Dietary Imprinting of the Developing Microbiota: Implications for Healthy Aging
How the gut microbiome changes over the course of one's life has been a subject of intense investigation. Most of these studies have focused on the microbiomes of infants and the elderly because longer prospective studies are either difficult to perform or infeasible. These studies have shown that diet has an important role in the assemblage of our gut microbiota, which may have lasting consequences that determine the states of health or disease. A remarkable example of this comes from a study that tracked the microbiota of an individual baby over the first 2.5 years of life with a diary of diet and health status. The development of the gut microbiota was nonchaotic and nonrandom, building gradually over time but with discrete punctuations coinciding with changes in diet, antibiotics, or health. These punctuations were marked by abrupt shifts in abundance of particular microbes – perhaps the most notable shift in the microbial composition coming when the baby switched from breast milk to a full adult diet. In an extensive survey of the developing gut microbiome in individuals across cultures, Yatsunenko et al. identified microbial gene signatures that distinguished Malawian and Amerindian infants from infants in the USA based largely on the content of the mother's breastmilk and the native diet onto which the infant was weaned. For example, microbial genes for foraging host-derived glycans, such as exo-α-sialidase and α-fucosidase, were significantly overrepresented in Malawian and Amerindian infants, compared with infants in the USA, and decreased over time as the infants were transitioned to the native vegetable-based diet. Conversely, microbial expression of α-fucosidase increased over time in U.S. infants as they were transitioned from breast milk to a Western diet high in readily absorbed sugars. Therefore, the functional microbiomes acquired by these infants were very likely determined initially by the maternal factors early in life, then adapted to the native diet, the long-term consequences of which have yet to be determined. Many other studies have looked at the impact of breast-feeding versus formula-feeding on inflammation and allergies, and they have underscored the relationship between infant feeding and later-life disease outcomes. Studies by Carlisle et al. in mice and Schwartz et al. in humans analyzed the taxonomic and metatranscriptomic differences in microbiota to better understand the impact of breast-feeding versus formula-feeding on host–microbiome interactions. Whereas there appears to be an increase in Firmicutes in maternal-fed mice, and Proteobacteria and Bacteroides in formula-fed mice, the opposite was found in human infants. At the metatranscriptomic and metagenomic level, however, both studies revealed consistent and distinct differences in the microbiota of breast-fed and formula-fed individuals, where microbial genes related to oxidative stress, gut structural integrity, and immunity/defense genes in the host were highly represented in formula-fed hosts. These findings support the notion that the types of diet consumed early in life by individuals can profoundly affect the assemblage of gut microbial communities, but, ultimately, the functional profile of the microbial community determines the impact and long-term consequences in the host.
Whereas there are data to suggest that the healthy adult gut microbiome is relatively stable, that of the infant appears to be in flux. It now appears that the gut microbiome of elderly individuals may also be metastable. In a study of 178 individuals with an average age of 78 years old, Claesson et al. found significant interindividual differences in the gut microbiota, which they felt were related to the composition and diversity of the diet. In their study, the diet was primarily determined by the living arrangements, that is, whether in a free-living community setting or in long-term residential care. The microbiota of individuals in long-stay care were significantly less diverse than that of community dwellers, and the authors found that the differences in the respective microbiota significantly correlated with the measures of frailty, comorbidity, nutritional status, markers of inflammation, and with metabolites in fecal water. These data therefore supported the interrelationship between diet, microbiota, and health status, but particularly underscored the role for diet-driven microbiota alterations in varying rates of health decline upon aging. Together, the emerging evidence supports the notion that the diets consumed at different stages of life can greatly influence health status through their effects on the gut microbiome, and in turn impact on the host. From these data, a compelling case for dietary intervention, aimed at reshaping the gut microbiome, can be made to restore intestinal, metabolic, and immune homeostasis.