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ORAL MEDICINE
THE INFLUENCE OF THE ORAL MICROBIOME
Review Article
ON GENERAL HEALTH
Johannes Friedrich Carl Rohr1a*, Aldis Rozenblats1b , Guntars Selga1c , Ingrīda Čēma1d
1Department of Oral Medicine, Faculty of Dentistry, RSU Institute of Stomatology, Rīga Stradiņš University, Rīga, Latvia
a
Dental Student; e- mail: Jo.Rohr@me.com
b
DDS, MSc, Assistant Professor; e-mail: Aldis.Rozenblats@rsu.lv; ORCIDiD: https://orcid.org/0000-0001-9087-9183
c
DDS, MSc, Associate Professor; e-mail: selga@sveiks.lv; ORCIDiD: https://orcid.org/0000-0003-2363-2644
d
DDS, PhD, Professor, Head of the Department; e-mail: Ingrida.Cema@rsu.lv; ORCIDiD: https://orcid.org/0000-0002-0937-6157
ABSTRACT https://doi.org/10.25241/stomaeduj.2021.8(1).art. 7
Background The oral microbiome hosts a large number of microorganisms that play a critical role in oral and
general health. Many factors can cause dysbiosis of the otherwise beneficial interrelationship between host
and microbiome. Understanding and identifying microbial shifts and keystone pathogens that correlate
with general diseases of the body holds many opportunities.
Objective The aim of this literature review is to present scientific evidence about disease-associated
microbial shifts in the oral cavity, the effect on oral and general health and give the reader insights into
alternative, new treatment approaches. This review is also intended to inspire practitioners to consider a
more holistic care approach.
Data sources A search was performed using PubMed, Google Scholar and ScienceDirect. The general key
terms used were: “Oral microbiome AND health”, “Oral microbiome AND general disease”. Disease-specific
searches were performed. Articles found by cross-referencing were included.
Study selection Original studies and meta-analyses were included. Articles published in 2012 or later were
preferentially considered. Reviews were included if deemed valuable and labelled in the text. Articles not
written in English were excluded.
Data extraction The reviewer assessed each article for their relevance and methodology. Results were
evaluated according to their sample size and whether or not the same result was replicated in different
studies.
Data synthesis Individual etiological factors correlate with several, seemingly unrelated diseases. This article
directs the reader towards understanding the more unusual interconnections and utilizing multidisciplinary
treatment approaches, that are aimed at reestablishing an overall balance within the oral microbiome.
KEYWORDS
Oral Microbiome; Systemic Diseases; Oral Health; Probiotics; Dysbiosis.
1. INTRODUCTION crevices to which aerobe and anaerobe microbes
can adhere, forming biofilms. These extracellular
The human body hosts many complex microbial biofilms are found everywhere from the buccal
communities that influence functions like digestion, mucosa to the tooth surfaces, dorsum of the tongue
metabolic regulation, immune response, and there and gingival sulci. In addition to bacteria, diverse
is evidence that a dysfunctional microbiome promo- forms of fungi, viruses, protozoa and archaea are
tes the development of diseases [1]. Our oral micro- found as part of the normal oral microbiome [2].
biome comprises at least 772 prokaryotic species, Various studies have shown that an unbalanced
second in diversity only to that of the gut. The microflora not only correlates with diseases of the
oral cavity exhibits a large number of surfaces and oral cavity, but those of other organ systems, too [3].
OPEN ACCESS This is an Open Access article under the CC BY-NC 4.0 license.
Peer-Reviewed Article
Citation: Rohr JFC, Rozenblats A, Selga G, Čēma I. The influence of the oral microbiome on general health. Stoma Edu J. 2021;8(1):66-76
Received: February 04, 2021; Revised: February 28, 2021; Accepted: March 09, 2021; Published: March 11, 2021
*Corresponding author: Johannes Friedrich Carl Rohr; Department of Oral Medicine, Faculty of Dentistry, RSU Institute of Stomatology,
20 Dzirciema iela, Rīga, Latvia
Tel/Fax: + 37127065382; e-mail: Jo.Rohr@me.com
Copyright: © 2021 the Editorial Council for the Stomatology Edu Journal.
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The most extensive database documenting all
Review Article
cultivable and uncultivable bacteria of the oral cavity
is the expanded Human Oral Microbiome Database
(eHOMD) [5]. It plays a valuable role for researchers
to understand the composition of the microbiome in
detail, and its function in health and disease.
