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Exploration of the Effects of Agarwood Extract on the Inflammtory Microbiota in the Oral-Gut Axis

Received: 22 April 2024     Accepted: 9 May 2024     Published: 24 May 2024
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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.

Published in Science Journal of Public Health (Volume 12, Issue 3)
DOI 10.11648/j.sjph.20241203.13
Page(s) 79-82
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Agarwood, Oral-Gut Axis Microbiota, Inflammation, Periodontitis, Inflammatory Bowel Disease

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 . The aggregation of oral microbiota alters the original microbial population in the intestine, resulting in dysbiosis. According to the literature, compared to individuals with periodontal health, patients with periodontitis 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 . 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. gingivalis-treated mice, while in the control group, Firmicutes accounted for 72.8% and Bacteroidetes accounted for 17.0%, with statistically significant differences . The major pathways 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 enter the intestine due to protection by gastric acid and alkaline bile. However, the oral microbiota of patients with periodontitis differ significantly from those of orally healthy individuals. Certain types of oral pathogens, such as P. gingivalis, are significantly elevated in patients with gingivitis and periodontitis. This bacterium can tolerate the acidic environment of the stomach and traverse the gastric barrier. Additionally, patients taking certain antibiotics (such as vancomycin) experience expansion of oral bacteria in the body .
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 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 successful in tumor colonization, indicating the importance of the circulatory system as a pathway for oral bacteria transmission .
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 opportunistic intestinal colonization by oral bacteria. Once oral microbiota successfully colonize the intestine, they can become pathogenic factors, inducing immune responses. It has been reported that several resident oral bacteria are potential factors contributing to intestinal inflammation, such as certain 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 during disease activity rather than remission. Thirty-four strains of Fusobacterium found in the intestines of IBD patients may originate from the oral cavity .
1.2. Impact of Gut Dysbiosis on the Oral Cavity
Oral lesions are common in IBD, and literature review reveals that both are closely associated with host immune responses and local dysbiosis-mediated inflammatory reactions . Studies have also clearly shown that patients with intestinal inflammation, such as IBD, exhibit a significant enrichment of oral bacteria in the intestine . 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 swallowing actions; while inflammation in the gut can also correspondingly 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 medicinal 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 . Therefore, there are also many agarwood-related health products on the market. Moreover, the essential oil of domestic agarwood has been found to inhibit the activity of Staphylococcus aureus, and the essential oils of artificial or natural agarwood exhibit significantly greater inhibitory activity against Gram-positive bacterial strains (Staphylococcus aureus and Bacillus subtilis) than Gram-negative bacterial strains (Escherichia coli) .
2.1. Terpenoids
1) Monoterpene compounds: Only (-)-bornyl ferulate has been isolated domestically . Diterpenoid compounds possess characteristics such as easy absorption and good biological activity . Triterpenoid compounds can be extracted with ethanol, with 3-oxo-22-hydroxyhopane being the most extensively studied .
