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 antimicrobial peptide resistance genes (AMPRGs) of gut microbes in different age groups has 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. Additionally, 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 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.

中文翻译：

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来自百岁老人肠道微生物组的抗菌肽：生物合成的多样化和耐药基因的年轻化发育


抗菌肽 （AMP） 由于其抗菌特性，为抗生素危机提供了潜在的解决方案，而人类肠道生物群落可能是这些肽的来源。然而，不同年龄组肠道微生物的潜在 AMPs 和抗菌肽耐药基因 （AMPRG） 尚未得到彻底评估。在这里，我们通过分析不同生命阶段健康个体的肠道宏基因组数据（CG：百岁老人组 n=20;OAG：老年人组 n=15;YG：年轻组 n=15）。在肠道微生物组中的潜在 AMP 中观察到与年龄相关的增加，百岁老人表现出这些肽的多样性更大。然而，与 OAG 组相比，CG 组的肠道微生物组 AMPRGs 水平较低，与 YG 组相似。此外，常规益生菌菌株与某些潜在的 AMPs 呈显著正相关，并且与抗性基因的检测较低相关。此外，将潜在的 AMP 与现有文库进行比较揭示了有限的相似性，这表明当前的机器学习模型可以识别肠道微生物群中的新肽。这些结果表明，长寿可能受益于 AMP 的多样性和较低的抗性基因。我们的研究结果有助于解释百岁老人的年龄优势，并确定人类肠道微生物组中抗菌肽生物合成的潜力，为抗菌肽耐药性的发展和益生菌菌株的筛选提供见解。