A Microbial Consortia That Depresses Klebsiella Pneumoniae

SUMMARY

• Drug-resistant Enterobacteriaceae (particularly K. pneumoniae) are a growing cause of hospital-acquired infections, pneumonia, and antibiotic failure. Broad-spectrum antibiotics exacerbate dysbiosis and resistance, while fecal microbiota transplant lacks standardization, mechanistic clarity, and regulatory scalability. Existing probiotics poorly predictive, leaving a critical gap for precision, reproducible microbiome therapeutics that reliably clear resistant pathogens.

• The therapeutic microbiome consortia uses machine learning to design microbial communities with emergent pathogen-suppressive function. By screening thousands of synthetic consortia and learning strain-to-strain interactions predictive of clearance, our researchers identified compact, high-performing communities (e.g., 15-strain SynCom15) that consistently suppress K. pneumoniae. These consortia act through metabolic reprogramming of the gut environment (including short-chain fatty acid enrichment and amino-acid depletion) while engrafting stably and restoring microbiome diversity.

ADVANTAGES

ADVANTAGES

• Predictive design, not trial-and-error: ML-guided consortium engineering with validated out-of-sample performance

• Defined & reproducible: Fully characterized strains with genome-level identity and controlled composition

• FMT-like efficacy: Matches or exceeds fecal microbiota transplant performance in preclinical models with superior standardization

• Broad-spectrum resistance coverage: Effective against drug-resistant and carbapenem-resistant Enterobacteriaceae

• Mechanistically grounded: Links strain composition to metabolic outputs and pathogen suppression

PUBLICATIONS

• Oliveira RA, McSpadden E, Pandey B, Lee K, Yousef M, Chen RY, Triebold C, Haro F, Aksianiuk V, Patel R, Shriram K, Ramanujam R, Kuehn S, Raman AS. Statistical design of a synthetic microbiome that suppresses diverse gut pathogens. bioRxiv [Preprint]. 2025 Dec 31:2024.02.28.582635. doi: 10.1101/2024.02.28.582635. PMID: 41502951; PMCID: PMC12773023.

• Shown effective in both in vitro and in vivo studies