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.