2. METHODOLOGY
A literature review was performed using PubMed,
Google Scholar and ScienceDirect. A detailed search
using the following keywords was performed: “Oral
microbiome” AND “health”, “systemic diseases”,
“caries”, “periodontal disease”, “cardiovascular
disease”, “Bacteria AND nitric oxide”, “Nitric oxide
AND hypertension”, “antibacterial mouthwash”,
“diabetes mellitus”, “oral cancer”, “Oral squamous
cell carcinoma”, “Alzheimer´s disease”, “respiratory
disease”, “pregnancy”, “probiotics”. Further database
searches were done about specific oral bacteria and
their role in certain diseases and health.
Original research articles published in 2012 or
later, high-quality studies and meta-analyses were
preferentially considered, review articles were added
Figure 1. Enterosalivary nitrate-nitrite-nitric oxide pathway Nitrate (NO3-) if deemed valuable for the reader and were labelled
is ingested and enters the stomach where it is systemically absorbed (A). It in the text. Articles found by cross referencing were
is then concentrated in the salivary glands and released into the oral cavity. also included. Articles not written in English were
Oral bacteria convert nitrate to nitrite (NO2-) (B), which is then swallowed
and converted to NO when it comes into contact with the gastric juice (C).
excluded. The studies were assessed for their
The NO in the lumen of the stomach and the nitrite enter the circulation statistical value and methodology. The results were
where the nitrite also gets converted to NO. NO causes vasodilation and evaluated according to their sample size and
the reduction of blood pressure. whether or not the same result was replicated in
different studies. Ultimately, 82 publications were
The “keystone pathogen” hypothesis suggests that chosen for this review.
certain pathogens that are present in low abundance
can alter a benign microbiome into a dysbiotic one. 3. RESULTS
Identifying and understanding keystone species is
important for the development of new treatment 3.1. Composition of the oral microbiome
strategies [4]. This review is intended to display these In the oral cavity we find an array of different micro-
keystone species in their correlation to oral and bes. In addition to the more commonly considered
general diseases. It also presents alternative, new bacteria, different types of fungi, viruses, protozoa,
treatment strategies. and archaea are present in the oral cavity and
Because the oral cavity acts as the port of entry to appear to be in a symbiotic relationship with the
several different organs, non-oral diseases such as host. Understanding the specific taxa present in
diabetes, cardiovascular, gastrointestinal, liver, lung the core microbiome helps to identify a state that is
and brain disease, as well as some types of cancer, close to being considered “healthy”. Some of these
Rheumatoid disease, Alzheimer´s and pregnancy- taxa will be further discussed in the sections of this
related complications are associated with oral review investigating specific diseases. Research has
microbiome dysbiosis [2]. Because of its direct contact been conducted mainly focusing on the bacteria
with the external environment, the oral cavity faces of the oral cavity. Less is known about the non-
physical, chemical, and biological variables that can bacterial microbiome, which we will therefore not
have damaging effects. General health related to discuss further. A microbiome consists of two main
a healthy oral microbiome is therefore strongly parts. Data from the NIH human microbiome project
influenced by factors such as diet and hygiene [2]. (HMP) revealed that there is an identifiable core
Constant advances in metagenomics and next gene- (“core” – commonly shared taxa) of microorganisms
ration sequencing techniques help characterize that can be found among unrelated individuals
the functional role of microorganisms. Especially in all microbiomes of the body [6]. The largest
16S rRNA sequencing has contributed to revealing core microbiome was found in the oral cavity
the complexity of the oral microbial communities. consisting of 7 taxa. Those being, in the order of
Utilizing this information for diagnostic and thera- their prevalence from high to low: Streptococcus,
peutic purposes holds many opportunities [3]. Pasteurellacaceae (family), Veillonella, Fusobacterium,
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Lactobacillales (family), Prevotella, and Gemella [7]. demineralization while promoting remineralization.
