Antibiotics have been the cornerstone of therapeutic interventions for bacterial infections. However, their use has become limited as these pathogens develop resistance to these drugs. Therefore, recently approved drugs may have diminished utility in the near future as these pathogens evolve. In light of this, some researchers are proposing a new treatment paradigm against these pathogens: probiotics.
Probiotics are microorganisms that are non-toxic, non-pathogenic, lack the ability to acquire antibiotic resistance, and provide health benefits [1]. Probiotics must be able to survive and grow within the gastro-intestinal tract as they are administered orally. Species like Lactobacillus are naturally found in yogurt and other fermented foods. These bacteria are beneficial since they can out compete other pathogens by binding to the surface of cells and stimulate the mucosal immune system. Recently, peptides produced by Bacillus were found to be effective against Staphylococcus aureus.
Staphylococcus aureus is a commensal bacteria that colonizes the skin and mucosal membranes within the nose up to 50% of the population either intermittently or chronically [2]. While colonized individuals are asymptomatic, harm arises when the bacterium enters the bloodstream through wounds, surgical sites and implantation of devices and prosthetics. S. aureus can cause disease in nearly every tissue in the body, including the brain and bones. Toxins expressed by the bacterium facilitate the development of these diseases [3,4]. Historically, S. aureus infections have disproportionately impacted vulnerable populations like the elderly and immune-compromised, but in recent decades there has been a rise in infections of healthy individuals. Research at the National Institutes of Health suggests that S. aureus colonization can be diminished through probiotic use, and ultimately prevent the likelihood of infection.
A research team led by Dr. Otto found a correlation between the presence of Bacillus bacteria and the absence of S. aureus, suggesting that Bacillus may inhibit S. aureus colonization [5]. Furthermore, they identified fengycin, a lipopeptide that is produced by Bacillus. Fengycin can outcompete S. aureus signaling peptides and interfere with the quorum sensing system in S. aureus. Quorum sensing is the ability of bacteria to respond based on cell density (in other words, bacteria population) and Otto’s group found that this system encourages bacteria colonization. When this system is inhibited by Bacillus fengycin, S. aureus colonization is also reduced.
This approach was investigated in humans, with results from a phase 2 trial shared earlier this year. The results suggest that Bacillus probiotics can limit S. aureus colonization in the gut and nose [6]. The treatment group took a daily probiotic for 4 weeks and showed over a 90% reduction of S. aureus in stool and 65% reduction in the nose. This approach also left the healthy gut microbiota intact, unlike antibiotics that target both beneficial and harmful bacteria alike. The efficacy of probiotics will continue to be investigated in a longer and larger trial.
While it takes longer to see benefits from probiotics (2-3 weeks), establishing its efficacy in combatting pathogenic bacterial growth may provide new avenues towards bacterial infections. This is especially significant in the context of reoccurring infections and those that may be more susceptible to infection overall, such as individuals with chronic illness. Probiotics may be the first step in updating our medicinal arsenal against infectious disease.
References:
1. Lopez-Santamarina, A. et al. Probiotic Effects against Virus Infections: New Weapons for an Old War. Foods 10, (2021).
2. Lee, A. S. et al. Methicillin-resistant Staphylococcus aureus. Nature Reviews Disease Primers 2018 4:1 4, 1–23 (2018).
3. Liu, G. Y. Molecular Pathogenesis of Staphylococcus aureus Infection. Pediatric Research 2009 65:7 65, 71–77 (2009).
4. Thomer, L., Schneewind, O. & Missiakas, D. Pathogenesis of Staphylococcus aureus Bloodstream Infections. Annu Rev Pathol 11, 343 (2016).
5. Piewngam, P. et al. Pathogen elimination by probiotic Bacillus via signalling interference. Nature 2018 562:7728 562, 532–537 (2018).
6. Piewngam, P. et al. Probiotic for pathogen-specific Staphylococcus aureus decolonisation in Thailand: a phase 2, double-blind, randomised, placebo-controlled trial. Lancet Microbe 4, e75–e83 (2023).