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Science Journal of Public Health
2024; Vol. 12, No. 3, pp. 79-82
https://doi.org/10.11648/j.sjph.20241203.13
*Corresponding author:
† Lin-Yi Li and Jie Zhou are co-first authors.
Received: 22 April 2024; Accepted: 9 May 2024; Published: 24 May 2024
Copyright: © The Author(s), 2024. Published by Science Publishing Group. This is an Open Access article, distributed
under the terms of the Creative Commons Attribution 4.0 License (http://creativecommons.org/licenses/by/4.0/), which
permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
Research Article
Exploration of the Effects of Agarwood Extract on the
Inflammtory Microbiota in the Oral-Gut Axis
Lin-Yi Li1, †, Jie Zhou1, †, Cun-Hao Mao1, Diwas Sunchuri2, Zhuo-Da Yang1,
Xu-Dong Tian1, Zi-Nan Zhan1, Zhu-Ling Guo1, 3, *
1School of Dentistry, Hainan Medical University, Haikou, PR China
2School of International Education, Hainan Medical University, Haikou, PR China
3Department of Health Management Center, The First Affiliated Hospital of Hainan Medical University, Haikou, PR
China
Abstract
Agarwood, as a precious medicinal material with distinctive characteristics from Hainan, has been shown in recent studies to
possess significant anti-inflammatory and antibacterial properties. With the rapid growth in public recognition of health
concepts, oral health has garnered increased attention. The main focus of this study is the impact of agarwood extracts on the
oral-gut axis microbiota. The relationship between the oral and gut microbiota is closely intertwined, where oral microbiota
can directly colonize the intestine via saliva and other means, altering the original microbial composition of the gut and leading
to dysbiosis. For instance, Porphyromonas gingivalis significantly increases in patients with gingivitis and periodontitis, as it
can tolerate the acidic environment of the stomach and colonize the intestines through the gastric barrier. Therefore, oral health
can affect intestinal health. Additionally, oral lesions are evident in patients with intestinal inflammation; such patients, like
those with IBD, exhibit a significant accumulation of oral bacteria in the intestines. Although IBD primarily affects the
intestines, its extraintestinal symptoms, often prominently displayed, include oral manifestations. Hence, intestinal health can
also influence oral health. Agarwood extracts inhibit pathogenic oral microbiota, impedes their colonization in the intestine,
and consequently reduces the likelihood of inflammatory bowel disease.. This article, by introducing the microbiota of
periodontitis and the pathogenesis of inflammatory bowel disease, along with extraintestinal symptoms, the preventive and
inhibitory mechanisms of agarwood extract on the associated microbiota are analyzed, providing new insights for the treatment
of such patients. It underscores the importance of maintaining oral hygiene and preventing oral diseases as well.
Keywords
Agarwood, Oral-Gut Axis Microbiota, Inflammation, Periodontitis, Inflammatory Bowel Disease
Science Journal of Public Health http://www.sciencepg.com/journal/sjph
80
1. Introduction
During periodontitis, various factors such as swallowing
mechanism and diet lead to the accumulation of oral bacteria
in the intestinal contents and mucosal tissues of patients with
intestinal diseases [1]. The aggregation of oral microbiota
alters the original microbial population in the intestine, re-
sulting in dysbiosis. According to the literature, compared to
individuals with periodontal health, patients with periodonti-
tis exhibit reduced diversity and changed composition of gut
microbiota, characterized by an increased ratio of Firmicutes
to Bacteroidetes, and enrichment of bacterial phyla such as
Fusobacteria and Proteobacteria [2]. Similar results were
obtained in animal experiments, where after oral gavage with
Porphyromonas gingivalis for ten cycles in mice, sequencing
of the ileal contents showed that the proportion of Firmicutes
was 55.4% and Bacteroidetes was 38.7% in the P. gingi-
valis-treated mice, while in the control group, Firmicutes
accounted for 72.8% and Bacteroidetes accounted for 17.0%,
with statistically significant differences [3]. The major path-
ways and reasons for the appearance of oral microbiota in the
intestine may include:
1.1. Influence of Periodontitis on Gut
Microbiota
1.1.1. Intraintestinal Pathway
Under physiological conditions, oral microbiota rarely en-
ter the intestine due to protection by gastric acid and alkaline
bile. However, the oral microbiota of patients with periodon-
titis differ significantly from those of orally healthy individ-
uals. Certain types of oral pathogens, such as P. gingivalis,
are significantly elevated in patients with gingivitis and per-
iodontitis. This bacterium can tolerate the acidic environment
of the stomach and traverse the gastric barrier. Additionally,
patients taking certain antibiotics (such as vancomycin) ex-
perience expansion of oral bacteria in the body [4].
