Modification of the Oral Microbiota and Carcinogenesis of the Pancreas and
Antonia Sinesi1*, Stefania Pernarella2, Antonio Sarnataro3, Cinzia Casu4 and Savino Cefola5
1RDH Freelancer Canosa di Puglia, Italy
2 RDH Freelancer Latina, Italy
3RDH Florence, Italy
4Private Dental Practice, Cagliari, Italy
5Private Dental Practise, Barletta, Italy
Submission: June 12, 2020; Published: June 29, 2020
*Corresponding author: Antonia Sinesi, RDH Freelancer Canosa di Puglia, Italy
How to cite this article: Antonia S, Stefania P, Antonio S, Cinzia C, Savino C. Modification of the Oral Microbiota and Carcinogenesis of the Pancreas
and Gastrointestinal Tract. Adv Dent & Oral Health. 2020; 12(5): 555849. DOI: 10.19080/ADOH.2020.12.555849
Introduction: The microbiota present in the human oral cavity can be considered one of the most complex ecosystems of our body, since the various anatomical structures present, teeth, gingival sulcus, palate, tongue and tonsils offer a variety of habitats in which different microbial agents can colonize. Some of the microorganisms present in it play a protective role for our health, g offering resistance to some pathogens, helping to maintain the oral homeostasis, while others may become responsible for triggering oral diseases, like tooth decay, periodontal diseases or oral cancer. Lately the interest of the scientific world is focusing on the presence of these bacteria in tumor sites developed in distant districts, such as the gastrointestinal one. The oral microbiota and its change play an important role in the oncological pathology as for example in the carcinoma of the tongue, pharynx-esophagus, digestive tract, colorectal and pancreas.
Materials and Methods: Gastrointestinal tract cancer is one of the most common cancers worldwide. Numerous studies suggest the involvement of periodontal pathogens and cancer. In this work we considered scientific evidences and literature reviews in which the correlation between periodontal bacteria (F. nucleatum, P. ginvilalis, Tannerella forsizia, Streptococcus anginosus.) and gastro-intestinal cancer are examined and studied.
Results: Several ways in which bacteria can induce carcinogenesis have been highlighted: induction of chronic inflammation, inhibition of the immune response, interference with signaling pathways and cell cycles and support for local metabolism of carcinogens. Among the periodontal pathogenic bacteria, F. nucleatum deserves special attention. It is strongly related to gastrointestinal and pancreatic tumors. Scientific studies have shown a clear association between alteration of the oral microbiota and tumors of the gastro-intestinal tract and pancreas.
Conclusion: Bacterial biodiversity is highly associated with tumors of the gastro-intestinal tract and pancreas. Understanding this association, through the use of molecular diagnostics, can help establish a new way of preventing and diagnosing cancer based on bacterial composition. The monitoring of the microbiota could help to prevent the development of these neoplasms. Some species of the oral microbiota or alterations of the oral ecosystem could be accessible and non-invasive biomarkers for the identification of gastrointestinal tumors. The immune and inflammatory system play a crucial role in the development of the disease with a complex interaction between the host defense system and specific bacterial species. Therefore, a comprehensive understanding of the underlying mechanisms for the prevention and treatment of gastrointestinal tumors is required
The oral cavity has more than 700 different bacterial species. These polymicrobial communities are involved in many important functions, such as immunity, protection against pathogens and the metabolism of food compounds, thus allowing homeostasis to be maintained. A close correlation between periodontal disease and systemic diseases  has been widely demonstrated: Cardiovascular disease, Respiratory tract infection, diabetes,
rheumatoid arthritis , and a close correlation between oral microbiota and cancer . Today cancer is the second leading cause of death in the world. The best-known bacterium associated with the development of gastric cancer in humans is Helicobacter pylori, defined as a class I carcinogen . Parodontal bacteria such as Prevotella sp., Tannerella forsythia, Porphyromonas gingivalis Fusobacterium nucleatum and Porphyromonas gingivalis are strongly associated to the development of intestinal and
pancreatic cancer .
The oral cavity and the entire digestive system, even if
represented by different anatomical regions, are highly colonized
by several microbes. However, studies indicate that oral bacteria
are able to spread throughout the digestive tract to reach the
colon, the last stretch of this apparatus. It is interesting to note
that periodontal bacteria P. gingivalis and Aggregatibacter
actinomycetemcomitans have been linked to the development of
digestive tumors such as primary pancreatic adenocarcinoma6.
