Abstract
Humans are virtually identical in their genetic makeup, yet the small differences in our DNA give rise to tremendous phenotypic diversity across the human population. By contrast, the metagenome of the human microbiome—the total DNA content of microbes inhabiting our bodies—is quite a bit more variable, with only a third of its constituent genes found in a majority of healthy individuals. Understanding this variability in the “healthy microbiome” has thus been a major challenge in microbiome research, dating back at least to the 1960s, continuing through the Human Microbiome Project and beyond. Cataloguing the necessary and sufficient sets of microbiome features that support health, and the normal ranges of these features in healthy populations, is an essential first step to identifying and correcting microbial configurations that are implicated in disease. Toward this goal, several population-scale studies have documented the ranges and diversity of both taxonomic compositions and functional potentials normally observed in the microbiomes of healthy populations, along with possible driving factors such as geography, diet, and lifestyle. Here, we review several definitions of a ‘healthy microbiome’ that have emerged, the current understanding of the ranges of healthy microbial diversity, and gaps such as the characterization of molecular function and the development of ecological therapies to be addressed in the future.
Highlights
Humans have co-evolved with the trillions of microbes that inhabit our bodies and that create complex, body– habitat-specific, adaptive ecosystems that are finely attuned to relentlessly changing host physiology
Dysbioses in the microbiome have been associated with numerous diseases, including inflammatory bowel disease, multiple sclerosis, diabetes, allergies, asthma, autism, and cancer [1,2,3,4,5]
An understanding of the properties of a healthy microbiome, and the many different microbial ecologies that are encountered in the absence of overt disease, is a necessary first step to identifying and correcting microbial configurations that are implicated in disease
Summary
Humans have co-evolved with the trillions of microbes that inhabit our bodies and that create complex, body– habitat-specific, adaptive ecosystems that are finely attuned to relentlessly changing host physiology. Other prevalent but lower-abundance bacteria included members of the genera Bifidobacterium, Eubacterium, Lactobacillus, and Streptococcus, as well as facultative anaerobes such as Escherichia It was already suspected at this time that a large number of human-associated microbial species remained undiscovered, with one study estimating the simultaneous presence of some 400 microbial species in a healthy colon [16, 17]. Studies using FISH targeting the 16S ribosomal RNA gene suggested that at least two-thirds of the gut bacteria in a western European cohort could be attributed to a set of six groups at approximately the species/genus level: two Bacteroides, two Clostridium, Streptococcus/Lactococcus, and Eubacterium rectale [19] This has since proved to be optimistic and, even at the time, large variability was observed in the abundances of these groups between samples (standard deviations of ~60–80 % of their means) [19]. The number of population-scale healthy microbiomes surveyed in the gut and other body sites exceeds 2000 individuals spanning multiple continents
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