1.1.2. Hematogenous Pathway
After an increase in intestinal barrier permeability, oral
bacteria can directly transfer from the mouth to the systemic
circulation. Simultaneously, oral pathogenic bacteria in the
blood of patients with periodontitis can also colonize the
intestine through a compromised intestinal barrier. Literature
review has found that ligature-induced periodontitis in rats
leads to the dissemination of oral bacteria to the liver and
spleen, indicating that the dissemination of oral bacteria can
be determined by the oral disease status [5]. Furthermore,
oral bacteria (Porphyromonas gingivalis: P. gingivalis) have
been collected from the blood of patients with periodontal
disease, and it has been demonstrated that strains of oral
Fusobacterium inoculated hematogenously are more suc-
cessful in tumor colonization, indicating the importance of
the circulatory system as a pathway for oral bacteria trans-
mission [6].
Therefore, in certain situations (such as antibiotic-induced
dysbiosis or intestinal inflammation and diet), the intestine
can provide a niche for ingested oral bacteria, leading to op-
portunistic intestinal colonization by oral bacteria. Once oral
microbiota successfully colonize the intestine, they can be-
come pathogenic factors, inducing immune responses. It has
been reported that several resident oral bacteria are potential
factors contributing to intestinal inflammation, such as cer-
tain members of the oral pathogen family Fusobacteriaceae:
Fusobacterium varium and Fusobacterium nucleatum, which
are enriched in the intestines of inflammatory bowel disease
(IBD) patients, with significantly increased abundance dur-
ing disease activity rather than remission. Thirty-four strains
of Fusobacterium found in the intestines of IBD patients may
originate from the oral cavity [6].
1.2. Impact of Gut Dysbiosis on the Oral Cavity
Oral lesions are common in IBD, and literature review re-
veals that both are closely associated with host immune re-
sponses and local dysbiosis-mediated inflammatory reactions
[7]. Studies have also clearly shown that patients with intes-
tinal inflammation, such as IBD, exhibit a significant en-
richment of oral bacteria in the intestine [8, 9]. Although
IBD primarily affects the intestines, the extraintestinal
symptoms of this disease are often prominent, and the oral
cavity is one of the major affected sites, with involvement
rates reaching up to 50% in cases and up to 80% in pediatric
IBD cases. Patients with IBD often present with nonspecific
inflammatory manifestations such as oral ulcers, gingivitis,
and periodontitis, and microbial examinations can reveal
relevant pathogens. Compared to healthy individuals, IBD
patients have an increased prevalence of oral microbiota and
periodontitis.
In summary, the oral and gut microbiota are interrelated
and mutually influential: the inflammatory state of the oral
cavity can cause gut microbiota dysbiosis through swallow-
ing actions; while inflammation in the gut can also corre-
spondingly affect oral environment and conditions.
2. Results and Analysis
Agarwood, a common name for species of the Aquilaria
and Gyrinops genera, is a precious traditional Chinese me-
dicinal material primarily grown in tropical and subtropical
regions. Agarwood contains several active substances that
exhibit antibacterial and anti-inflammatory effects and has
preservative and deodorizing effects in food. Its component
efficacy mainly include stopping emesis by warming the
stomach, calming the whoop by bring the pneuma to kindey,
and stopping the pains by unclogging the pneuma [10].
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81
Therefore, there are also many agarwood-related health
products on the market. Moreover, the essential oil of do-
mestic agarwood has been found to inhibit the activity of
Staphylococcus aureus, and the essential oils of artificial or
natural agarwood exhibit significantly greater inhibitory ac-
tivity against Gram-positive bacterial strains (Staphylococ-
cus aureus and Bacillus subtilis) than Gram-negative bacteri-
al strains (Escherichia coli) [11, 12].
