Getting to know our microbial friends by dropping into their neighbourhood

Imagine an interstellar explorer arriving in orbit around Earth, and deciding to examine the nature of its inhabitants. While much can be discerned just by measuring their general distribution and net activities at a distance, the explorer desires to get closer to the surface to better understand the diversity of organisms present and how their individual actions combine to produce global effects. Ideally, to walk among the inhabitants and discover whether the same kind of organism may have a different behaviour when its surroundings are different provides a deeper understanding of each inhabitants’ predictable and, perhaps, unpredictable roles in the environment. A similar situation is faced by microbial ecologists, who have been, until recently, stuck in their orbiting spacecraft, unable to land and wander among, or perceive interactions within, an environment’s microbial community. But what if microbial ecologists could observe their subjects as easily as they can comprehend the citizens of a city during a walk around its crowded streets? How close are microbiologists to realizing the dream of such a walk, and what will they discover once they can? These questions are the motivation behind this essay. At the end of the 19th century, two great traditions in microbiology were developing. One was pioneered by Robert Koch and Louis Pasteur (Blevins and Bronze, 2010), who devised methods to grow and study bacteria in pure culture, leading to a rapid advance in understanding disease mechanisms and launching the field of biotechnology. The other tradition was inspired by Sergei Winogradsky (Dworkin, 2012), who sought to comprehend the activities of microorganisms by examining their growth and chemistry within complex communities, such as those in soil or sediment, that we would now call environmental microbiomes. While it was assumed that these communities consisted of many species of bacteria and other microbes, only a fraction of these microorganisms could be grown and studied individually in culture. Even those that were cultured often failed to exhibit their key ecological activities when isolated from the whole microbiome. This latter observation drove microbiologists to find ways to examine microbial communities in their intact, native state. Such efforts initially were limited to measuring the net activity and products of the microbiome, and it was clear that any deeper understanding would require a knowledge of not only the membership of the community, but also each member’s individual metabolic and ecological contributions as both a function of time (e.g. day/night, summer/winter) and its proximity to others (Cordero and Polz, 2014). The development of ribosomal DNA (e.g. 16S) amplicon sequencing in the 1990s provided a means by which to catalogue the surprising number and abundance of both culturable and non-cultured species that are present in many natural environments. Similarly, during the last decade, metagenome-assembled genome (MAG) sequencing, coupled with annotation of the sample’s total gene pool, provided a roadmap of the functional potential of the community as a whole, and even of its individual species. One resulting discovery was the surprising reproducibility of the species membership within microbial communities found in similar environments. While there were certainly ‘tourists’ that intermittently passed through the habitat, generally there was also an environmentally determined ‘resident’ microbiota that was predictably present. In the case of the mammalian digestive tract, the literature became replete with evidence that the members in the resident gut microbiota were not only predictable, but their presence was also demonstrably beneficial to the host’s normal development and health (Rook et al., 2017). In spite of this increasing evidence, many studies continue to refer to these important microbial partners as ‘commensal’, a carry-over from an earlier time when the gut microbiota was believed to be of little consequence to Received 7 October, 2020; accepted 8 October, 2020. *For correspondence, E-mail eruby@hawaii.edu; Tel. 808-539-7309; Fax 808-599-4817.