Analysis of the Gut Microbiome of Rural and Urban Healthy Indians Living in Sea Level and High Altitude Areas - Scientific Reports

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• Highest microbial diversity was detected in the study subjects living in rural low altitude areas. Furthermore, compared to the gut microbiome of Leh subjects, people living in the Ballabhgarh region harbor large number of genes that are linked with the membrane transport, carbohydrate metabolism, lipid metabolism, ion-channels and signal transduction pathways (Fig. 11). Most importantly, the gut microbiomes from Ballabhgarh were predicted to have a high abundance of genes belonging to several xenobiotic degradation pathways. This could be the reflection of the high exposure of these individuals to industrial/agricultural chemicals like fertilizers, pesticides as compared to the subjects from the high-altitude regions of Leh, which is relatively remote from industrialization and agricultural pollution. Furthermore, the subjects from Leh were observed to not only have the least abundance of Proteobacteria, but also a significantly high abundance of bacteria like Faecalibacterium and Lachnospiraceae that encode anti-inflammatory functions. Functions linked with the vitamin biosynthesis, energy metabolism and anti-inflammatory pathways like Zeatin biosynthesis are significantly high in the gut microbiome of Leh subjects.

• hese observations emphasize the importance of numerous common environmental exposures in shaping gut microbial ecology. Moreover, the similarity in overall pattern of the community structure suggest that despite the large influence of cultural factors, the similarity among members of each population across the three populations studied are remarkable.

• The minimal representation of Proteobacteria in the gut of Leh population is very attractive and representing a potential source of healthy gut microbiota in fecal microbiome transplantation-based therapeutics. Although all three groups had healthy individuals, yet rural community from low altitude areas had a unique microbiome characterized not only by a higher diversity, but also a higher degree of homogeneity within the same cohort. The insights from the current findings thus have high translational value, considering the identification of ideal subjects as donor for fecal microbiome transplantation.