2) Sesquiterpenoid compounds are one of the primary chemical components of agarwood, which are categorized into six types in domestically and internationally . Both chromone compounds and sesquiterpenoid compounds in agarwood have significant anti-inflammatory effects . In terms of inflammation, inflammatory responses can activate complex signaling pathways, among which STAT3, as a key transcription factor, participates in the signaling of multiple cytokines and is considered a therapeutic target for inhibiting the inflammatory process. Additionally, it has been found that sesquiterpenoid compounds (68.83%) in agarwood essential oil (Chinese eaglewood essential oil, CEEO) can alleviate inflammation by inhibiting the phosphorylation of STAT3 signaling transduction and suppressing the production and release of IL-1β and IL-6 .
The main pathways are as follows: The phosphorylation of tyrosine (Tyr705) on STAT3 and its entry into the nucleus 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 inflammation, activated inflammatory cells such as neutrophils, eosinophils, 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 important pro-inflammatory factors involved in inflammation, is upstream of the inflammatory response and can induce the production of various inflammatory cytokines and effector 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 inflammatory 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 chalcones, 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) .
3. Discussion
A research team from Peking University isolated and identified 17 compounds from the ethanol extract of cultivated agarwood produced by artificial tapping of the"No.2 Tropical science" Aquilaria sinensis. Anti-inflammatory activity testing results showed that the compounds exhibited anti-inflammatory activity, with the median inhibition concentration (IC50) value of (27.81±2.34) μmol/L . In addition, chromones isolated from ethyl acetate extracts exhibited strong inhibitory activity against Staphylococcus aureus, as well as good inhibitory activity against methicillin-resistant Staphylococcus aureus ; Some extracts also showed inhibitory activity against Xanthomonas oryzae .
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 example, inhibiting the growth of bacteria such as Staphylococcus 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 Entrepreneurial Training Program of Hainan Medical University (X202311810002).
Conflicts of Interest
The authors declare no conflicts of interest.
References
[1] Kitamoto, S., Nagao-Kitamoto, H., Hein, R., Schmidt, T. M., & Kamada, N. (2020). The Bacterial Connection between the Oral Cavity and the Gut Diseases. Journal of Dental Research, 99(9), 1021-1029.
[2] Lourenço, T. G. B., Spencer, S. J., Alm, E. J., et al. (2018). Defining the gut microbiota in individuals with periodontal diseases: An exploratory study. Journal of Oral Microbiology, 10(1), 1487741.
[3] Arimatsu, K., Yamada, H., Miyazawa, H., et al. (2014). Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Scientific Reports, 4, 4828.
[4] Walker, M. Y., Pratap, S., Southerland, J. H., Farmer-Dixon, C. M., Lakshmyya, K., & Gangula, P. R. (2018). Role of oral and gut microbiome in nitric oxide-mediated colon motility. Nitric Oxide, 73, 81-88.
[5] Tsukasaki, M., Komatsu, N., Nagashima, K., Nitta, T., Pluemsakunthai, W., Shukunami, C.,... Takayanagi, H. (2018). Host defense against oral microbiota by bone-damaging T cells. Nature Communications, 9(1), 701.
[6] Kitamoto, S., & Kamada, N. (2022). Periodontal connection with intestinal inflammation: Microbiological and immunological mechanisms. Periodontology 2000, 98, 142–153.
[7] Muhvic-Urek, M., Tomac-Stojmenovic, M., & Mijandrušic-Sincğic, B. (2016). Oral pathology in inflammatory bowel disease. World Journal of Gastroenterology, 22(25), 5655-5667.
[8] Gevers, D., Kugathasan, S., Denson, L., et al. (2014). The treatment-naive microbiome in new-onset Crohn's disease. Cell Host & Microbe, 15(3), 382-392.
[9] Dinakaran, V., Mandape, S. N., Shuba, K., et al. (2018). Identification of specific oral and gut pathogens in full thickness colon of colitis patients: implications for colon motility. Frontiers in Microbiology, 9, 3220.
[10] Ministry of Health of the People's Republic of China, Pharmacopoeia Committee. (1977). Pharmacopoeia of the People's Republic of China (Part 1). Beijing: People's Health Publishing House.
