Computational andin vitroevaluation of probiotic treatments for nasalStaphylococcus aureusdecolonization
Authors: Tepekule Burcu , Barcik Weronika , Staiger Willy I. , Bergadà-Pijuan Judith , Scheier Thomas , Brülisauer Laura , Hall Alex , Günthard Huldrych F. , Hilty Markus , Kouyos Roger D. , Brugger Silvio D. 
Published: August 2022

AbstractDespite the increasing burden of antibiotic resistance and persistence, current approaches to eradicate nasal pathobionts such asStaphylococcus aureusandStreptococcus pneumoniaeare based on the use of antibacterial agents. An alternative approach is the artificial inoculation of commensal bacteria, i.e., probiotic treatment, which is supported by the increasing evidence for commensal-mediated inhibition of pathogens. To systematically investigate the potential and the limitations of this approach, we developed a quantitative framework simulating the dynamics of the nasal bacterial microbiome by combining mathematical modeling with longitudinal microbiota data. By inferring the microbial interaction parameters using 16S rRNA amplicon sequencing data and simulating the nasal microbial dynamics of patients colonized withS. aureus, we compared the decolonization performance of probiotic and antibiotic treatments under different assumptions on patients’ bacterial community composition and susceptibility profile. To further compare the robustness of these treatments, we simulated aS. aureuschallenge following each treatment and quantified the recolonization probability. Eventually, using nasal swabs of adults colonized withS. aureus, we confirmed that after antibiotic treatment, recolonization ofS. aureuswas inhibited in samples treated with a probiotic mixture compared to the non-treated control. Our results suggest that probiotic treatment clearly outperforms antibiotics in terms of decolonization performance, recolonization robustness, and leads to less collateral reduction of the microbiome diversity. Moreover, we find that recolonization robustness is highest in those patients that were not initially colonized byDolosigranulum pigrum. Thus, probiotic treatment may provide a promising alternative to combat antibiotic resistance, with the additional advantage of personalized treatment options via using the patient’s own metagenomic data to tailor the intervention. The combination of anin silicoframework within vitroconfirmatory experiments using clinical samples reported in this work is an important step forward to further investigate this alternative in clinical trials.ImportanceThe development of new antimicrobial agents is declining while antibiotic resistance is rising, which is particularly concerning for upper respiratory tract pathogensS. pneumoniaeandS. aureus. Combating such resistant infections will only become more challenging unless alternative treatment strategies are explored. Despite the accumulating evidence on using commensal bacteria for pathobiont decolonization, it is still not commonly practiced. To investigate the potential of commensal-mediated inhibition of pathogens systematically, we developed a quantitative framework describing the dynamics of the nasal microbiome by merging mathematical modeling and metagenomic data. We show that probiotic treatment outperforms antibiotics regarding decolonization performance and recolonization robustness while preserving the microbiome diversity with the additional advantage of personalized treatment options via using the patient’s own microbiota data. Moreover, we validated the approach by using nasal swabs from adults with nasalS. aureuscolonization, demonstrating that probiotic treatment prevents recolonization withS. aureus in vitro. The framework developed in this work is an important step forward for the translation of experimental and clinical data into mainstream clinical practice in a systematic and controlled manner.