Probiotic Significantly Reduces S. aureus Colonization in Phase 2 Trial

New findings from a phase 2 clinical trial have found that using a probiotic instead of an antibiotic to control Staphylococcus aureus bacterial colonization was safe and highly effective, according to results published in The Lancet Microbe.

According to investigators, the probiotic Bacillus subtilis significantly reduced S. aureus colonization in trial participants without harming the gut microbiota and beneficial bacteria.

Methicillin-resistant S. aureus (MRSA) is a well known cause of disease, although S. aureus often lives on the body and in the gut without causing harm. However, if the skin barrier is broken or if the immune system is compromised, these bacteria can cause serious skin, bone, lung, and blood infections.

Preventing S. aureus infections with approaches to “decolonize” the body has gained attention as experts grow increasingly concerned about growing antibiotic resistance and limited treatment options. Some decolonization strategies are controversial because they also require large amounts of antibiotics, which could damage the microbiota and the development of antibiotic resistance.

According to the investigators, it currently appears that only nasal S. aureus colonization can be targeted using topical antibiotics without doing too much harm; however, bacteria can rapidly recolonize the nose from the gut. Probiotics may provide a solution, by complementing or replacing antibiotics.

Probiotic Bacillus is particularly promising because it is orally administered as spores that can survive passage through the stomach and then temporarily grow in the intestine. In earlier studies, investigators discovered an S. aureus sensing system necessary for these bacteria to grow in the gut. They also found that fengycins, Bacillus lipopeptides that are part peptide and part lipid, prevent the S. aureus sensing system from functioning, thereby eliminating the bacteria.

In the new clinical trial, conducted in Thailand, the investigators tested whether this approach works in humans. They enrolled 115 healthy participants, all of whom were colonized naturally with S. aureus.

A group of 55 participants received B. subtilis probiotic once daily for 4 weeks, whereas a control group of 60 participants received a placebo. After 4 weeks, researchers evaluated the participants’ S. aureus levels in the gut and nose.

According to the study, they found no changes in the control group. In the probiotic group, however, they observed a 96.8% S. aureus reduction in the stool and a 65.4% reduction in the nose.

“The probiotic we use does not ‘kill’ S. aureus, but it specifically and strongly diminishes its capacity to colonize,” said trial leader Michael Otto, PhD, in a press release.

The investigators noted that levels of S. aureus bacteria in the gut far exceeded S. aureus in the nose, which has long been the focus on staph infection prevention efforts. This finding adds to the potential role of S. aureus in the gut.

“Intestinal S. aureus colonization has been evident for decades, but mostly neglected by researchers because it was not a viable target for antibiotics,” Otto said in the press release. “Our results suggest a way to safely and effectively reduce the total number of colonizing S. aureus and also call for a categorical rethinking of what we learned in textbooks about S. aureus colonization of the human body.”

The investigators also plan to continue their work by testing the probiotic in a larger and longer trial. The approach probably does not work as quickly as antibiotics, but it can be used for longer periods because the probiotic does not cause harm as used in the clinical trial.

REFERENCE

Probiotic Markedly Reduces S. aureus colonization in phase 2 trial. News release. National Institute of Allergy and Infectious Diseases; January 17, 2023. Accessed January 24, 2023. https://www.niaid.nih.gov/news-events/probiotic-markedly-reduces-s-aureus-colonization-phase-2-trial