Review Article
This core microbiome is common to all individuals, An environment is created in which commensal
and together with a variable microbiome, it forms a bacteria have an ecological advantage and can
whole microbiome. The variable microbiome of the outcompete acid-tolerant species like Strepto-
oral cavity differs strongly from person to person coccus mutans and Lactobacilli [17]. The measu-
depending on the diet, physiological differences, rement of the reaction that causes the arginine
ethnicity and even socioeconomic status [8]. breakdown in dental plaque, the so-called arginine
deiminase system (ADS), could potentially help
3.2. Development of the oral microbiome in determining the caries risk [18]. Similarly,
The process of developing any microbiome of the adding species that are associated with a healthy
body starts with the acquisition of the mother´s microbiome may increase the buffer capacity of the
microbes at birth. Depending on the type of deli- microbiome and decrease the chance of dysbiosis.
very (vaginal vs. Caesarian section), the newborn Two species, in particular, have shown promising
comes into contact with somewhat different sets results. Streptococcus dentisani and Streptococcus A12
of microorganisms, resulting in differential deve- are capable of increasing the pH of the dental plaque
lopment of the oral microbiome. Children that have and can inhibit the growth of caries associated to
been delivered vaginally show a larger variety of Streptococcus mutans. Streptococcus A12 produces a
oral bacteria three months after birth (79 species protease that plays an important role in the inhibition
compared to 54 in C-section delivery) [9]. It is of bacteriocin production by Streptococcus mutans
however unclear if those differences have an effect [19]. Bacteriocins are known to poison competitive
on the development of diseases later in life. One bacteria. Streptococcus dentisani actually produces
major difference found was the presence of Slackia bacteriocins itself, which help limit the growth of
exigua in over 76% of C-section delivered children pathogenic species [20]. Streptococcus salivarius strain
compared to absence of S. exigua in vaginally M18 has also been found to be effective in reducing
delivered children [9]. S. exigua has been associated plaque and inhibiting Streptococcus mutans [21].
with periodontitis, root canal infections and can be Another approach to probiotic caries treatment
found in intestinal abscesses and extra-oral surgical is supplementation with engineered microbes,
wounds [10,11]. Differences in the development of especially altered Streptococcus mutans strains,
the oral microbiome are also being seen in breastfed that displace native Streptococcus mutans and
compared to formula-fed infants. A larger amount show lower pathogenicity [22]. It is safe to say that
of lactobacilli colonize in the oral cavity of breastfed probiotic supplementation can be effective in
children, which has been found to inhibit the growth preventing caries development, although usage
of other potentially pathogenic bacteria and likely should be managed by a professional, and supple-
contributes positively to the general and oral ments need to be taken regularly to function.
health [12]. In addition to the vertical transmission 3.3.2. Periodontal disease
of microbes at birth and variations in breastfed vs. Another disease that is highly associated with
formula-fed children, the process of ageing and the oral microbiome dysbiosis and presence of
exposure of children to different environments has certain microorganisms is periodontal disease.
been found to affect the oral microbiome as well [13]. The main pathogens involved in periodontal
disease have long been known. Aggregatibacter
3.3. Oral microbiome and oral diseases actinomycetemcomitans, Porphyromonas gingivalis,
3.3.1. Caries Tannerella forsythia, and species of Treponema
Many studies show that the presence of certain and Prevotella, but especially a combination of
bacteria is highly associated with caries in adults species, the so-called “red complex” consisting
and children. Gram-positive bacteria of the genera of Porphyromonas gingivalis, Tannerella forsythia
Streptococcus, Actinomyces, Lactobacillus and Propio- and Treponema denticola, are associated with
nibacterium were found to be the main cause for periodontitis [23]. According to more recent microbial
carious lesions. Specifically, the combination of analyses, Porphyromonas spp., Filifactor alocis and
Streptococcus mutans and Scardovia wiggsiae is Tannerella forsythia and the absence of Neisseria and
often detected in severe childhood caries and Prevotella denticola are considered risk factors of
advanced dentinal caries [14,15]. Other than dietary periodontitis, while the presence of Aggregatibacter
adjustments and fluoride application [16], there are actinomycetemcomitans, Cardiobacterium hominis,
a number of suggested possibilities to prevent caries Peptostreptococcaceae sp., P. alactolyticus and
and aid in caries treatment. Food supplements in the absence of Fretibacterium spp., Fusobacterium
form of prebiotics or probiotics have shown promising naviforme/Fusobacterium nucleatum sub spp.
