During the latest decades the development of sophisticated molecular methods has provided deep insight into the composition of the human microbiome, and today more than 900 different bacterial species have been identified from the oral cavity. Oral health is shaped by a symbiotic relationship between the resident oral microbiota and the host. However, local bacterial alterations as a consequence of ecological perturbations may result in dysbiosis, which is considered critical in the pathogenesis of the two major oral diseases, periodontitis and dental caries.
The composition of the oral microbiota has also been suggested to influence general health status, and dysbiosis of the oral microbiota has been linked with general medical diseases such as cardiovascular diseases, diabetes and cancer. Therefore, a symbiotic relationship between the oral microbiota and the host may potentially have positive effects reaching far beyond the borders of the oral cavity.
The purpose of the present review paper is to address latest findings linking the oral microbiota with general health status, and to discuss future perspectives of this area of research.
Introduction
The human body is covered by billions of microorganisms including bacteria, virus, fungi, archaea and protozoa, which are collectively referred to as the human microbiome. Bacterial cells alone outnumber human cells by a 10-fold (). The composition of the resident microbiota is the result of millions of years of symbiotic co-existence between the host and the microbes, which is why today the human body and the microbes that line the inner- and outer body surfaces are collectively referred to, as a unity called the holobiont (). General health (including oral health) is built upon a symbiotic relationship (harmonic co-existence) of the resident oral microbiota and the host immune system. Accordingly, alterations in either of the components, such as loos of bacterial diversity or an over reactive adaptive immune reaction towards the resident microbiota, may create dysbiosis (imbalance), which in turn can lead to general and oral diseases.
The Human Microbiome Project (HMP) founded by National Institutes of Health (NIH) was initiated in 2007, with the aim of characterizing the healthy human microbiome in samples collected from 300 American volunteers (1;3). In 2013, data from 4.788 samples collected from multiple body sites (females: 18 body sites, males: 15 body sites) in 242 participants of the HMP were presented with emphasis on structure, function and diversity of the healthy human microbiome (). Data demonstrated that each body site was harbored by a distinct microbiome, which in terms of composition and functionality reflected the ecological characteristics present at each particular body site. Furthermore, correlation of microbial community compositions and host phenotypic characteristics, such as ethnicity, age and gender were reported, which partly underline the complex symbiotic relationship between the host and the resident microbiome in general health (). The dataset from HMP now serves as a valuable tool containing phylogenetic (16S rRNA) and functional (metagenomic) information on healthy reference microbiomes from various body sites, which can be used for comparison with microbiome data collected from individuals with general medical and oral diseases ().
In the latest decade, a fast growing attention is being paid to the role of the microbiome in sickness and in health. Accordingly, in 2010 a total number of 951 PubMed indexed papers with microbiome in the title were published, whereas in 2018 this number was increased by 10-fold (9050 PubMed index publications). The intestinal (gut) microbiome and the oral microbiome are the two most complex microbiomes found in the human organisms, and those are also the two microbiomes, which have been studied in most detail in health and disease (5;6). When technological progress is made, new techniques have often initially been applied in studies on the gut microbiome, and then subsequently used in studies on the oral microbiome. The gut and the oral cavity are both part of the gastrointestinal tract, and the gut microbiome and the oral microbiome are both critically involved in digestion (7;8). Therefore, dysbiosis in one part of the gastrointestinal microbiome may compromise homeostasis in other parts. Accordingly, this review paper will focus firstly on the role of the gut microbiome and secondly on the role of the oral microbiome in general health status. Finally, future therapeutic possibilities in modulating and transferring microbiomes to establish and maintain oral and systemic health will be discussed. Throughout the text taxonomic terms such as phylum, genus and species will be used in order to describe the findings from different studies on the gut and oral microbiome. Phylum level is a very broad characterization, whereas genus and species level are more precise characterizations of the microorganism described.
The gut microbiome in health and disease
The gut microbiome is the most complex found in the human organism. The predominant part of the gut microbiome is constituted by bacteria (the microbiota) with as much as 1500 different bacterial species identified (). In addition, the gut is also colonized by archaea, yeast and viruses. The four dominant bacterial phyla in the gut are Bacteriodetes, Firmicutes, Actinobacteria and Proteobacteria (). The composition of the gut microbiota varies considerably between individuals, and is largely influenced by diet and lifestyle. The composition of the gut microbiota is also influenced by genetics. Accordingly, a closer resemblance of the gut microbiota has been reported in identical twins compared to siblings, which in turn have closer resemblance than individuals, who are not genetically related (9;10). Furthermore, the composition of the gut microbiota is also influenced by lifestyle, with differences in nutrition and dietary preferences as the main contributors (8;11-13). In fact, it has been suggested that the gut microbiota may be divided into four characteristic ecosystems (enterotypes Three of those enterotypes associate with health, which is presumably compatible with an omnivore type diet, a fibre rich vegetarian diet and a high protein high fat diet, respectively. The fourth enterotype seems to associate with dysbiosis of the gut microbiota for example in patients with inflammatory diseases and diarrhea, with high numbers of Escherichia coli (). However, the use of enterotypes in characterizing the gut microbial community composition is still somewhat controversial ().
The composition of the gut microbiota is constantly stressed by endogenous and exogenous perturbations. For example, traveling causes a transient but fully reversible compositional change of the gut microbiota (16;17). Antibiotics also induce substantial changes to the gut microbiota (). However, a recent study in healthy young adults reported the gut microbiome to be resilient to antibiotics, since the composition of the gut microbiota was almost completely recovered six months after antibiotic treatment ().
The gut microbiota is believed to be critically involved in maintenance of homeostasis and general health. For example, reciprocal interactions of the gut microbiota and the immune system are considered instrumental in adaptive immune homeostasis (20;21). Furthermore, dysbiosis of the gut microbiota has been report
