Genome-resolved analysis of bile acid-metabolizing microbiota in Tibetan antelope (Pantholops hodgsonii)

The Tibetan antelope (Pantholops hodgsonii), an iconic species endemic to the Qinghai-Tibet Plateau, thrives at altitudes of 4,500–5,000 m under conditions of extreme hypoxia, cold, and limited nutrition. As a critical mediator of host physiology, the gut microbiome may play a key role in supporting these adaptations. This study presents the first genome-centric investigation of bile acid (BA) metabolism in the gut microbiome of the Tibetan antelope, unveiling unique microbial pathways that potentially facilitate survival in harsh environments. Comparative analysis of metagenome-assembled genomes revealed that the antelope’s BA-metabolizing microbiota is taxonomically distinct from that of other Caprinae species and humans, with only two of the top ten BA-producing genera shared across groups. Importantly, individuals infected with Blastocystis exhibited marked differences in BA-related KEGG ortholog (KO) profiles compared to uninfected counterparts. Our findings highlight that the proportion of bile salt hydrolase (K01442) genes in the gut microbiota of Tibetan antelopes is higher than that in other Caprinae species and humans. Among them, the genus Alistipes carries the highest proportion of K01442 in the Tibetan antelope’s gut microbiota. Additionally, infection-associated KO gene shifts were observed, suggesting a microbial contribution to the Tibetan antelope’s remarkable physiological resilience. In Tibetan antelopes, Alistipes was the dominant genus associated with bile acid synthesis. While bile acid synthesis KO distributions were broadly similar across species, K01442 higher proportion than other in Tibetan antelope gut microbiomes. Furthermore, Blastocystis infection altered three key bile acid synthesis KOs and induced distinct shifts in gut microbiome composition.