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RADZIEJOWSKA, Zuzanna, BIELAK, Alicja, GRYTA, Jakub, IWAN, Karolina, JANCZEWSKA, Martyna, KALICKA, Maria,
KRYSA, Tomasz, KOLASA, Agata & SZKLARZ, Magdalena. Microbial alterations of oral cavity and their association with
Pancreatic Cancer. Quality in Sport. 2023;9(1):71-77. eISSN 2450-3118. DOI https://dx.doi.org/10.12775/QS.2023.09.01.009
https://apcz.umk.pl/QS/article/view/42027

The journal has had 20 points in Ministry of Education and Science of Poland parametric evaluation. Annex to the announcement of the Minister of Education and Science of December 21, 2021. No. 32582.
Has a Journal's Unique Identifier: 201398. Scientific disciplines assigned: Economics and finance (Field of social sciences); Management and Quality Sciences (Field of social sciences).
Punkty Ministerialne z 2019 - aktualny rok 20 punktów. Załącznik do komunikatu Ministra Edukacji i Nauki z dnia 21 grudnia 2021 r. Lp. 32582. Posiada Unikatowy Identyfikator Czasopisma: 201398.
Przypisane dyscypliny naukowe: Ekonomia i finanse (Dziedzina nauk społecznych); Nauki o zarządzaniu i jakości (Dziedzina nauk społecznych).

© The Authors 2023;

This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland

Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium,
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Received: 20.01.2023. Revised: 17.01.2023. Accepted: 31.01.2023.

Microbial alterations of oral cavity and their association with Pancreatic Cancer

Zuzanna Radziejowska¹
https://orcid.org/0000-0002-5879-8778
zuza.radziejowska@gmail.com
Alicja Bielak¹
https://orcid.org/0000-0001-9022-1250
aalicja.groszek@gmail.com
Jakub Gryta¹
https://orcid.org/0000-0003-2088-6622
kubagryta74@gmail.com
Karolina Iwan¹
https://orcid.org/0000-0001-6570-4293
iwan.karolina95@gmail.com
Martyna Janczewska²
https://orcid.org/0000-0003-1310-4776
m.janczewska2002@gmail.com
Maria Kalicka¹
https://orcid.org/0000-0002-7246-6737
maria.kalicka96@gmail.com
Tomasz Krysa³
https://orcid.org/0000-0002-9644-1235
tomek.krysa96@gmail.com
Agata Kolasa¹
https://orcid.org/0000-0002-5538-9733
agatakolasa127@gmail.com
Magdalena Szklarz¹
https://orcid.org/0000-0002-6795-8868
magdalena.szklarz1@gmail.com

¹1 Military Clinical Hospital in Lublin, al. Racławickie 23, 20-049 Lublin
²Independent Public Clinical Hospital No. 4 in Lublin St. Jaczewskiego 8, 20-954 Lublin
³Specialist Hospital of Stefan Cardinal Wyszyński in Lublin

Correspondence: Zuzanna Radziejowska, zuza.radziejowska@gmail.com

https://dx.doi.org/10.12775/QS.2023.09.01.009
https://apcz.umk.pl/QS/article/view/42027
http://creativecommons.org/licenses/by-nc-sa/4.0/)


72

Abstract

Introduction: Pancreatic Cancer (PC), while relatively infrequent, remains one of the deadliest cancers as a
result of late diagnosis and absence of preventive measures. Over 50 % of patients diagnosed with PC already
suffer metastasis. Combined with lack of effective treatment, the need arises for universal biomarkers specific to
PC. In the last decades the importance of human microbiota in its upholding of the body homeostasis has been
under radar, in special regards to its association to cancer. Several species of oral microbiome have been linked
to increased or decreased risk of developing pancreatic cancer, most notably P.gingivalis and Fusobacteria.

Purpose of the study: The aim of this study is to collect and summarize existing evidence on connection of oral
microbiome and pancreatic cancer, as well as to assess their potential use in diagnostics of PC .

Material and method: Literature review was performed, in English databases, using keywords : cancer,
pancreatic cancer, pancreatic cancer prevention, oral microbiome, microbe variation, microbial biomarkers.

Results and conclusions: In our systematic review, evident differences between microbial architecture of PC
patients and healthy individuals were observed. The data on association between microbiota and risk of
developing cancer is limited, however it still provides evidence for relationship between microbial composition
and incidence of pancreatic cancer.

