Because the development of the microbiota is affected by so many clinical factors, including mode of delivery, feeding mechanism, antibiotic or probiotic treatment, and contact with parents, siblings, and hospital staff, the clinical implications of this recently published link between microbiota and the nervous system pose some intriguing questions (Figure 2). For example, what effect does early use of antibiotics have on neonates, especially during critical periods such as the first year of life? Antibiotics are often used in newborns admitted to the intensive care unit; however, routine antibiotic use does not have a statistically significant effect on the incidence of sepsis or mortality with regard to newborns.41 Cotton et al42 found that prolonged antibiotic use in preterm neonates can be correlated with a higher incidence of necrotizing enterocolitis. If antibiotic use alters the composition and function of gut microbiota long after the administration of antibiotics has stopped, should we advocate for the repopulation of gut microbiota after antibiotic use or after gastrointestinal diseases, and can this play any role in brain plasticity? Are probiotics good candidates for this sort of treatment? Studies in adults have shown that probiotic use can decrease the incidence of diarrhea, stimulate humoral and cellular immunity, and decrease production of unfavorable metabolites, after antibiotic use.43 Can these findings be extended to neonates, even preterm neonates? What other factors can change the microbiome? Besides the known benefits of reducing the number of apneas and stabilizing oxygen saturation, respiration, and heart rate, does skin-to-skin contact (“kangaroo care”) provide a “natural” source of maternal microbes to repopulate neonatal gut microbiota? Breast milk favors the growth of certain commensal bacterial species and offers approximately 109 live bacteria per liter.44 Could we use breast milk or a changing diet to modulate the microbiome and therefore protect against diseases and protect brain development? Could early breastfeeding prevent diseases through mechanisms related to microbiota changes? When and for how long do these factors exert their effects? Early life exposures may be necessary, especially when considering the possibility of epigenetic programming mechanisms. As developing tissues are exposed to different bacterial species, epigenetics may come into play by influencing gene expression, such as DNA methylation and histone modifications.45 Is there a further epigenetic programming mechanism that changes the human microbiome? Do changes in the composition of commensal bacteria (eg, decreases in Bacillus fragilis and its specific bacterial antigens) trigger or exacerbate future central nervous system demyelinating diseases? What effects do changing gut microbiota have on other host diseases, such as autism or obesity? These questions and others need to be explored and answered.