The human body comprises of micro-ecosystem made up of trillions of microbes (i.e. bacteria, archaea, fungi, protists and viruses). The total microbial gene content, which is referred to as the human microbiome, is fundamental to human physiology and immunity. There exists an intricate relationship between the surrounding microbial world (i.e. the environment) and the endogenous human microbiome, mediated by the immune system. Disrupting this relationship can a profound effect on human health and disease. Understanding how microbial exposure influences immune response and the feedback on endogenous microbial metabolic activity could have profound implications for the development of novel microbial therapeutics. The term 'microbial exposure' is used generally to refer to exogenous environmental microbial interaction, while 'exposome' accounts for both the environmental exposures and the impact of lifestyle-associated microbial impacts, such as diet influences on endogenous microbial metabolism. In this review, we focus on how environment and lifestyle-associated microbial exposures shape the human immune system and microbiome, and how the resulting changes can shape human health, especially during critical developmental windows, that is prenatal, postnatal and adult. We conclude this review by proposing approaches to characterize the microbial exposome so as to accelerate the development of a precision microbial therapeutics for both practical and clinical intervention.