Comprehensive metagenomic survey reveals vast gut microbiome diversity and antibiotic resistome across 14 mammal species on the Tibetan Plateau

This research, led by Zhigang Zhang, Li Yu and colleagues from Yunnan University and collaborators, provides the most comprehensive genomic catalogue to date of mammalian gut microbiomes from the Tibetan Plateau. Between 2016 and 2022, the team collected 2,561 gut metagenomic samples across 14 mammalian species and six orders, including humans, livestock and wildlife.

Using de novo metagenome assembly and rigorous binning and quality control, the authors reconstructed 112,313 high- to medium-quality metagenome-assembled genomes (MAGs), which clustered into 21,902 species-level genome bins; 86% of these species-level bins could not be matched to known species, indicating a large reservoir of previously uncharacterized microbes.

Analysis of antibiotic resistance genes revealed 8,598 nonredundant ARGs covering 28 resistance types. The study applied a risk-classification framework to identify 334 nonredundant ARGs with high-risk characteristics for human health. Seven high-risk ARG horizontal gene transfer (HGT) events were predicted across species, and three of these events involved transfer between human and nonhuman mammalian gut microbiota. Escherichia coli emerged as a dominant ARG host, with many E. coli MAGs carrying multiple multidrug resistance genes.

Comparative analyses with external low-altitude datasets showed that human gut microbiomes on the Tibetan Plateau harboured a higher ARG abundance and greater richness of high-risk ARGs than comparator populations from eastern China, Europe and the United States, whereas livestock from the Tibetan Plateau showed lower ARG abundance than livestock from those regions. These geographic contrasts underscore the complexity of regional drivers—environmental reservoirs, host diet and livestock management practices—that shape resistome distributions.

The authors note that most core ARGs across species are low-risk, but the sharing of high-risk core ARGs—particularly between Tibetan people and Tibetan pigs—highlights potential transmission pathways at the human–animal interface. The manuscript stresses One Health implications and recommends continued surveillance integrating human, animal and environmental sampling to clarify transmission routes and mitigate risks.

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