Modern civilization is faced with a progressive increase in immune-mediated or inflammatory health problems such as allergic disease, autoimmune disorders, and obesity. An extended version of the hygiene hypothesis has been introduced to emphasize the intimate interrelationship among diet, the immune system, microbiome, and origins of human disease: the modern infant, particularly when delivered by cesarean section and without the recommended exclusive breastfeeding, may lack sufficient stimulation of the mucosal immune system to generate a tolerogenic immune milieu and instead be prone to develop chronic inflammatory conditions. These deviations may take the form of allergic or autoimmune disease, or predispose the child to higher weight gain and obesity. Moreover, evidence supports the role of first microbial contacts in promoting and maintaining a balanced immune response in early life and recent findings suggest that microbial contact begins prior to birth and is shaped by the maternal microbiota. Maternal microbiota may prove to be a safe and effective target for interventions decreasing the risk of allergic and noncommunicable diseases in future generations. These results support the hypothesis that targeting early interaction with microbes might offer an applicable strategy to prevent disease.