Cross-Domain and Viral Interactions in the Microbiome

Abstract

The importance of the microbiome to human health is increasingly recognized and has become a major focus of recent research. However, much of the work has focused on a few aspects, particularly the bacterial component of the microbiome, most frequently in the gastrointestinal tract. Yet humans and other animals can be colonized by a wide array of organisms spanning all domains of life, including bacteria and archaea, unicellular eukaryotes such as fungi, multicellular eukaryotes such as helminths, and viruses. As they share the same host niches, they can compete with, synergize with, and antagonize each other, with potential impacts on their host. Here, we discuss these major groups making up the human microbiome, with a focus on how they interact with each other and their multicellular host.

Keywords: archaea; bacteria; bacteriophage; cross-domain; fungi; helminths; microbiome; protozoa; virus.

FIG 1

Outline of the major components of the human microbiota, summarized across body sites, including the gastrointestinal tract, oral cavity, vaginal mucosa, and skin. (Top left) Bacteria are the most abundant and include members of the phyla Firmicutes (Clostridium, Lactobacillus, and Enterococcus), Bacteroidetes (Bacteroides and Prevotella), Proteobacteria (Escherichia and Acinetobacter), Actinobacteria (Bifidobacterium), and Verrucomicrobia (Akkermansia). (Top right) Based on metagenomics, human-associated fungi are significantly outnumbered by the bacteria; they are mainly members of the phylum Ascomycota (Candida, Saccharomyces, Aspergillus, and Malassezia), but some Basidiomycota are detectable. Humans may also be infected with nonfungal eukaryotic pathogens, which are not shown here. (Bottom right) Viruses in the human microbiota are primarily bacteriophage and likely outnumber the bacterial population by at least 10-fold. The virome is largely composed of Caudovirales (Siphoviridae, Myoviridae, and Podoviridae) and Microviridae, along with some eukaryotic host viruses. (Bottom left) Helminths are now typically absent from humans in high-income nations but still parasitize billions worldwide to various degrees of severity. They include trematodes (flatworms), nematodes (roundworms), and cestodes (tapeworms).

FIG 2

Outline of significant interactions between various human-associated bacteria and the fungus Candida albicans, ranging from cooperation to antagonism. abx, antibiotics.

FIG 3

Outline of key interactions between helminths, the bacterial gut microbiota, and the host immune system, including the “old friends” hypothesis that immunomodulatory influences of commensal bacteria and helminths can promote a tolerance phenotype and reduce the risk of immune-mediated autoimmune or allergic disorders. TNF-α, tumor necrosis factor alpha.

FIG 4

Outline of prominent virome-bacterium interactions that shape the community dynamics and function of the host microbiota.