results. The prebiotic arginine has been shown to Vincentii, Granulicatella adiacens/Granulicatella
prevent dental caries. Arginine is broken down to elegans were associated with aggressive
ammonia, ornithine, CO2 and ATP by commensal periodontitis [24,25]. Fusobacterium necrophorum,
bacteria. Ammonia is an alkaline compound that Lactobacillus acidophilus, Staphylococcus aureus
keeps the pH value close to neutral and prevents and Streptococcus pneumoniae are associated with
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periodontal health [26]. Diagnosing periodontal certain environmental conditions, like increased
Review Article
disease is mainly done by clinical examination and or decreased pH [31]. This might be one of several
predicting its course remains a challenge. Often reasons why the periodontal disease can be hard to
times, periodontitis can reoccur without symptoms, eradicate, and regular maintenance care is highly
and regular examination of all tooth sites is nece- important.
ssary. Diagnostic tools that could give an insight 3.3.3. Oral cancer
into the state of disease-progression are not yet fully Well-known risk factors for oral cancer are tobacco,
developed, but current findings reveal promising alcohol, betel-nut, and human papillomavirus (HPV)
parameters. A recent study reveals that a significant infection [32,33,34]. There is, however, increasing
shift in the taxonomic composition occurs between evidence that the oral microbiome harbors bacterial
the diseased and resolved/healthy state of the species that are highly associated with a variety of
periodontal pockets. While the microbiome is very cancer types. Many recent studies investigate the
similar among different tooth sites in the diseased connection to orodigestive cancers, predominantly
state, a highly variable taxonomic composition has cancers such as oral squamous cell carcinoma, the
been found in the resolved state. This discovery most common malignant transformation of the
would suggest that disrupting the synergistic state head and neck. Chronic inflammation, as present
of a diseased periodontium could help to treat and in the periodontal disease, may be considered
prevent periodontal disease, however, this needs to as a risk factor in cancer development. A meta-
be investigated further [27]. Another study investi- analysis comprising 38 studies with a total of 7184
gated the diagnostic potential of analyzing the salivary participants has found that six periodontal bacteria
proteome. Again, differences in healthy and diseased are associated with the occurrence and prognosis
individuals were recognizable. In patients with of orodigestive cancers, namely Porphyromonas
chronic periodontitis, the amount of salivary proteins gingivalis, Tannerella forsythia, Aggregatibacter
was downregulated. These proteins are associated actinomycetemcomitans, Treponema denticola,
with oral homeostasis and protective functions. Fusobacterium nucleatum and Prevotella intermedia.
The suggested mechanism is that many integral Of those six, two, namely P. gingivalis and P.
salivary proteins are suppressed by the increased intermedia, were associated with a higher incidence
bacterial load and high levels of bacterial proteases of cancer. P. gingivalis infection increased the risk of
[28]. Alternative approaches to established treatment cancer by a factor of 2.16 [35]. No obvious relationship
methods are based on changing the bacterial between the four other species and an increase in
composition in the periodontium. Studies investi- cancer risk was found, although other studies have
gating the additional administration of probiotics stated that T. forsythia, A. actinomycetemcomitans
to mechanical treatment are limited, and so far and T. denticola had positive effects on cancer
have failed in showing lasting clinical improvement progression [36,37,38]. P. gingivalis and F. nucleatum
compared to standard therapy. Patients in the infection were additionally associated with poor
group receiving Lactobacillus rhamnosus SP1 pro- overall survival 14 and might therefore be used
biotic supplements in addition to mechanical as a marker to evaluate the overall prognosis. The
debridement showed a greater reduction in culti- authors concluded that improving oral hygiene and
vable microbiota compared to the group that only treating periodontal disease are important factors
received mechanical debridement in one study, in the prevention and treatment of orodigestive
but clinical improvement showed no significant cancers [35]. Another recent study underlines the
lasting differences [29]. This is in line with the out- findings of the meta-analysis and points out that P.
comes of 13 other publications investigating the gingivalis and F. nucleatum are the dominant bacteria
effect of probiotic supplementation on periodontal correlated with oral squamous cell carcinoma
disease, which are discussed in a systematic review (OSCC). P. gingivalis was found in significantly higher
by Jayaram et al. [30]. Large-scale, long-term abundance in OSCC lesions compared to the tissue
studies are necessary to understand to what extent directly surrounding the cancer and healthy tissues.
