Identification of antimicrobial peptides from ancient gut microbiomes

Area of Science:

• Microbiology
• Biochemistry
• Bioinformatics

Background:

• Ancient fecal coprolites harbor preserved microbiomes.
• Antimicrobial peptides (AMPs) are crucial for innate immunity.
• Extinct AMPs from ancient microbiomes represent a potential source of novel therapeutics.

Purpose of the Study:

• To develop an efficient tool (AMPLiT) for screening AMPs in metagenomic data.
• To identify and characterize novel AMPs from ancient human coprolites.
• To investigate the therapeutic potential of AMPs derived from Segatella copri.

Main Methods:

• Development of AMPLiT, a lightweight tool for AMP identification in metagenomic datasets.
• Computational analysis of seven ancient human coprolite metagenomes using AMPLiT.
• Synthesis and in vitro antimicrobial activity testing of 40 candidate AMPs.
• In vivo evaluation of lead peptides for antibacterial and wound-healing efficacy.

Main Results:

• AMPLiT demonstrated high performance (AUPRC 0.9486) and efficient training time.
• 160 AMP candidates were identified, with 90% showing in vitro antimicrobial activity.
• Two-thirds of active AMPs were derived from Segatella copri.
• S. copri-derived AMPs exhibited potent antibacterial activity against pathogens, low cytotoxicity, and effective wound healing in vivo.

Conclusions:

• Ancient gut microbiomes are a valuable source of novel, highly efficacious AMPs.
• Segatella copri, an underrepresented ancient commensal, produces potent AMPs with therapeutic potential.
• These findings provide insights into the historical role of S. copri in human health and its decline in modern populations.