Systematically investigating and identifying bacteriocins in the human gut microbiome.

Area of Science:

• Microbiology
• Bioinformatics
• Molecular Biology

Background:

• Unmodified bacteriocins are natural antimicrobial peptides produced by the human gut microbiota.
• These peptides play roles in pathogen protection and host physiology regulation.
• Current bioinformatics tools hinder comprehensive investigation of bacteriocin biosynthesis and function.

Purpose of the Study:

• To introduce IIBacFinder, a novel analysis pipeline for identifying unmodified class II bacteriocins.
• To investigate the distribution and biosynthetic potential of bacteriocins in the human gut microbiome.
• To experimentally validate the antibacterial activity and host microbiota impact of synthesized bacteriocins.

Main Methods:

• Developed and applied the IIBacFinder analysis pipeline.
• Conducted large-scale bioinformatic analysis of over 280,000 bacterial genomes.
• Utilized meta-omics analysis, chemical synthesis, and experimental validation (in vitro and ex vivo).

Main Results:

• IIBacFinder enables superior identification of unmodified class II bacteriocins.
• Bacteriocins are widespread across bacteria, often habitat-specific.
• Human gut bacteria possess diverse bacteriocin biosynthetic potential; 16 of 26 synthesized hypothetical bacteriocins showed activity.
• Synthesized narrow-spectrum bacteriocins had minimal impact on human fecal microbiota ex vivo.

Conclusions:

• The human gut harbors significant, largely untapped, biosynthetic potential for unmodified bacteriocins.
• IIBacFinder facilitates deeper understanding of bacteriocin roles in the gut microbiome.
• This research opens avenues for exploring bacteriocins' health implications and therapeutic applications.