Keywords : cancer, pancreatic cancer, pancreatic cancer prevention, oral microbiome, microbe variation,
microbial biomarkers.

Introduction and purpose
Pancreatic Cancer (PC) is 7th most common cause of cancer death worldwide for both sexes, whilst ranked as
the 14th most common cancer in the world, as of 2020 [1] . This discrepancy between incidence and mortality
highlights poor survival rates. Furthermore increased incidence of PC over the past few years, paints a grim
picture for patients worldwide. PC is prone to show little to none specific symptoms in early stages of
development, up until it grows beyond control and spreads around the body. The term ‘pancreatic cancer’ is an
umbrella term which pertains to several pancreatic tumors, although it is most commonly used to describe
pancreatic ductal adenocarcinoma (PDAC). PDAC represents 85 % of all cancers located in the pancreas[2] .The
main obstacle in the treatment of PC is late diagnosis, with more than a half of the patients being diagnosed
while already suffering metastasis, whereby cancer cells are more invasive. At present, 5-year survival rate for
patients with PC is below 10%[3], although on average patients die within 5-8 months of a diagnosis. The only
chance for curative treatment is surgical removal of the tumor, for which only a small percentage of patients
qualify ( 10%- 20 % ). It is also not rid of long period of recovery, post-operative morbidity and cure rate of
25 % [2]. Following this curative scheme does little to improve survival of patients, given that 80 % of
individuals after resection eventually die of disease. Other forms of therapy, such as radiotherapy or
chemotherapy can be beneficial after resection of the tumor, however pancreatic cancer has shown resistance to
both[4]. Combined with lack of specific early symptoms, retroperitoneal location of the pancreas protects
developing cancer from detection.
At this time the efforts taken on increasing efficacy of treatment of PC are focused on prevention, screening and
early detection [4]. In addition to non-modifiable risk factors (age, sex, family history, genetic susceptibility,
blood group,) associated with PC, there is a number of modifiable factors such as smoking, alcohol consumption,
type 2 diabetes and oral health, of which natural microflora of the oral cavity especially fell under the scrutiny of
researchers[4].
Human microbiota consists of various forms of microorganisms, colonizing vast surfaces of the human body
such as skin, oral cavity, respiratory tract, gastrointestinal tract and urogenital tract[3]. Composition of
microbiome is varied depending on age, diet and dietary habits. Oral cavity (OC) is a habitat for over 700 species
of bacteria, which are collectively referred to as oral microbiome. Microbiome population varies depending on
inhabited surface of oral cavity, and includes both pathogenic and mutualistic bacteria[5]. Various habitats of OC
include periodontal pockets, surface of teeth, buccal mucosa and tongue, which displays the highest diversity of
microorganisms[6]. Any change in environmental conditions of OC facilitates the growth of pathogenic bacteria
and increases their potential to create oral diseases. Dysbiosis of OC has been associated with local and systemic
diseases including periodontal disease, dental caries and oral cancer, diabetes, rheumatoid arthritis and
pulmonary disease[5]. Recent data shows a link between alterations in oral microbiome and development of
cancer, most notably of cancers located in the gastrointestinal tract and oral cavity [5]. There is also compelling
evidence from various studies on the correlation between oral bacteria and etiology of colorectal and pancreatic
cancer[5, 6, 7, 8]. Out of numerous diagnostic markers of cancer, none is sufficiently specific to facilitate early
diagnosis of PC. Lack of effective means of diagnosis paired with expeditious development of this disease is



73

reflected in morbidity of this cancer. Thus, the aim of this study is to gather recent findings and provide
comprehensive summary of current state of knowledge about association of human microbiota and oral health to
pancreatic cancer.

Methods:
We carried out literature search using English based databases (PubMed, Springer, The Lancet) looking for
articles referring to pancreatic cancer, oral health and microbiota, favoring more recent works. Keywords used :
“microbiome”, “ oral bacteria”, “oral microbiota”, “mouth diseases”, “pancreatic cancer”, “cancer”. Recent
Studies (from 2010 to 2022) matching this criteria were reviewed, and those most relevant were picked for our
summary.

Results:
Human microbiome is presumed to trigger various immune responses associated with cancer growth, as it was
observed in numerous studies, most notably with Helicobacter pylori playing a role in pathology of gastric
cancer[9]. Similar connection has been observed between carriage of populations of Porphyromonas gingivalis,
Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum in the oral cavity and incidence and
development of PC [5,7,10]. P.gingivalis and A. actinomycetemcomitans are pathogens primarily involved in
triggering of periodontal disease and tooth loss, and those two afflictions are directly linked to development of
PC[5].

