Antimicrobial Peptides From the Gut Microbiome of the Centenarians: Diversification of Biosynthesis and Youthful Development of Resistance Genes

Abstract Antimicrobial peptides (AMPs) offer a potential solution to the antibiotic crisis owing to their antimicrobial properties, and the human gut biome may be a source of these peptides. However, the potential AMPs and AMP resistance genes (AMPRGs) of gut microbes in different age groups have not been thoroughly assessed. Here, we investigated the potential development of AMPs and the distribution pattern of AMPRGs in the gut microbiome at different ages by analyzing the intestinal metagenomic data of healthy individuals at different life stages (CG: centenarians group n = 20; OAG: older adults group: n = 15; YG: young group: n = 15). Age-related increases were observed in the potential AMPs within the gut microbiome, with centenarians showing a greater diversity of these peptides. However, the gut microbiome of the CG group had a lower level of AMPRGs compared to that of the OAG group, and it was similar to the level found in the YG group. Additionally, conventional probiotic strains showed a significant positive correlation with certain potential AMPs and were associated with a lower detection of resistance genes. Furthermore, comparing potential AMPs with existing libraries revealed limited similarity, indicating that current machine learning models can identify novel peptides in the gut microbiota. These results indicate that longevity may benefit from the diversity of AMPs and lower resistance genes. Our findings help explain the age advantage of the centenarians and identify the potential for antimicrobial peptide biosynthesis in the human gut microbiome, offering insights into the development of antimicrobial peptide resistance and the screening of probiotic strains.