probiotic treatment should be administered. Another Furthermore, the bacterium was found in several
approach to specify the state of periodontal disease layers of the tumor, from the epithelial layer to the
is to analyze the bacteriophage community. The deeper tissues. In healthy tissues, it was only found
bacteriophage expression was found to be altered in the epithelial layer. The suggested mechanism was
in the periodontal disease. For example, Santiago- that “P. gingivalis-infected cells escaped the immune
Rodriguez et al. found that in subjects with perio- surveillance function of the host and appeared to
dontal disease, specific lytic bacteriophage genes proliferate rapidly, did not differentiate into maturity
are more highly expressed compared to healthy and then resulted in cancer progression” [39]. P.
controls. The authors assumed that the lytic cycle gingivalis has also been found in esophageal cancer
of some bacteriophages might be supported by lesions and was associated with disease progression
the inflammatory state of periodontal disease. [40]. P. gingivalis may therefore be an important
Lytic bacteriophages increase the stress load on marker for the severity and progression of cancers in
bacteria, which can increase bacterial resistance to the oral cavity and esophagus. As mentioned earlier,
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P. gingivalis is also involved in the development and homeostasis and reduce high blood pressure (Fig.
Review Article
progression of periodontal disease and detection 1). NO is an endogenously produced molecule that
of the bacterium may be useful in evaluating the mainly acts on smooth muscle cells and causes them
disease-severity and treatment-success in both perio- to relax, which results in vasodilation and a reduction
dontitis and oral cancer. In the future, rapid chair-side in systemic blood pressure. NO is normally produced
testing for oral bacteria might become more widely in endothelial cells in an oxidation process that
available. One study has been conducted using a not requires the enzyme nitric oxide synthetase (NOS).
commercially available immunochromatographic Cases, where endogenous NO generation from NOS
detection device, which was specifically made for is compromised, can occur. Endothelial dysfun-
the study and provided immediate chair-side results. ction, for example, is associated with a decrease in
It showed that the detection device accurately NO generation [50]. It is recognized that oral
recognized all P. gingivalis-type strains. No difference bacteria play an important role in the physiology of
to expensive laboratory real-time PCR testing was NO generation that is independent of the enzyme
detected [41]. NOS pathway. Several studies show that supplemen-
tation with nitrate (NO3-) and adhering to a diet
3.4. Oral microbiome and systemic diseases rich in nitrate and nitrite (NO2-) is linked to blood
Many studies suggest links between oral bacteria pressure reduction [51,52]. When dietary nitrate is
and diseases of the pulmonary, cardiovascular and ingested, it enters the circulation and gets absorbed
gastrointestinal system, cancer, diabetes, Alzheimer´s and concentrated in the salivary glands. Up to 25%
and even adverse pregnancy outcomes. After of the ingested nitrate is concentrated in the salivary
tooth brushing, flossing, and dental procedures, glands, which is approximately ten times as much as
bacteremia frequently occurs. Bacteria, toxins and the nitrate concentration in plasma [53]. When the
inflammatory products enter the systemic blood- saliva comes into contact with commensal bacteria
stream and translocate to other sites in the body (mainly on the surface of the tongue), it is converted
where they can cause disease, especially in to nitrite [54]. In the stomach, nitrite is converted to
people that are immunocompromised or have a nitrous acids and NO, that enters the circulation. There
predisposing condition [42,43]. is a clear relationship between nitrate-reducing oral
3.4.1. Cardiovascular disease bacteria and the generation of salivary nitrite [54].
3.4.1.1. Atherosclerosis The bacteria that have been identified to contribute
One predisposing factor for most cardiovascular to optimal nitrate reduction are Actinomyces odonto-
diseases is atherosclerosis, a condition caused by lyticus, Actinomyces viscosus, Actinomyces oris,
the accumulation of atheromatous plaques in vessel Granulicatella adiacens, Haemophilus parainfluenzae,
walls, which have been shown to contain bacte- Neisseria flavescens, Neisseria mucosa, Neisseria
ria typically found in periodontal disease. A. sicca, Neisseria subflava, Prevotella melaninogenica,
actinomycetemcomitans, P. gingivalis, T. forsythia Prevotella salivae, Veillonella dispar, Veillonella
and P. intermedia were previously detected in parvula, and Veillonella atypica [55].