Study performed by Gnanasekaran et al. 2020 demonstrated that direct exposure of P.gingivalis on PDAC cells,
induced their proliferation [11]. They established that those pathogens thrive in hypoxic condition and infection
of cancer cells with P.gingivalis was related to enhanced growth of PDAC cells in vivo.
Most of existing clinical studies tend to substantiate the association between the state of oral microflora and a
risk of pancreatic cancer. In 2018 study performed by Fan et al. oral wash samples carrying P.gingivalis and
A.actinomycetemcomitans were linked to increased risk of pancreatic cancer[5]. It was also evaluated that
increased carriage of Fusobacteria and its genus Leptotrichia is connected to decreased risk of PC. It is worth
mentioning that the study was adjusted for risk factors for pancreatic cancer such as age, race, sex, BMI, history
of diabetes, smoking and alcohol consumption.

Correspondingly, risk of developing PC was also observed by Michaud et al. to increase two-fold in population
with high levels of antibodies against P.gingivalis [10] in comparison to individuals with low levels of those
antibodies . Furthermore, they observed 45 % lower risk of developing PC in patients with consistently high
levels of antibodies to commensal oral bacteria in the serum.

It is worth mentioning that 2020 comparative study conducted by Wei et al. provided evidence for correlation
between high abundance of Streptococcus and Leptotrichina and the incidence of PDAC, while simultaneously
Veillonella, Fusobacteria and Neisseria populations increased in healthy control group[13]. This is
contradictionary to findings of Fan et al. which found Leptotrichia to be elevated in control group.
Furthermore, Vogtmann et al. Found Enterobacteriaceae, Lachnospiraceae G7, Bacterioidaceae and
Staphylococcaceae to be associated with increased risk of PC in Iranian population [14]. Those results differ
from the ones obtained on Western and Chinese populations, which may point to existing variability in microbial
population depending on specific place of residence of microbial host.

Torres et al. in the study of 108 patients ( 8 with diagnosed PC, 78 diagnosed with other diseases including
cancer, and 22 healthy control group) observed high levels of Leptotrichia in pancreatic cancer group [15]
similarly to Weit et al, and on the other hand lower levels of Porphyromonas and Neisseria in patients with PC.
However, clear distinction between patients with PC and the other participants was observed, in contrary to
similarities between microbial populations of healthy patients and patients suffering from different diseases than
PC [15] . This highlights the possible importance of oral microbiota in regards to detection of pancreatic cancer.
Significant distinction between the architecture of oral microbiome of healthy patients and PC afflicted group
was observed by Ferrel et al. In their study elevated risk of pancreatic cancer was associated to Gemella adiacens,
while Neisseria elongata and Streptococcus mitis were vice versa decreased in PC patients compared to healthy
control [16].



74

Table 1. Association between alterations of oral microbiome with Pancreatic cancer, summary of clinical
trials
Author Participants Control group Results Location, year
Fan et al. I cohort : 170 PC,

170 controls
II cohort: 191 PC,
201 controls

Matched,
Consisted of
healthy
participants

High abundance of
P.gingivalis and
A.actinomycetemcomitans
were associated with
increased risk of PC,
Fusobacteria connected to
decreased risk of
pancreatic cancer

United
States,(2018)

Michaud et al. 405 PC and 416
controls

Matched Patients with high level of
antibodies against
P.gingivalis had double
the risk of pancreatic
cancer, than patients with
low levels of these
antibodies

Europe, (2013)

Wei et al. 41 PC, 69 controls Matched,
Consisted of
healthy patients

High levels of
Streptococcus and
Leptotrichina were
associated with PC,
Control group had
increased population of
Veillonella and Neisseria

China, 2020

Vogtmann et
al.

