with the probiotic.
The team found that E. faecalis produces enzymes that made the gut leakier, helping them spread into the blood, and say the probiotic could be preventing this effect.
To test this idea, the group fed mice with a non-digestible fluorescent chemical, and then measured how much of this marker was present in the blood 4 hours later. The concentration of the marker was more than twice as high in mice that had received the placebo as it was in those that received probiotic. This suggests that the probiotic does counteract an increase in gut leakiness.
Consistent with this finding, the gut linings of mice treated with the placebo had hugely disorganised structures compared with mice treated with probiotic. The guts of placebo mice completely lacked villi, finger-like projections in the gut wall that absorb nutrients from food.
It is important to note that this work defines specific bacteria that can prevent sepsis caused by another particular species of bacterium, says Otto. This marks a distinction from the claims often made for other probiotics that suggest they have broad health benefits but without offering much detailed understanding of the process, says Otto.
“Addressing sepsis in a safe manner has large public health implications, particularly these days when microbial infections have never been so dramatically in the public eye,” says Glenn Gibson at the University of Reading, UK.
Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.abf4692
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