human atheromatous plaque, which suggests that A recent study has shown that tongue cleaning and
these oral pathogens translocated there from the the use of chlorhexidine over a time period of seven
oral cavity [44,45]. These bacteria are able to release days has been shown to increase systolic blood
outer membrane vesicles containing the endotoxin pressure. Subjects that cleaned their tongue several
lipopolysaccharide (LPS). LPS´s are immunomodu- times a day showed a higher increase in blood
lators that can cause an inflammatory response pressure than subjects that cleaned their tongue
when binding to receptors on macrophages or irregularly. Disruption of the papillary surface by
dendritic cells. Atherosclerosis is in turn initiated excessive cleaning of the tongue might increase
by inflammation of arterial endothelial cells [46]. penetration and efficacy of chlorhexidine and there-
Having atherosclerosis increases the risk of stroke. fore reduce the amount of nitrate-reducing bacteria
Stroke has also been found to be causally linked to more than in the group that only irregularly cleaned
periodontal disease, and it has been shown that their tongue. And in fact, differences were identified
regular dental care lowers the risk of stroke [47]. in the tongue microbiome composition between
3.4.1.2. Hypertension and the link to nitric oxide the two groups. Recovery from using chlorhexidine
Multiple recent studies have investigated a link showed an increase in nitrate-reducing bacteria
between the composition of the oral microbiome on the tongue and stabilization of the blood
and increased blood pressure. Two of these present a pressure, which underlines the importance of the
possible connection of childhood caries with arterial oral microbiome in blood pressure regulation [56].
hypertension [48,49]. The increased inflammatory Furthermore, adjusting the diet in patients with
state caused by caries and periodontal disease could increased blood pressure in combination with nitrate
be causative for the increase in blood pressure. supplementation might play an important role in
Oppositely, the presence of certain bacteria that are providing exogenous NO and has been found to be
involved in the so called enterosalivary nitrate-nitrite- beneficial for cardiovascular health [57,58]. Dietary
nitric oxide pathway can affect the nitric-oxide (NO) nitrate is mainly obtained from green leafy vegetables,
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such as rocket, spinach, kale and lettuce and from and Atopobium were found to be significantly less
Review Article
beetroot. Nitrate is also commonly found as a food abundant among patients with diabetes and also
additive in processed meats [59]. Additionally, oral less abundant among obese patients [66]. And in
nitrate-reducing bacteria have an effect on the short- patients with periodontitis and diabetes, Prevotella
term regulation of blood pressure. It was discove- copri, Alloprevotella rava and Ralstonia pickettii
red that they play a role in post-exercise hypotension numbers were increased compared to controls,
(PEH) and skeletal muscle oxygenation. In subjects but normalized after effective glycemic control
that used antibacterial mouthwash, PEH was [67], thus reconstructing the health of the oral
decreased, and so was muscle oxygenation. It seems microbiome. Despite well documented correlations
that regular use of antibacterial mouthwash can of abnormalities of the oral microbiome and
change the composition of the oral microbiome diabetes mellitus, the underlying causal relation-
and make subjects more prone to hypertension ships and potential clinical implications remain to be
[60]. Not only chlorhexidine mouthwash but also elucidated.
the commonly used mouthwash “Listerine” 3.4.3. Alzheimer´s disease
(Johnson & Johnson, New Brunswick, NJ, USA), used Several studies suggest that the presence of
daily, is considered an effective antibacterial pathogenic bacteria in the oral cavity (mainly
agent [61]. In summary, excessive tongue cleaning species also found in periodontal disease) and the
and overuse of antibacterial mouthwash may be development of Alzheimer´s disease (AD) are related.
unfavorable, as it can lead to undesirable shifts in the A study with 158 participants showed that those
oral microbiome. These hygiene regimens are usually who later developed AD (n=35) had significantly
considered beneficial when done in moderation. increased antibody titers against F. nucleatum and
As NO is an omnipresent signaling molecule, P. intermedia compared to healthy individuals, with
effects caused by the oral bacteria involved in NO a milder increase noted in participants that went
production may have an even more significant effect on to develop mild cognitive impairment (n = 46).
