The combined influence of microbiome and soil environment contributes to the chemotype differentiation in...

Atractylodes lancea, a traditional Chinese medicinal herb, is divided into two chemotypes based on the production of volatile bioactive compounds: the geo-authentic Maoshan chemotype (MSA, rich in atractylon and atractylodin) and the non-authentic Hubei chemotype (HBA, dominated by hinesol and β-eudesmol). However, the mechanisms underlying the differentiation of these chemotypes remain poorly understood. By sequencing analysis of wild and cultivated A. lancea samples from multiple provinces in China, we revealed that the genetic divergence into Maoshan-Dabie Mountains group (MA) and Qinling-Taihang Mountains group (SA) was occurred along altitudinal and climatic gradients, but the chemotype was not solely genetically determined. Interestingly, both MA and SA genotypes in the MSA-favorable or HBA-conducive soil could develop into the MSA or the HBA chemotype, respectively, indicating a role of the soil microbiome. Critically, specific rhizosphere microbiomes were indicated as key mediators-core in this process, including Streptomyces in MSA formation and Paenibacillus in HBA formation. Shared endophytic core genera, such as Rhodococcus, Ralstonia, Sphingomonas, and Bradyrhizobium, further contributed to this divergence through species-level functional variation. Using piecewise structural equation modeling, we further confirmed that altitude, climate, and soil properties directly or indirectly influenced the chemotype formation via genotype-microbiome interactions. Taken together, this study highlights the central role of soil and microbes in the chemotype differentiation of A. lancea and provides new insights into its underlying mechanisms. The regulatory role of microbes in the production of volatile bioactive compounds offers a theoretical foundation for the microbial breeding strategies to improve medicinal quality and clinical efficacy.