Winter Caching of Artemisia frigida Is Associated With Host Physiological and Gut Microbial Variation in Brandt's Voles

Seasonal variation in food resources represents a major ecological challenge for wild herbivores, yet how naturally selected dietary resources become associated with host and microbial responses remains poorly understood. During winter, Brandt's voles (Lasiopodomys brandtii) cache large amounts of Artemisia frigida, suggesting that this plant may have ecological significance beyond its nutritional value. However, the biological basis underlying this seasonal food preference remains unclear. Here, using Brandt's voles as a model system, we investigated whether the naturally selected winter food A. frigida was associated with coordinated variation in host physiology and gut microbial organization under cold conditions. By integrating physiological phenotyping, hypothalamic neuroendocrine analyses, adipose tissue transcriptomics, shotgun metagenomics and metagenomic binning, we characterized host and microbial responses across multiple biological levels. Dietary A. frigida was associated with altered hypothalamic AgRP expression, increased UCP1 expression in BAT and transcriptional changes related to lipid metabolism and thermogenic pathways during cold exposure. Supplement of A. frigida was associated with changes in gut microbial community structure, enrichment of specific bacterial taxa and shifts in predicted microbial functional potential. Genome-resolved analyses further reconstructed 277 non-redundant metagenome-assembled genomes, enabling assessment of microbial ecological variation associated with seasonal food conditions. Together, our findings provide molecular ecological evidence linking winter caching of A. frigida with coordinated variation in host physiology and gut microbial organization, highlighting seasonal dietary resources as an overlooked component of ecological variation in wildlife.