Commensal microbiota and host metabolic divergence are associated with the adaptation of Diploderma vela to spatially heterogeneous environments.

Heterogeneous environment adaptation is critical to understand the species evolution and response to climate change. However, how narrow-range species adapt to micro-geographic heterogeneity has been overlooked, and there is a lack of insights from metabolism and commensal microbiota. Here, we studied the environmental adaptation for 3 geographic populations (>40 km apart) of Diploderma vela, a lizard endemic to dry-hot valleys of the Hengduan Mountain Region. The climatic boundary caused a cooler, droughtier, and barren environment for northernmost population (RM) than the middle (QZK) and southernmost populations (FS). Correspondingly, significant divergences in liver and muscle metabolism and commensal microbiota were detected between RM and QZK or FS individuals, but not between QZK and FS individuals. Phospholipid composition, coenzyme level (i.e. pyridoxal and NAD ), and cholesterol metabolism (e.g. androgen and estriol synthesis) constituted the major metabolic difference between RM and QZK/FS groups. FS and QZK individuals kept abundant Proteobacteria and antifungal strains, while RM individuals maintained more Firmicutes and Bacteroidota. Strong associations existed between varied host metabolite and gut microbes. How were these interpopulation variations associated to the environment adaptation were discussed. These results provided some novel insights into the environmental adaptation and implicated the consequence of climate change on narrow-range species.