Ecology of the Oral Microbiome: Beyond Bacteria

Abstract

Although great strides have been made in understanding the complex bacterial community inhabiting the human oral cavity, for a variety of (mainly technical) reasons the ecological contributions of oral fungi, viruses, phages, and the candidate phyla radiation (CPR) group of ultrasmall bacteria have remained understudied. Several recent reports have illustrated the diversity and importance of these organisms in the oral cavity, while TM7x and Candida albicans have served as crucial paradigms for CPR species and oral fungi, respectively. A comprehensive understanding of the oral microbiota and its influence on host health and disease will require a holistic view that emphasizes interactions among different residents within the oral community, as well as their interaction with the host.

Keywords: Candidate phyla radiation; Fungi; Meta-omics; Oral microbiome; Phage.

Figure I. Interaction between first cultivated CPR member, TM7x and its bacterial host XH001

(A) Both fluorescence in situ hybridization and scanning electron microscopy revealed XH001 commonly has short-rod cell shape, while TM7x induces long and hyphal morphology in XH001 by inducing the stress-response genes. TM7x also displayed elongated and bud-like protrusions, in addition to cocci morphology [89]. (B) TM7x has small genome size with reduced gene count consistent with the observed lifestyle as an obligate symbiont [89]. (C) Functional classes of the forty most significantly up-regulated genes in the transcriptomic studies in XH001 upon TM7x binding [89].

Figure II. Three examples of inter-kingdom interactions of C. albicans and their effects on the human host

(A.) Biofilms of C. albicans and S. oralis grow to a greater density than that of either species grown alone. In addition, the dual-species biofilm up-regulated the host protease μ-calpain, which degrades cadherin junctions leading to increased tissue invasion by C. albicans and S. oralis [96, 97]. (B.) Biofilms containing both C. albicans and S. mutans grow to a greater density than that of either species grown alone and are associated with development of severe early childhood caries, due to a C. albicans-mediated up-regulation of S. mutans virulence factors including glucan production [98, 103]. (C.) When grown in co-culture with F. nucleatum, C. albicans is greatly inhibited in its ability to form hyphae. Further, the reduction in hyphae appears to circumvent killing and cytokine production by macrophage, indicating that the co-culture may promote evasion of the host immune system [54].

Figure 1: Key Figure. A systemic approach to the investigation of human oral microbiome

A holistic understanding of human microbiome requires a systemic approach to better study the interactions within and between different oral microbial groups (bacteria, CPR, fungi and virus), their impact on microbial physiology, community ecology, and host homeostasis. State-of-the-art, culture-depended methods, coupled with traditional culture-dependent approaches allow researchers to better identify the characteristics of the microbiome, such as the prevalence and biogeography of all species present, as well as the interactions and metabolic pathways critical to the community and the effects of the community on the host. The application of these approaches has revealed a highly complex oral microbial community with sophisticated and dynamic interspecies interactions, which shape and define the community structure as well as functions. Within the oral microbiome, bacterial-bacterial, bacterial-fungal and bacterial-phage interactions and their impact on host have been extensively documented (solid arrows). Meanwhile, the improved cultivation approach, together with crucial genetic information obtained using culture-independent method resulted in the discovery of distinct bacterial-CPR interactions which could potentially prove to be common in host-associated microbiota (dotted arrows). Furthermore, culture-independent metagenomic analysis also suggested putative interspecies interactions, such as the presence of phage specifically targeting CPR members and direct interaction between CPR and the host (dashed arrows).