Systems-ecology designed bacterial consortium protects from severe Clostridioides difficile infection

Area of Science:

• Microbiology
• Systems Biology
• Gastroenterology

Background:

• Fecal Microbiota Transplant (FMT) is effective for recurrent Clostridioides difficile infection (rCDI).
• FMT carries risks, including antimicrobial resistance transfer, driving the need for safer bacteriotherapies.
• Targeted approaches are needed to address C. difficile pathogenesis.

Approach:

• Developed a systems biology pipeline to identify probiotic candidates.
• Analyzed metagenomic data from FMT donors to find key metabolic pathways.
• Reconstructed microbial metabolism to simulate interactions with C. difficile.

Key Points:

• Identified amino acid cross-feeding as a critical metabolic interaction in successful FMT.
• Assembled bacterial consortia with enhanced cross-feeding capabilities.
• Validated these consortia in vitro and in a murine model of CDI, showing protection.

Conclusions:

• Amino acid cross-feeding is a key mechanism in resolving CDI.
• The predictive platform enables rational design of targeted biotherapeutics.
• This framework can be extended to other enteric infections.