273 PC, 285 controls Control group
was clear of PC

Enterobacteriaceae,
Lachnospiraceae G7,
Bacterioidaceae and
Staphylococcaceae were
linked to PC

Iran, 2020

Torres et al. 108 PC, 100 controls 78 participants of
the had other
diseases, 22 were
healthy controls

Ratio of Leptotrichia to
Porphyromonas is
increased in PC

United States, 2015

Petrick et al. 122 PC and 354
controls

Participants were
African-
American only,
controls were
clear of diseases

No association between
any microbial taxa and
risk of PC

United States, 2021

Farrel et al. 38 PC, 27 chronic
pancreatitis, 38
healthy

Double control
group, healthy
group was
matched with
PC; some
samples were
selected for
validation phase

N. elongata and S.mitis
are decreased in PC, while
G.adiacens is increased

United States, 2012

Sun et al. 10 PC, 17 benign
pancreatic disease, 10
healthy

Double control
group

High concentrations of
Fusobacteria and low
concentrations of Neissera
associated with elevated
risk for PC

China, 2020



75

Conversely, Petrick et al. noted lack of significant association between carriage of bacterial microbes and PC in
the study on African Americans. Nonetheless elevated PC risk was noted amongst never smokers, participating
in the study[17]. Authors have pointed to differences between characteristics of population of their study and
other studies performed previously by other researchers. While results for African-American populations didn’t
prove any connection between architecture of oral microbiota and risk of PC, these same connections were found
for white population of their own pool of participants, for this instance corresponding with findings of Fan et al.
as well as Michaud et al. [5,10].
Similarly Kabwe et al. summarized latest literature regarding possible use of oral microbiomes as cancer markers,
and found that it might be arduous to single out a specific bacteria universally linked to PC risks[18]. They also
pointed out that comparing studies with different methodology is crucial to distinguish the connection of oral
microbiome and PC, other than results drafted from oral wash samples only. Proposed role of oral bacteria in
cancer development of distant organs consists of pathogens traversing the blood vessels and via circulatory
system travel to distant tissues. It was observed by Abed at el. that component of oral microbiota such as
Fusobacterium nucleatum, may reach the colon and be directly responsible for local cancer growth [19].
Sun et al. found striking differences in oral bacterium architecture of patients with PC in comparison to patients
suffering from benign pancreatic disease as well as healthy group. Participants with PC were observed to have
higher abundances of Bacterioides, Firmicutes and Fusobacteria[20].
In 2017 meta-analysis provided by Michaud et al. conclusion was drawn that there is consistency of positive
association between periodontal disease and pancreatic cancer in various studies[21] . It highlighted at least 50 %
growth in possible risk of PC for patients with periodontitis, which was supported by at least 3 studies with
statistically significant results[21] .
Variety of results of the above mentioned studies is reflected in variety of oral microbiome, that occurs in
different populations. It is known that there are multiple factors impacting the composition of oral microflora,
such as temperature, pH, oxidation-reduction potential, salinity, saliva, as well as the state of oral hygiene of the
host. At the same time, the composition of the oral microflora is documented to present similarly between
populations of different regions of the world [22]. As Stasiewicz et al. points out in their 2021 article, most of
the studies took an approach on singular microorganisms, sparing little attention to factors like mycobiome and
its possible influence on the connection of oral microbiome and pancreatic cancer.
So far, the findings on possible efficacy of microbial organisms as cancer markers are limited and sometimes
conflicting. Future studies should be conducted with larger population sizes and more thorough adjustment for
other external risks. With that in mind, existing evidence points to a link between oral microbiome and the
development of PC . Identification of microbial species connected to pancreatic cancer can result in development
of easily accessible biomarkers, with practical use in screening of larger populations , as well as oriented
preventive approach to PC, with use of antibiotics and probiotics. The use of microbial biomarker in detection of
cancer, has been evaluated by Guo et al, proving valuable as possible marker of colorectal cancer[24] . Thus,
further exploration of these microbial associations may prove crucial in earlier diagnosis, before the cancer
reaches metastatic phase of growth, and in the establishment of new possibilities of treatment.

Conclusions :
1. Pancreatic Cancer is a multifactorial disease, with many risk factors. With its late diagnosis often at
metastatic phase, staggeringly low 5-year survival rate and lack of effective therapies it becomes an urgent
problem for healthcare professionals. Finding new reliable markers of PC would play a huge role in the
management of the disease.
2. There is established connection between poor oral health (as reflected in periodontitis and edentulism [25])
and the risk of pancreatic cancer.
3. P.gingivalis is notoriously proven to be connected to increased risk of PC, adjusted for external risk factors
such as smoking and alcohol consumption [10,11].
4. There is distinguishable difference between the composition of oral microbiota of patients with PC in
comparison to both healthy patients and those suffering from different diseases. The exact mechanisms behind
those differences remain elusive so far, and require further research. Future studies may provide us with more
clues on how to utilize the composition of oral microflora in prevention of pancreatic cancer.

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