Beyond Just Bacteria: Functional Biomes in the Gut Ecosystem Including Virome, Mycobiome, Archaeome and Helminths

Abstract

Gut microbiota refers to a complex network of microbes, which exerts a marked influence on the host's health. It is composed of bacteria, fungi, viruses, and helminths. Bacteria, or collectively, the bacteriome, comprises a significant proportion of the well-characterized microbiome. However, the other communities referred to as 'dark matter' of microbiomes such as viruses (virome), fungi (mycobiome), archaea (archaeome), and helminths have not been completely elucidated. Development of new and improved metagenomics methods has allowed the identification of complete genomes from the genetic material in the human gut, opening new perspectives on the understanding of the gut microbiome composition, their importance, and potential clinical applications. Here, we review the recent evidence on the viruses, fungi, archaea, and helminths found in the mammalian gut, detailing their interactions with the resident bacterial microbiota and the host, to explore the potential impact of the microbiome on host's health. The role of fecal virome transplantations, pre-, pro-, and syn-biotic interventions in modulating the microbiome and their related concerns are also discussed.

Keywords: archaeome; fecal virome transplants; gut microbiota; helminths; mycobiome; virome.

Figure 1

Scientific publications on various microbial communities of the gut microbiome. The number of peer-reviewed scientific publications for (A) microbiome, (B) virome (C) mycobiome and (D) archaeome studies. The list of peer-reviewed literature was collated in a non-systematic manner from the web of science (WOS) all database collection (MEDLINE, Inspec, Biological abstracts, scIELO, KCI, WOS core collection, Russian science index) from 2009 to 2019. The research of literature was performed using keywords like "microbiome”, “gut microbiome”, “gut virome”, “virome”, “gut fungi”, and “gut mycobiome”. * For careful selection of gut archaeome studies, we used PubMed only with keywords like “gut archaea”, “gut archaeon” and “gut archaeome/archaeon” and “archaeome” which includes whole microbiome analysis studies but not limited to only archaeome. Document types excluded were review of the literature (including systematic and meta-analysis), case studies, reports, and abstracts in conferences, workshops, and book chapters.

Figure 2

The microbial cross-kingdom interactions between members of microbiome. All the microbes in the gut interact with each other; Microbes interact with each other (A), with helminths (B) and their hosts, establishing trophic relationship (either symbiotic or parasitic). These interactions are categorized as competition or cooperation for survival, nutrients (C) and adhesion sites (D) on the mucosa. Most of these microbes produce specific metabolites (Short chain fatty acids) (E) and supply energy to intestinal epithelial cells (IEC), influencing the immune system (F–G), and overall homeostasis. DC = Dendritic cells; Mo = Macrophages.

Figure 3

The known microbe–immune interactions in inflammation and homeostasis. A. Certain members of bacteria (intracellular, systemic commensals, Proteobacteria, and opportunist pathogens) and viruses induce inflammatory responses (IR 1) by promoting T cells and their subsets T helper 1 cells (Th 1) releasing pro-inflammatory cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), etc., initiated by microbe-associated molecular patterns (Black arrow). B–C. Segmented filamentous bacteria (extracellular), member of Fungi, and helminths (GATA 3) induce inflammatory responses initiated at the mucosal sites, which promote the expansion of T cells expressing Th 17 and Th 2 cells releasing Interleukins (IL) 17A, IL-22, and IFN-γ, respectively (Brown and green). D. Certain members of Archaea (Methanomassiliicoccus luminyensis, Methanosphaera stadtmanae and M. smithii) promote surface markers CD86, CD197 expressed on T cells releasing Monocyte-derived dendritic cells (MODC), type 1 IFN (Orange). All the factors involving A–D may lead to tissue damage and ultimately inflammation. E–F. Certain members of Clostridia, Bacteroides fragilis, archaea, and helminths induce regulatory responses by promoting Foxp3-expressing T regulatory (Tregs) cells, limiting the activation of Th1, Th2, and Th17 cells (Blue). This regulation and tolerance promote homeostasis.