Collaboration of the symbiotic microbiome and host genome during the high altitude adaptation of chickens

The harsh environments of high-altitude habitats present formidable challenges for animal survival and reproduction. The adaptation of plateau endotherms to hypoxic and cold stresses has been studied for more than a century. However, the responses and contributions of the symbiotic microbiota to host adaptation remain unclear. Here, we conducted an integrated analysis of the gut and respiratory microbiomes of Tibetan chickens native to the high-altitudes of Lhasa and maintained for 20 years (approximately 20 generations) in low-altitude Beijing, as well as other high- and low-altitude breeds, to determine microbiota-host co-evolution in high-altitude adaptation. The results revealed that the respiratory microbial composition differed from that of the gut. The cecal microbiota was enriched in metabolic pathways, whereas the lung microbiota was more enriched in environmental information processing. Higher microbial diversity was observed in the ceca of chickens housed in Lhasa, whereas the lungs presented lower microbial diversity. Notably, consistent with the varying altitudes, the microbial communities in the ceca and lungs could be classified into distinct enterotypes and pulmotypes, respectively. The lung microbiome exhibited a more rapid environmental adaptation response to high-altitude environments, as 88 microbial genera were identified as signatures of high-altitude adaptation compared with only 7 in the ceca. Additionally, cecal Acetobacteroides was jointly regulated by the environmental conditions and host genetics, with higher abundance in the high-altitude chickens. FST analysis and mbQTL mapping identified NAT8L as a key gene under natural selection influencing Acetobacteroides colonization. Moreover, genotype-associated differences in metabolite levels indicate a potential link between NAT8L and Acetobacteroides, possibly through shared involvement in alanine, aspartate, and glutamate metabolism. These findings reveal a host gene-metabolism-microbiota axis that enhances energy efficiency, offering new perspectives for microbiota-host collaboration in high-altitude adaptation.