A probiotic bacterium could help prevent severe blood infections

Bacterial spores of the probiotic Bacillus subtilis can prevent dangerous Enterococcus bacteria from invading the blood and causing systemic infections.
Table of Contents

What is already known on this topic
Probiotics are foods or supplements that contain live microorganisms intended to maintain the normal gut microflora. Although probiotics appear to reduce the abundance of pathogens within the intestinal microbiota, whether and how they promote human health remains controversial. It’s also unclear if probiotics can reduce systemic infections such as those caused by the gut bacterium Enterococcus faecalis, which can cause blood infections in hospitalized people and those with a weakened immune system receiving antibiotic treatment.

What this research adds
Working in mice, researchers found that translocation of Enterococcus faecalis from the gut into the blood is mediated by a communication mechanism between bacteria called Frs quorum-sensing, which triggers the production of an enzyme that compromises the integrity of the gut epithelium. E. faecalis translocation from the gut to the blood and the subsequent systemic infection in mice could be blocked by administering spores of the probiotic Bacillus subtilis.

Conclusions
The findings suggest that probiotic Bacillus spores may prevent Enterococcus systemic infections in at-risk people.

Probiotics have been touted as a treatment for a vast range of conditions, but whether and how they promote human health remains controversial. Now, a study in mice indicates that bacterial spores of the probiotic Bacillus subtilis can prevent dangerous Enterococcus bacteria from invading the blood and causing systemic infections.

The findings, published in Science Translational Medicine, suggest that probiotic Bacillus spores may prevent Enterococcus systemic infections in at-risk people. 

Probiotics — foods or supplements that contain live microorganisms intended to maintain the normal gut microflora — appear to reduce the abundance of pathogens within the intestinal microbiota. For example, studies have shown that probiotics suppress the growth of disease-causing Salmonella in the gut, either by stimulating the immune system or directly killing these bacteria. 

However, it’s unclear whether probiotics can also reduce systemic infections outside the gut, such as those caused by the gut bacterium Enterococcus faecalis. E. faecalis is an opportunistic pathogen that can cause blood infection, especially in hospitalized people and those with a weakened immune system receiving antibiotic treatment.

To monitor Enterococcus infections, Michael Otto at the U.S. National Institutes of Health and his colleagues set up a mouse model that mimics conditions such as antibiotic therapy and immune depletion, which lead to Enterococcus overgrowth in the human gut.

Causing infection

The researchers found that E. faecalis bacteria penetrated the intestinal lining and entered the bloodstream through a communication mechanism between bacteria called Frs quorum-sensing. This cell-to-cell communication system appears to be critical for E. faecalis translocation from the mouse gut into the blood, the authors say.

Indeed, further experiments showed that Fsr quorum-sensing triggers the production of an enzyme called GelE, which compromises the integrity of the gut epithelium. 

Interfering with quorum-sensing systems could be a promising strategy for countering the detrimental effects of disease-causing bacteria, the researchers note. “Fsr inhibitors have been identified, but their therapeutic usefulness for eliminating systemic infection is unclear,” they add. 

Probiotic spores

Previous work by Otto’s team has showed that probiotic B. subtilis spores administered orally can germinate in the gut and eliminate Staphylococcus aureus intestinal colonization by reducing the bacterium’s quorum-sensing. So, the team set out to use probiotic B. subtilis spores to block Enterococcus’ Fsr quorum-sensing system. 

When given to mice before exposure to E. faecalis, oral doses of Bacillus spores blocked the gene that encodes GelE. This prevented E. faecalis translocation from the gut to the blood and the subsequent systemic infection.

The results shed light on how Enterococcus invades the bloodstream from its usual niche in the gut. They also demonstrate, the researchers add, “that a key aspect of Enterococcus pathogenesis is controlled by quorum sensing, which can be targeted with probiotic Bacillus spores.”