The evolution of the host microbiome as an ecosystem on a leash

Abstract

The human body carries vast communities of microbes that provide many benefits. Our microbiome is complex and challenging to understand, but evolutionary theory provides a universal framework with which to analyse its biology and health impacts. Here we argue that to understand a given microbiome feature, such as colonization resistance, host nutrition or immune development, we must consider how hosts and symbionts evolve. Symbionts commonly evolve to compete within the host ecosystem, while hosts evolve to keep the ecosystem on a leash. We suggest that the health benefits of the microbiome should be understood, and studied, as an interplay between microbial competition and host control.

Box 2 Figure. Simulation of bacterial growth on host epithelium

Left, brown bacterial cells (strain B) have a 1% growth rate advantage over blue bacterial cells (strain A). Even with a modest growth rate advantage, strain B succeeds and strain A is outcompeted in a few days. Right, plots of thirty independent simulations of bacterial competition. Development of biomass of strain B (brown dashed) and A (blue) with growth rate advantages for strain B of 1%, 10%, and 100% and environmental capacity K. The thick lines are mean values. From ref. .

Figure 1. Convergent evolution of the host epithelial interface with the microbiota

a–c, The study of the mammalian microbiota is most developed but it is becoming clear that diverse animals (a, b) and plants (c) possess epithelial surfaces where a complex microbiota can grow. In these systems, the host releases nutrients, antimicrobials, and a slimy matrix of mucus or mucilage, which are all thought to help control the microbiota (host control). In return, the symbionts may provide nutrients and protection from pathogens through antimicrobial (Antimicro.) release and other mechanisms^,,,,. Notably, the common ancestor of plants and animals is a single-cell organism, which means that these adaptations have evolved convergently after multicellularity evolved in the two lineages. This convergence is an indicator of common evolutionary principles across diverse systems. a, Human large intestine. The host secretes glycoproteins (Glyco.), such as mucins, which certain microbes attach to and feed on. Large amounts of IgA are released, which may both help and harm symbionts by affecting adhesion. Defensins (antimicrobial peptides), acids and oxygen release also shape the symbiotic community. b, Coral epidermis. Corals have many of the same features as the mammalian intestine, including mucins that contain microbes, acids and oxygen. Whether antimicrobial peptides (AMPs) are released from the epidermis is not yet clear but the innate immune system shapes the epithelial microbiota in the coral-relative Hydra. c, Plant-root epidermis. Plants release mucilage that contains arabinogalactan (AG) proteins, which appear to be functionally similar to mucins, and sugars and other carbon sources in large quantities, which all provide nutrients for the root microbiota^, The release of oxygen, antimicrobials, and particularly organic acids, also shapes the microbiota of the rhizosphere^,. Icons made by Freepick from http://www.flaticon.com/ (a) and https://www.vecteezy.com/ (b, c).

Figure 2. Models of host–microbiome interaction

Black arrows represent ecological interactions within the microbiota, red arrows indicate mechanisms of control. a, Ecosystem on a leash. When host species interact with a diverse but beneficial microbiota, as occurs in mammals, evolutionary theory predicts that the microbial functions will centre on persistence in the microbiome ecosystem, while the host will attempt to control the microbiota, hence the ‘leash’ (Boxes 1 and 2). Image courtesy of A. D. Wilson. b, Host control. For interactions involving few microbial strains, ecological complexity is reduced and microbes are primarily shaped by the host environment. Natural selection on the host, therefore, can result in strong shaping and control of the phenotypes of beneficial microbes. The bobtail squid has a specialized light organ, which controls both the access and light production of the symbiotic bacteria that grow inside^,. One hypothesis is that host enzymes generate bacteriocidal compounds from substrates that become available if the bacteria do not perform the light-producing reaction. Photo of Euprymna scolopes, the Hawaiian bobtailed squid, by M. McFall-Ngai, PBRC, University of Hawaii-Manoa, published with permission. c, Symbiont control. Low microbial diversity also increases the potential for microbes to affect global host traits—including survival, reproduction and behaviour—and receive a fitness benefit from doing so (Box 2). This may select for adaptations that function to increase host fitness, such as enzymes that feed the host, but slow microbial growth. However, this can also enable symbiont manipulation of the host, such as for ‘zombie’ fungi, infection with which causes ants to move to a position ideal for fungal development. Photo of Ophiocordyceps unilateralis and ant by D. Hughes, Penn. State, published with permission. d, Open ecosystem. A host carries a complex ecosystem without evolved control mechanisms beyond compartmentalization. This is most likely to occur if the microbiota are rarely either a threat or a benefit. Pitcher plants use pools of water to kill and digest prey. Although these plants regulate the pool by releasing enzymes and acids to promote digestion, there is currently little evidence that the plants have dedicated mechanisms to regulate the pool microbiota. Image adapted from P. J. Ding used under Creative Commons Licence.