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Although our knowledge of the disease impacts of pathogens is well established, the role of complex nonpathogenic microbiota communities in sustaining health or promoting disease is a rapidly expanding research area. The microbiota, the complement of microbial cells coinhabiting in an individual, exceeds at least 10-fold the number of human origin cells. Furthermore, the microbiome, the gene collective of this resident microbial community, exceeds by at least 100 times the complement of genes present in the human nuclear genome. Many studies now show that in healthy individuals, the immune system is responsible for maintaining a controlled homeostasis with the normal microbiome. However, when these bacterial communities become skewed toward fewer species with pro-inflammatory properties, this homeostasis is disrupted. Under these conditions, known as dysbiosis, highly damaging inflammatory responses can occur. This entry provides an overview of the human microbiome across the life span, demonstrates how shifts in its composition contribute to the development of disease, and explores the emerging science on the microbiome and how it might be used to create future therapies.

The Gastrointestinal Tract Microbiome Over the Life Span

With over 200 square meters of mucosal surface area and a nutrient rich environment, the gastrointestinal tract (GIT) hosts the majority of human microbiota. Absorption in the distal gut results in approximately 10% of the metabolites in the host systemic blood flow being of bacterial origin. Advances in next generation DNA sequencing technology now permit the characterization of entire microbiomes without the need for bacterial culturing. As a result, the microbiome has become one of the fastest growing areas of biomedical research.

Multiple studies suggest that long-term diet is important in shaping GIT microbial communities. Comparisons of children from Europe on a typical Western diet, high in animal protein and fat, with children from Burkina Faso in Africa on a low animal protein and high-carbohydrate diet found that Bacteroides species were higher in Europeans and the Prevotella species predominated in African children. Another study also found that animal fat and high protein versus carbohydrate-rich diets correlated with the Bacteroides and Prevotella communities, respectively. In the same study, controlled feeding of 10 participants with high-fat, low-fiber versus low-fat, high-fiber diets produced detectable changes in their microbiome within 24 hours. However, overall individuals’ microbiomes remained stable for the duration of the 10-day study, suggesting that long-term rather than transient dietary trends determine the ecological structure of the gut microbial communities.

Other factors also influence microbiome composition over the life span of an individual. The neonatal intestine is nearly sterile at birth and is shaped by a number of external factors including the mode of delivery, breastfeeding and diet of the mother, and exposure to environmental toxicants. Infants delivered vaginally have microbial communities most similar to that of the mother’s vagina, whereas the microbiota from neonates born by Caesarean section more closely resembles the mother’s skin bacteria. Low-bacterial diversity characterizes the microbiomes of very low birth weight infants who develop neonatal sepsis.

The hygiene hypothesis suggests that the rapidly changing human lifestyle throughout the Western world has resulted in predisposition to multiple diseases due to imbalances in immune-microbiota coupling. Dramatic changes since the mid-1960s in widespread antibiotic use, improved hygiene, and higher fat diets are all potential contributing factors. Several studies suggest that dysbiosis of the microbiome early in life (which can be caused by very intensive and frequent antibiotic treatments) is associated with later life allergic sensitivity and immune-disorders including atopic eczema, necrotizing enterocolitis, and allergies.

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