An ecological and evolutionary perspective on human-microbe mutualism and disease

Abstract

The microbial communities of humans are characteristic and complex mixtures of microorganisms that have co-evolved with their human hosts. The species that make up these communities vary between hosts as a result of restricted migration of microorganisms between hosts and strong ecological interactions within hosts, as well as host variability in terms of diet, genotype and colonization history. The shared evolutionary fate of humans and their symbiotic bacteria has selected for mutualistic interactions that are essential for human health, and ecological or genetic changes that uncouple this shared fate can result in disease. In this way, looking to ecological and evolutionary principles might provide new strategies for restoring and maintaining human health.

Figure 1 |. Site-specific distributions of bacterial phyla in healthy humans.

The area of the chart for each site represents the average number of distinct phylotypes (approximate species-level taxa, based on 16S rRNA gene-sequence analysis) per individual. (The mean number of phylotypes per individual is shown in parentheses; 3–11 individuals were studied per habitat.) The coloured wedges represent the proportion of phylotypes belonging to different phyla. More than 50 bacteria phyla exist, but human microbial communities are overwhelmingly dominated by the 4 that are shown. The relative abundance of these phyla at most sites tends to be consistent across individuals: for example, in almost all humans studied so far, Bacteroidetes and Firmicutes predominate in the colon. By contrast, the composition of the vaginal microbiota is more variable; most women have a preponderance of Firmicutes with few other representatives, whereas a minority of women have a preponderance of Actinobacteria with few other representatives. An estimated 20–80% of human-associated phylotypes (depending on habitat) are thought to have eluded cultivation so far. Data taken from refs –.

Figure 2 |. Patterns of human-associated microbial diversity.

a, Lineage-by-distance analysis of 16S rRNA gene-sequence data from human microbial communities in specific habitats. The x axis shows the percentage difference threshold (Olsen correction), over 1,241 unambiguously aligned positions of near full-length 16S rRNA gene sequences, for delineating separate lineages. The y axis shows the number of distinct lineages that exist at the distance threshold. If speciation and extinction occur with constant probabilities as 16S rRNA gene sequences diverge, this would result in an exponentially increasing number of lineages with diminishing evolutionary distances between them (a straight line on a semi logarithmic plot). Such a pattern seems to hold from the phylum level (largest distances between lineages) to approximately the species level. However, relative to this trend, all sites have an excess of recently diverged lineages. The excess lineages accumulate in the range of 16S rRNA gene divergence that is typically associated with species and strains. The inset depicts a portion of the same data at a larger scale. Samples were taken from 3–11 individuals, depending on the site. Data taken from refs –. b, When displayed as a dendrogram, 16S rRNA gene-based patterns of microbial diversity in soil and aquatic environments generally resemble the tree shape on the left, with new branches arising at all distances from the root. Patterns of diversity in vertebrate-associated communities resemble the tree shape on the right, with few branches arising close to the root and many branches arising close to the branch tips.

Figure 3 |. Relationships between bacterial 16S rRNA gene sequences from the intestinal microbiota of animals.

A set of aligned, high-quality, full-length sequences was obtained from Greengenes. Sequences derived from one human stool sample and caecal samples from one mouse family were chosen to obtain approximately the same number of sequences as obtained from multiple studies of the bovine rumen and pig caecum and colon (range 617–748 sequences per host species). a, A neighbour-joining tree was created from 1,241 unambiguously aligned positions in all 2,735 sequences, with selected taxa indicated. Mollicutes, Lactobacillaceae and Clostridium clusters IV and XIVa are within the Firmicutes. b, Host-specific trees were created with the same topology as the entire tree, shown in part a, but they depict only the sequences derived from the indicated host species. Branches shared with at least one other host species are shown in black, and branches specific to a single species are coloured. The same phyla and classes predominate in these animals (evident from the overlapping tree topologies and shared branches), although their relative abundances vary. By contrast, most genera and many families are specific to a single host species (coloured branches).

Figure 4 |. Adaptive landscapes.

The plane is a conceptual representation of the multidimensional phenotypes that are available to a microorganism. The height of the surface above the plane represents the fitness of the corresponding phenotypes in a given ecological context, including biotic and abiotic components of the environment. In a given environment (context A, upper panel), for mutations that have a small effect, a phenotype (circle) under natural selection will tend to evolve along the steepest path uphill towards higher fitness (solid arrow), eventually moving the mean phenotype of a population to a local fitness maximum. Mutations that have a large effect, such as horizontal gene transfer, can shift a phenotype to the slope of a different fitness peak (dashed arrow). This can markedly alter the outcome for the host; for example, it can result in pathogenesis instead of mutualism. The valley separating the peaks represents phenotypes of low fitness, such as those that are likely to elicit an immune response but lack the adaptations necessary to survive it. For a given phenotype, a change in context (for example, a change in host diet, alterations in coexisting microbial populations, or transfer to a different host or host species; context B, lower panel) can have subtle or marked effects on fitness. A phenotype near a fitness peak in context A might be in a valley of low fitness in context B. If the microorganism survives, the subsequent course of evolution might depend on the direction of phenotypic change caused by the next mutation.