BACKGROUND: The contribution of gut microbiota to human high-altitude adaptation remains inadequately understood.
METHODS: Here a comparative analysis of gut microbiota was conducted between healthy individuals living at sea level and high altitude using deep whole-metagenome shotgun sequencing, to investigate the adaptive mechanisms of gut microbiota in plateau inhabitants.
RESULTS: The results showed the gut bacteriomes in high-altitude individuals exhibited greater within-sample diversity and significant alterations in both bacterial compositional and functional profiles when compared to those of sea-level individuals, indicating the potential selection of unique bacteria associated with high-altitude environments. The strain-level investigation revealed enrichment of Collinsella aerofaciens and Akkermansia muciniphila in high-altitude populations. The characteristics of gut virome and gut mycobiome were also investigated. Compared to sea-level subjects, high-altitude subjects exhibited a greater diversity in their gut virome, with an increased number of viral operational taxonomic units (vOTUs) and unique annotated genes. Finally, correlation analyses revealed 819 significant correlations between 42 bacterial species and 375 vOTUs, while no significant correlations were observed between bacteria and fungi or between fungi and viruses.
CONCLUSIONS: The findings have significantly contributed to an enhanced comprehension of the mechanisms underlying the high-altitude geographic adaptation of the human gut microbiota.

Low oxygen levels and extremely cold weather in high-altitude environments requires more energy intake to maintain body temperature in animals. However, little is known about the characteristics of cecal and ileac microbiota in Tibetan chicken and how the high and low altitude environments affect the gut microbiota communities in Tibetan chicken. In the present study, In the present study, Tibetan chickens (Group HA, 3572 m, 578.5 Pa) and their introduced flatland counterparts (Group LA, 580 m, 894.6 Pa) in the cecum and ileum to identify the possible bacterial species that are helpful for their host in environmental adaption. High-throughput sequencing was used to sequence the V3 to V4 hypervariable regions of the bacterial 16S rRNA gene. By comparing the gut microbial diversity of HA chicken with that of LA, the results indicated that the microbial diversity of the cecum and ileum in group HA was significantly lower (P < 0.05) than those in group LA. The cecum microbiome maintained higher population diversity and richness than the ileum (P < 0.05). Four phyla Firmicutes, Bacterioidetes, Actinobacteria, and Proteobacteria were dominant in two groups. Interestingly, there were significant differences in abundance ratio among the four groups (P < 0.05). The predominant bacteria in HA and LA ileum belong to Proteobacteria and Firmicutes, whereas in cecum, Bacterioidetes and Actinobacteria were predominant in both groups (P < 0.05). Correlation analysis showed that Sporosarcina, Enterococcus, and Lactococcus were strongly related to air pressure, and Peptoclostridium and Ruminococcaceae_UCG-014 are related to altitude and gut microbiota of LA group was influenced by altitude, while HA group affected by air pressure. Meanwhile, the Ruminococcus-torques-group was negatively correlated with the relative abundance of Paenibacillus, and positive correlated with those of other microorganisms. Furthermore, HA has higher abundance of microbiota involved in energy and glycan biosynthesis metabolism pathway, while LA has higher abundance of microbiota involved in membrane transport, signal transduction, and xenobiotics biodegradation and metabolism. Generally, our results suggested that the composition and diversity of gut microbes changed after Tibetan chickens were introduced to the plain. Tibetan chicken may adapt to new environment via reshaping the gut microbiota. Gut microbes may contribute to the host adaption to high altitude environments by increasing host energy and glycan biosynthesis.

High-altitude inhospitable environments impose a formidable life challenge for the local animals. Training and exposure to high-altitude environments produce both distinct physiological and phenotypic characteristics. The mitochondrion, an organelle crucial for the energy production, plays an important role in hypoxia adaptation. In this study, we investigated the mitochondrial DNA (mtDNA) polymorphism and copy number variation between the population pairs from distinct altitudes across the multi-species. Higher mitochondrial DNA control region\'s genetic diversity is conspicuous in high-altitude animals versus low-altitude relatives. We also found an accordant decrease of mtDNA copy number in most of the tissues from high-altitude animals. Compared to mammals, chickens have significantly distinct mitogenomic characteristics, and more significant changes in the skeletal muscle mtDNA copy number between high- and low-altitude individuals. Our study catches a snapshot of the biological similarities and differences in the mitochondrial high-altitude acclimation across the species.

Over millions of years, vertebrate species populated vast environments spanning the globe. Among the most challenging habitats encountered were those with limited availability of oxygen, yet many animal and human populations inhabit and perform life cycle functions and/or daily activities in varying degrees of hypoxia today. Of particular interest are species that inhabit high-altitude niches, which experience chronic hypobaric hypoxia throughout their lives. Physiological and molecular aspects of adaptation to hypoxia have long been the focus of high-altitude populations and, within the past decade, genomic information has become increasingly accessible. These data provide an opportunity to search for common genetic signatures of selection across uniquely informative populations and thereby augment our understanding of the mechanisms underlying adaptations to hypoxia. In this review, we synthesize the available genomic findings across hypoxia-tolerant species to provide a comprehensive view of putatively hypoxia-adaptive genes and pathways. In many cases, adaptive signatures across species converge on the same genetic pathways or on genes themselves [i.e., the hypoxia inducible factor (HIF) pathway). However, specific variants thought to underlie function are distinct between species and populations, and, in most cases, the precise functional role of these genomic differences remains unknown. Efforts to standardize these findings and explore relationships between genotype and phenotype will provide important clues into the evolutionary and mechanistic bases of physiological adaptations to environmental hypoxia.