2.1. Terpenoids
1) Monoterpene compounds: Only (-)-bornyl ferulate has
been isolated domestically [13, 14]. Diterpenoid compounds
possess characteristics such as easy absorption and good
biological activity [15]. Triterpenoid compounds can be ex-
tracted with ethanol, with 3-oxo-22-hydroxyhopane being
the most extensively studied [16].
2) Sesquiterpenoid compounds are one of the primary
chemical components of agarwood, which are categorized
into six types in domestically and internationally [17]. Both
chromone compounds and sesquiterpenoid compounds in
agarwood have significant anti-inflammatory effects [18, 19].
In terms of inflammation, inflammatory responses can acti-
vate complex signaling pathways, among which STAT3, as a
key transcription factor, participates in the signaling of mul-
tiple cytokines and is considered a therapeutic target for in-
hibiting the inflammatory process. Additionally, it has been
found that sesquiterpenoid compounds (68.83%) in agar-
wood essential oil (Chinese eaglewood essential oil, CEEO)
can alleviate inflammation by inhibiting the phosphorylation
of STAT3 signaling transduction and suppressing the pro-
duction and release of IL-1β and IL-6 [20].
The main pathways are as follows: The phosphorylation
of tyrosine (Tyr705) on STAT3 and its entry into the nu-
cleus produce transcriptional responses, promoting the
transcription and expression of inflammatory cytokines,
while inhibiting its phosphorylation alleviates inflammation
and increases the survival rate of sepsis. During inflamma-
tion, activated inflammatory cells such as neutrophils, eo-
sinophils, monocytes, and macrophages secrete large
amounts of pro-inflammatory cytokines such as IL-1β, IL-6,
TNFα, and NO. Among these, IL-1β, as one of the im-
portant pro-inflammatory factors involved in inflammation,
is upstream of the inflammatory response and can induce
the production of various inflammatory cytokines and ef-
fector molecules (such as IL-6). IL-6 is one of the most
important mediators of fever and acute-phase response, and
it is the strongest endogenous inflammatory factor that
triggers systemic inflammatory responses, catalyzing and
amplifying the inflammatory response. Research has found
that the STAT3 pathway can be activated by the inflamma-
tory factor IL-1β. Activated STAT3 forms homodimers or
heterodimers, rapidly enters the nucleus, and can induce the
transcription and expression of pro-inflammatory factors
IL-6 and IL-1β. Inhibiting the phosphorylation of STAT3
tyrosine can reduce the production of pro-inflammatory
factors.
2.2. Chromone
Another major chemical component of agarwood is chal-
cones, which are generally divided into four types:
5,6,7,8-dioxo-2-(2-phenylethyl)chalcones (THPECs),
5,6-epoxy-2-(2-phenylethyl)chalcones(EPECs),
5,6,7,8-tetrahydro-2-(2-phenylethyl)chalcones(DEPECs) and
2-(2-phenylethyl)chalcones (FTPECs) [21, 22].
3. Discussion
A research team from Peking University isolated and
identified 17 compounds from the ethanol extract of culti-
vated agarwood produced by artificial tapping of the"No.2
Tropical science" Aquilaria sinensis. Anti-inflammatory
activity testing results showed that the compounds exhibit-
ed anti-inflammatory activity, with the median inhibition
concentration (IC50) value of (27.81±2.34) μmol/L [23]. In
addition, chromones isolated from ethyl acetate extracts
exhibited strong inhibitory activity against Staphylococcus
aureus, as well as good inhibitory activity against methicil-
lin-resistant Staphylococcus aureus [24]; Some extracts
also showed inhibitory activity against Xanthomonas ory-
zae [25].
4. Conclusion
IBD and periodontitis can be linked through microbiota.
At the same time, antimicrobial components in agarwood
leaves have high medicinal and development value, for ex-
ample, inhibiting the growth of bacteria such as Staphylo-
coccus aureus and reducing the production of inflammatory
factors to alleviate inflammatory reactions as well. Therefore,
agarwood extract can influence the microbiota connection
between periodontitis and IBD to some extent, and in the
future, it may be used in the form of sprays or capsules for
preventive measures and adjustments to microbiota dysbiosis
in the oral cavity and gastrointestinal tract.
Funding
This research was funded by the Health Science Research
Project of Hainan Province (22A200041), Innovative Entre-
preneurial Training Program of Hainan Medical University
(X202311810002).
Conflicts of Interest
The authors declare no conflicts of interest.
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82
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