It has been shown that the intestinal microbiota changes with aging. Accompanying this age-associated alteration, low levels of chronic inflammation and reduced levels of pathogen-specific immunity, known as inflammaging, are observed. A lack of oral tolerance has also been noted during the early stage of aging which may cause inflammaging and the subsequent induction of low levels of gastrointestinal immune responses. Since the alteration of intestinal microbiota and diminished immunity are closely associated in the elderly, it may be necessary to rejuvenate aged intestinal microbiota and maintain it in order to prevent respiratory infection, which exhibits high mortality in the elderly, although it could be a difficult task at present. Since the upper respiratory immune system is less influenced by aging and intestinal microbiota changes, newly developed innovative nasal vaccine approaches may overcome reduced levels of mucosal and systemic immunity. Such strategies may lead to the extension of healthy life expectancy which would also contribute to the establishment of a society with sustainable development goals.

During and immediately after birth, mammals are exposed to bacteria of maternal and environmental origins, some of which colonize the intestinal lumen to form the early-phase intestinal microbiota. The immature intestinal microbiota during infancy is unstable and susceptible to various environmental factors. Many epidemiological studies have shown that delivery by cesarean section and antibiotic exposure affect the gut microbiota early in life, possibly predisposing the host animals to immune allergic diseases in adulthood. However, the mechanism linking the early microbiota and disease susceptibility remains unclear. A growing body of evidence indicates that intestinal microbiota-dependent immune imprinting occurs only during a specific period in infancy, and that lack of immune imprinting during this “window of opportunity" may lead to immune allergic diseases after weaning. Therefore, expectations are high that research into a methodology for the normalization of the intestinal microbiota during infancy will lead to the prevention of the onset of future immune allergic diseases.