on human health than currently assumed. Antibody titers were also elevated for T. denticola and
3.4.2. Diabetes mellitus P. gingivalis [68]. Lipopolysaccharides of P. gingivalis
Recently, indiscriminate use of antibacterial mouth- have also been found postmortem in the brain
wash has also been linked to diabetes mellitus. tissue of AD patients, but not in the control group
According to a study including 945 individuals, the [69]. While abnormal growth of P. gingivalis and
diabetes risk is increased by 55% in individuals using other periodontal pathogens appear to increase the
mouthwash twice a day compared to individuals risk to develop AD, a positive correlation between
using mouthwash less frequently and is increased by the level of pathogens and the severity of AD is not
49% compared to individuals not using mouthwash established. Periodontitis was found to increase the
at all [62]. A possible underlying mechanism was risk of AD in other studies as well, and it was also
reviewed by Sansbury et al. The authors discussed detected that the salivary microbiome was changed
that a reduction of oral bacteria that are part of the in AD patients [70,71]. One of the theories trying
enterosalivary nitrate-nitrite-nitric oxide pathway to explain why periodontitis increases the risk to
reduces NO bioavailability which in turn might develop AD suggests that inflammatory mediators
increase the risk of developing insulin resistance produced by oral bacteria are able to migrate into the
and obesity. The authors however concluded that blood stream and cause an increased systemic pro-
additional research is necessary to substantiate this inflammatory state in the brain [70]. Patients with
hypothesis [63]. Preshaw et al. further discussed AD often show a decline in personal oral hygiene, a
the association of mouthwash and diabetes as factor that might further worsen periodontal health
suggested by Joshipura et al. and pointed out that and the systemic inflammation [72]. To break this
due to methodological limitations, recommending vicious circle, AD patients should be supported
against the use of mouthwash on the basis of this with maintaining good oral hygiene and treated for
study needs to be considered individually [62,64]. If periodontitis if present. Analysis of saliva contents
mouthwash use is recommended or not is a question revealed the presence of brain-proteins that are
that dental professionals are regularly faced with and considered markers of AD. Amyloid-beta levels were
having more background information on the topic higher in mild and moderate AD patients and unchan-
might help in evaluating the potential downsides ged in severe AD patients [73]. Reduced lacto-
and benefits of mouthwash in each individual ferrin levels were detected in patients with mild
case. Correlations between diabetes mellitus cognitive impairment and AD. Interestingly, the level
and alterations of the oral microbiome have been of accuracy those samples provided was higher than
established. In patients with diabetes mellitus, a shift that obtained from cerebrospinal fluid biomarkers
in the oral microbiome has been observed. In an [74] C. Tau-proteins were also found in higher levels in
animal study, increased levels of oral interleukin-17, AD patients compared to the healthy control group
a cytokine promoting inflammation, was detected [75]. Sampling these from saliva rather than from CSF
in diabetic mice [65]. Furthermore, the phylum and/or blood samples is less invasive and therefore
Actinobacteria and especially the genera Actinomyces an interesting and promising method to diagnose
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and monitor the disease, however, as of now, it is less involved in disease development and progression.
Review Article
well established. The bottom-line criterion so far is The traditional treatment of periodontitis possibly
that oral hygiene is highly important in AD patients combined with alternative treatments is important in
and needs to be included in AD therapy along with restoring oral health, and in preventing and treating
the periodontal disease treatment. oral and extra-oral diseases. Ongoing research of
3.4.4. Pneumonia probiotic supplementation is revealing more and
Unhealthy oral cavities host bacteria that are involved more beneficial effects and probiotics specifically
in respiratory infections like pneumonia. Periodontal designed to restore a healthy oral microbiome have
disease has been associated with an increased risk of recently been developed. In this article issues like
acquiring nosocomial pneumonia [76]; in fact, one diet, stress and smoking have not been discussed
study concludes that individuals with periodontitis extensively. It is very well known that stress and
were almost three times as likely to present with smoking are etiological factors for oral microbial
nosocomial pneumonia compared to those without dysbiosis. Diet can affect the microbial communities
periodontitis [77]. Several oral pathogens, including of the body in different ways and it would be worth
P. gingivalis and T. denticola have been associated devoting a separate article to these topics.
with pneumonia [78] and it has been shown that
increased oral hygiene reduces the incidence of 5. CONCLUSION
ventilator associated pneumonia [79].