Instead species such as Fusobacterium nucleatum have large
invasive properties for intestinal mucosa and involvement in
the development of carcinogenesis [6,7]. Brandilyn A. Peters in
2017 in a prospective study nested in two cohorts showed that
Porphyromonas gingivalis is strongly associated with an increased
risk of esophageal squamous cell carcinoma (ESCC) while
Tannerella forsythia is associated with a higher risk of esophageal
adenocarcinoma  (EAC).
Fan X et al.  selected 361 pancreatic adenocarcinoma
incident and 371 controls matched by two prospective
studies for Porphyromonas gingivalis and Aggregatibacter
actinomycetemcomitans, were associated with higher risk of
pancreatic cancer . Recent epidemiological studies have shown
that poor oral health status and specific blood antibodies for oral
pathogens are associated with an increased risk of pancreatic
cancer . Many scientific evidences show that history of
periodontal disease and tooth loss are associated with an increased
risk of pancreatic cancer . Providing further evidence of
an association of pancreatic cancer risk with P. gingivalis, a
large european cohort found that an elevated concentration of
P. gingivalis’ serum antibodies were associated with a double
increase in cancer risk to pancreas . F. nucleatum expresses
Fad A, an adhesion component of the bacterial cell surface that
binds the cadherin E host, leading to the activation of Z-catenin
. F. nucleatum (Fn) binds E-cadherin and promotes CRC cell
In the colon, periodontal bacteria can alter the composition
of the microbiota, causing an initial intestinal dysbiosis, which
triggers aberrant immune and anti-inflammatory responses,
which over time can be the trigger or cause of the development
of a tumorigenesis process charged to these districts .
Swidsinski  reported, using fluorescence in situ hybridization,
that a dense multispecies bacterial biofilm, including oral bacterial
types, was present inside the pancreatic duct of patients with
calcific pancreatitis; however, the reason why the presence of
bacteria of the same clonal origin, found in the pancreas and in the
oral cavity, is unknown . These bacterial types are found in the
atherosclerotic plaques [17,18] distal esophageal tissue , the
brains of Alzheimer’s patients , and in the unit fetal-placental.
From the studies examined it seems that the microbes present in
the mucosal sites can become part of the tumor microenvironment
of the neoplasm of the aerodigestive tract, and intratumoral
microbes can influence the growth of the cancer and its spread
. The surfaces of the digestive tract are subjected to continuous
abuse, infections from lesions, and this can destroy the integrity of
the mucous membranes themselves. Under normal physiological
conditions, barrier lesions represented by mucous membranes
are rapidly repaired and tissue homeostasis is restored. In cases
where this repair does not take place, the imbalance between
the bacterial species contributes to the continuous lesion of the
barrier and the failure to restore homeostasis and it is precisely
in these contexts that the microbiota can influence carcinogenesis
Three different ways by which microbiota contribute to
carcinogenesis have been identified, increasing, or decreasing a
i. Altering the balance between proliferation and death of
ii. Disturb the functionality of the immune system.
iii. Affecting the metabolism within the host .
Deepening this association between periodontal bacteria
and cancer of the gastro-intestinal tract, through the use of
molecular diagnostics can help establish a new concept for the
prediction or diagnosis of cancer based on bacterial composition.
The microbiological research consists in quantitatively and
qualitatively detecting, in the sample taken, the concentration of
specific periodontal pathogenic bacteria, using the PCR technique
in real time (16S rRNA ) and / or the search for specific highly
sensitive antibodies of periodontal pathogenic bacteria. Therefore,
some species of oral microbiota or displacement of the oral
ecosystem can also serve as easily accessible and non-invasive
biomarkers for highlight high risk of gastrointestinal tumors.
The oral cavity therefore plays a fundamental role because it is
involved in correlations with systemic diseases and tumors. Cancer
prevention requires a multidisciplinary approach that includes
various health professionals such as the doctor and nutritionist,
but an evaluation of the oral cavity by the dental hygienist and
dentist could play a key role in the prevention of gastrointestinal
cancer and pancreas..