Trillions of microbes living in the gastrointestinal tract (GIT) of the human body finely tune homeostatic equilibrium in the GIT ecosystem and encode key functionalities that play crucial role in host metabolic functions, synthesis of macro- and micronutrients, xenobiotics metabolisms, development of innate and adaptive immune systems, tissue and organ developments and resistance against invasion of enteric pathogens. The microbial diversity and richness of GIT ecosystem varies greatly between individuals and over time. Extent of taxonomic and functional variations in GIT ecosystem is linked with dietary habit, pharmaceuticals usages, age, sex, body mass index, ethnicity, geography, altitude and civilization. Understanding a holistic picture of GIT microbiome of healthy people living across geography and identifying population specific 'keystone' taxa is of immense importance for identifying microbial species that may provide protection against chronic and metabolic diseases. Knowledge on geographic or ethnicity specific microbial signatures may also help us to understand the varied efficacy of different drugs and vaccines in different population. India is the home of more than 1.36 billion people belonging to 2000 human communities residing in well distinct geography. In the present review, we discuss the microbial signatures in health and diseases of the rural and urban Indians living in sea level and high altitude areas.