3.4.5. Pregnancy-related conditions Advanced screening of the oral microbiome has
Maternal infections can lead to adverse pregnancy made it possible to tie seemingly unrelated disea-
related outcomes, including preterm birth and ses to the same etiological factors. This holds
decreased birth weight. The levels of P. gingivalis, considerable potential for early diagnosis and
Tannerella forsythia, Prevotella intermedia and disease prediction. Increasing numbers of keystone
Prevotella nigrescens were found to be significantly pathogens and their specific role are being identified.
higher in preterm births compared to those with Their presence in the oral cavity often correlates with
term deliveries. Additionally, a low maternal IgG microbial dysbiosis and the development of caries,
antibody response to the above-mentioned patho- periodontal disease, oral cancer and a number of
gens increases the risk of a preterm birth [80]. A extra-oral diseases as described in detail above.
recent meta-analysis of 20 articles including 10215 Maintaining good oral hygiene appears to be key to
women concluded that the risk of preterm birth is reduce the risk of developing microbial dysbiosis in
doubled in mothers with periodontitis [81]. The the oral cavity, which includes not overly reducing
results of one study indicate that preventive dental oral bacteria. Many new treatment approaches that
treatment has a beneficial effect on prolongation of directly influence the bacterial composition of the
the pregnancy and birth weight [82]. These results oral microbiome have been discovered in recent
clearly justify the need for preventive dental care years. The overall understanding of the oral micro-
and periodontitis treatment in pregnant women. biome and its role in general health is still limited.
Further research is therefore indispensable.
4. DISCUSSION
CONFLICT OF INTEREST
Advances in the understanding of oral microbial The authors declare no conflict of interest.
communities and their dynamics have revealed a
large level of biodiversity among oral bacteria and ACKNOWLEDGMENTS
are continuously enriching the study of microbiome-
associated diseases. Next-generation sequencing We thank Axel Rohr, PD, Dr. med. habil, Clinical Associate Professor
techniques and especially 16S rRNA gene sequen- at University of British Columbia, Vancouver, British Columbia V6T
cing have helped to identify and characterize 1Z1 Canada for technical help and useful discussions.
complex bacterial communities [3]. For both dental
professionals and patients alike, it is of high impor- AUTHOR CONTRIBUTIONS
tance to realize that maintaining a balanced oral
microbiome is part of maintaining health. Under- JR:Data gathering, data analysis, data interpretation, manuscript
standing the consequences of individual habits is drafting. AR:contributing to the concept and conduction of the
in direct connection to that. It has been established manuscript. GS:critical revision of the manuscript. IC: scientific and
that a large number of oral bacteria are directly technical reviewer of the manuscript.
72 Stoma Edu J. 2021;8(1): 66-76 pISSN 2360-2406; eISSN 2502-0285
Oral microbiome and general health
www.stomaeduj.com
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Johannes Friedrich Carl ROHR
Dental Student
Faculty of Dentistry
Rīga Stradiņš University
Rīga, Latvia
CV
Johannes Rohr is a last year student at the Rīga Stradiņš University, Rīga, Latvia where he started his studies in 2016. His academic
interests include biological dentistry and orthodontics and he believes that the relationship between oral and systemic health
within the context of dental clinical treatment needs to be recognized more.
Stoma Edu J. 2021;8(1): 66-76 pISSN 2360-2406; eISSN 2502-0285 75
Rohr JFC, et al.
www.stomaeduj.com
Questions
Review Article
1. The oral microbiome consists of
qa. Random bacteria that are different in every individual;
qb. A core microbiome that is very similar among different individuals, along with a variable microbiome;
qc. Only bacteria and no viruses;
qd. B and C are correct.
2. Increased oral hygiene is highly recommended for:
qa. Alzheimer´s patients;
qb. Patients with severe dental abrasion;
qc. A generally healthy patient;
qd. All of the above are correct.
3. Oral probiotics can…
qa. Kill specific keystone pathogens directly;
qb. Replace the need of brushing your teeth;
qc. Be effective as an adjunctive treatment;
qd. Have severe side effects.
4. Indiscriminate use of antibacterial mouthwash has been linked to:
qa. An increase in blood pressure and a decrease in post-exercise hypotension;
qb. A decrease in blood pressure and an increase in post-exercise hypotension;
qc. Nothing, using mouthwash as much as possible is beneficial for the oral flora;
qd. Periodontal disease.
Sydney Virtual Congress
26-29 September 2021
www.fdiworlddental.org/fdi-world-dental-congress
76 Stoma Edu J. 2021;8(1): 66-76 pISSN 2360-2406; eISSN 2502-0285