Studies have reported short term exposure to HA causes coagulation activation64,65 . Some species of Fusobacterium are known to induce platelet aggregation and portal vein thrombosis66,67,68 . The source of bacteraemia in these patients is not always evident. In the present study sudden appearance of Fusobacterium at H3 raises alarm suggesting thereby in cases of Fusobacterium bacteraemia of unclear aetiology, portal vein thrombosis should be ruled out at HA considering conditions like low temperature & oxygen pressure, humidity and high radiations etc67 . Fusobacterium abundance was positively correlated with LDL cholesterol and total cholesterol69 .
Further, we applied MIDAS for in depth analysis of stool metagenome at different heights and used rare SNPs to track upto strain level abundance to reveal extensive structure and dynamics to elucidate the role of altered gut microbioata in human health and diseases at different altitudes. The approach revealed Prevotella copri 61740 as the most abundant at HA. With that the door is opened up for further research to understand the role of Prevotella copri 61740 in the pathophysiology of HA diseases.
It is surprising and interesting to note that human gut microbiomes are functionally stable with very little variance in abundance or gene families as ”variables”. At the same time the relative abundance of host biological pathways is less variable than the relative abundances of microbial phyla in the same metagenome70,71 . Being the signature of health and disease, strong selection of microbes encodes functions necessary for adaptation to the gut environment indicating the correlation between the two. Thus, implying that human gut microbiota is phylogenetically same, doing similar work but when exposed to extreme conditions, plays differently, demonstrating a natural phenomenon for healing and tailoring therapies. Therefore, in the present study along with knowing composition of the microbial community, DNA sequencing for functional screening using metagenomic approach, was matched with known functional gene sequences. Identifying the genes involved in specific metabolic pathways, could predict functional capabilities, but without messenger RNA, protein and metabolite profiling, these were still predictions. We found significant microbiome alterations that are consistent with well-known side- effects of altitude conditions. The abundances of the predicted pathways emerging as significantly differentiating between four heights, appear to have a pattern of distinct functional divergence that grossly corresponds to environmental conditions. It is reported that the anaerobic environment of gut increases the tolerance capacity to oxidative stress and thus leads to microbial dysbiosis43 . The significant presence of other bacteria including Roseburia inulinivorans, Faecalibacterium prausnitzii, Oscillibacter and Eubacterium eligens, Eubacterium rectale, Megamonas hypermegale and Prevotella copri which had a very distinctive and increasing appearance at all heights and contrary to the Bacteroides vulgatus, encode butyrate producing functions.
It is suggested that Prevotella  is a beneficial bacteria as it is associated with a plant-rich diet, but at the same time due to its high species and strain genetic diversity72,73 , some of its strains become clinically important pathobionts as they promote and are linked to chronic inflammatory conditions, as arthritis, periodontitis, metabolic & cardiovascular disorders and systemic & mucosal T-cell activation in untreated HIV infection74,75 . Present study is indicative of Prevotella being one of the possible reasons for the gut inflammation at HA. Because of species heterogeneity, it needs to continue the in depth metagenomic analysis of the microbiota in inflammatory diseases so as to reveal its disease modulating role. Immunomodulatory role of Prevotella are reported with significant increase in serum IgA in Rheumatic arthritis which in turn may have implications for disease risk and outcomes76. Studies are being performed to delve into the basis of its associations with health and disease like effects on host metabolism, providing glucose tolerance in healthy individuals77 . Reports indicate association between degradation of antibiotics (Xenobiotic degradation) and the glycan metabolism with the abundance of Bacteriodetes31,78 mainly with abundance of Prevotella, but in the present study glycan metabolism was higher at H3 and lower at H2 and H4 which is converse with the hypothesis. This association between altered gut microbiota at extreme altitude and the functions demonstrate the effectiveness of functional information which could be a beneficial tool for studying disease mechanism rather than a taxonomical marker. It is therefore relevant and important considering the effects of Prevotella on host health under extreme climatic conditions at HA.