Uncovering the gut microbiome and antibiotic resistome of mammals on the Tibetan Plateau.

The mammalian species on the Tibetan Plateau are diverse and abundant, yet our understanding of their gut microbiome and antibiotic resistome remains limited. Here, we used metagenomics to analyse the gut microbiota of 2,561 mammals from the Tibetan Plateau, covering 14 species across six orders. Using de novo metagenome assembly, we reconstructed a total of 112,313 high- to medium-quality metagenomic assembly genomes (MAGs), representing 21,902 microbial species, 86% of which were unclassified. More than 8,000 nonredundant antibiotic resistance genes (ARGs) encompassing 28 types were identified in the gut microbiome of Tibetan Plateau mammals. We further conducted a risk assessment of these ARGs, identifying 334 nonredundant ARGs with high-risk characteristics related to human health. Importantly, seven cross-species horizontal gene transfer events involving high-risk ARGs were identified, three of which occurred between human and nonhuman mammalian gut microbiota. Additionally, we found that the abundance of ARGs in human gut microbiomes on the Tibetan Plateau was greater than that in those from eastern China, Europe, and the United States, whereas the abundance of ARGs in livestock gut microbiomes from the Tibetan Plateau was lower than that in livestock gut microbiomes from those regions. This study reveals that the gut microbiota of Tibetan Plateau mammals is a largely unexplored resource and a significant reservoir of ARGs, offering crucial insights into microbiome research and demonstrating potential public health implications.