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A Bacillus subtilis probiotic demonstrated the ability to wipe out most Staphylococcus aureus colonization without altering the gut microbiome, a placebo-controlled phase II study conducted in Thailand showed.

Of 115 healthy individuals with natural S. aureus colonization, 30 days of the probiotic led to a 96.8% reduction in S. aureus in stool (P<0.0001) and a 65.4% reduction in the nose (P=0.0002), reported Michael Otto, PhD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and colleagues.

Meanwhile, no reductions of S. aureus in the gut or nose were observed among individuals assigned to placebo, the group reported in .

"This method achieves that which was previously impossible, a reduction of a large portion (>95%) of the total number of S. aureus colonies in humans, without adverse side-effects," wrote Otto and colleagues, adding that the approach "even affects S. aureus numbers in the nose as a colonization site distal to the site of intervention."

S. aureus infections kill more people than any other antibiotic-resistant pathogen, with an annual estimated death toll of 20,000 in the U.S. Less well known is that the pathogen is carried asymptomatically by many individuals -- roughly a third of the population -- putting them at risk of serious infections.

In the past, oral antibiotic treatment has been the only option for targeting S. aureus colonization, but the Infectious Diseases Society of America advises against such an approach as it can spur on antibiotic resistance, such as methicillin-resistant S. aureus (MRSA); eliminate good bacteria in the gut; and also propagate other infections including Clostridioides difficile.

As a probiotic, B. subtilis is promising as it can survive passage through the stomach, and its fengycin production prevents "the S. aureus sensing system from functioning, thereby eliminating the bacteria," according to a from the NIH.

"The probiotic we use does not 'kill' S. aureus, but it specifically and strongly diminishes its capacity to colonize," Otto said in the release. "We think we can target the 'bad' S. aureus while leaving the composition of the microbiota intact."

In an that accompanied the study, Otto explained that the probiotic isn't a quick fix, and it cannot be used for treating serious S. aureus infections, but it could have clinical potential. In long term-care facilities where people are at increased risk, for example, it could be deployed to lower infection rates. Hemodialysis patients also have a "super increased risk" and may be a targetable population, he added.

While past research primarily focused on eliminating S. aureus in the nose, the researchers noted, large numbers of S. aureus colonies are found in the intestine.

"Our findings indicate a pivotal role of the intestinal S. aureus colonization site and call for a categorical rethinking of S. aureus colonization dynamics and the setup of S. aureus decolonization strategies," wrote Otto and colleagues, concluding that "decolonization efforts should generally focus on intestinal rather than, or at least in addition to, nasal colonization."

For their single-center study, the researchers enrolled and screened 611 eligible adult participants from the Songkhla region of Thailand from January to April 2021, and screened them for S. aureus colonization. (Participants who were pregnant, breastfeeding, taking probiotics, or had diarrhea were excluded from enrollment.)

The 115 individuals (19%) with S. aureus were randomized to 30 days of the oral probiotic (250 mg of probiotic B. subtilis MB40; n=55) or matching placebo (n=60).

Participants had a mean age of 34-36 years, and 63% were women. Intestinal-only colonization was detected in 65 participants, nasal-only colonization was detected in 31 participants, and the remaining 19 had colonization in both the gut and nose.

No severe adverse events (AEs) were reported during the study, and moderate AEs were rare and not significantly more frequent than with placebo.

A limitation of the trial is that it was performed in rural Thailand, although the study authors said they expect to find similar results in other geographical areas. Also, they noted that baseline colonization was higher in the placebo group -- though not significantly -- but still said this would have had a "minor effect" on outcomes.

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