[11] Mei, W. L., Zeng, Y. B., Wu, J., et al. (2008). Chemical constituents and anti-MRSA activity of Chinese eaglewood essential oil. Chinese Pharmaceutical Journal (English Edition), 17(3), 225-229.
[12] Chen, H., Yang, Y., Xue, J., et al. (2011). Chemical constituents and antibacterial activity of chemically stimulated agarwood, wild agarwood, and healthy agarwood essential oils. Molecules, 16(6), 4884-4896.
[13] Hou, W. B., Li, W., Li, Q., et al. (2016). Research progress on saturated vapor pressure of turpentine system components. Chemical Technology & Development, 45(12), 14-18.
[14] Yang, L., Qiao, L. R., Xie, D., et al. (2012). Chemical constituents of indigenous agarwood in China. China Journal of Chinese Materia Medica, 37(13), 1973-1976.
[15] Dong, R. H., Gao, H. Z., Liu, Z. Y., et al. (2010). Research progress on biological activity of diterpenoids from Labiatae plants. China Pharmacy, 21(07), 651-653.
[16] Lin, L. D., & Qi, S. Y. (2000). Triterpenoid components in Chinese agarwood. China Herbal Medicine, (02), 11-12.
[17] Huo, H. X., Zhu, Z. X., Pang, D. R., et al. Anti-neuroinflammatory sesquiterpenes from Chinese eaglewood.
[18] Wang, S. L., Tsai, Y. C., Fu, S. L., Cheng, M. J., Chung, M. I., & Chen, J. J. (2018). 2-(2-Phenylethyl)-4H-chromen-4-one Derivatives from the Resinous Wood of Aquilaria sinensis with Anti-Inflammatory Effects in LPS-Induced Macrophages. Molecules, 23(2), 289.
[19] Zhao, H., Peng, Q., Han, Z., Yang, L., & Wang, Z. (2016). Three New Sesquiterpenoids and One New Sesquiterpenoid Derivative from Chinese Eaglewood. Molecules, 21(3), 281.
[20] Gao, X. L., Zhang, Q., Huo, H. X., et al. (2019). Agarwood essential oil exerts anti-inflammatory effects by inhibiting p-STAT3 and IL-1β/IL-6 production. Chinese Pharmaceutical Journal, 54(23), 1951-1957.
[21] Li, J., Chen, D., Jiang, Y., et al. (2013). Identification and quantification of 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones in Chinese eaglewood by HPLC with diode array detection. Journal of Separation Science, 36(23), 3733-3740.
[22] Yang, J., Dong, W., Kong, F., et al. (2016). Characterization and analysis of 2-(2-phenylethyl)-chromone derivatives from agarwood by artificial holing for different times. Molecules, 21(7), 911.
[23] Zhang, L., Wang, H., Dong, W. H., et al. (2023). Chemical constituents and anti-inflammatory activity of cultivated agarwood. China Herbal Medicine, 54(03), 695-703.
[24] Anonymous. (2015). Study on antibacterial activity components. [Doctoral dissertation, Guangdong Pharmaceutical University].
[25] Peng, D. Q., Wang, C. H., Liu, Y. Y., et al. (2021). Research progress on chemical constituents and pharmacological activities of agarwood. Chinese Journal of Modern Applied Pharmacy, 38(03), 358-365.
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    Li, L., Zhou, J., Mao, C., Sunchuri, D., Yang, Z., et al. (2024). Exploration of the Effects of Agarwood Extract on the Inflammtory Microbiota in the Oral-Gut Axis. Science Journal of Public Health, 12(3), 79-82. https://doi.org/10.11648/j.sjph.20241203.13

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    Li, L.; Zhou, J.; Mao, C.; Sunchuri, D.; Yang, Z., et al. Exploration of the Effects of Agarwood Extract on the Inflammtory Microbiota in the Oral-Gut Axis. Sci. J. Public Health 2024, 12(3), 79-82. doi: 10.11648/j.sjph.20241203.13

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    AMA Style

    Li L, Zhou J, Mao C, Sunchuri D, Yang Z, et al. Exploration of the Effects of Agarwood Extract on the Inflammtory Microbiota in the Oral-Gut Axis. Sci J Public Health. 2024;12(3):79-82. doi: 10.11648/j.sjph.20241203.13

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  • @article{10.11648/j.sjph.20241203.13,
      author = {Lin-Yi Li and Jie Zhou and Cun-Hao Mao and Diwas Sunchuri and Zhuo-Da Yang and Xu-Dong Tian and Zi-Nan Zhan and Zhu-Ling Guo},
      title = {Exploration of the Effects of Agarwood Extract on the Inflammtory Microbiota in the Oral-Gut Axis
    },
      journal = {Science Journal of Public Health},
      volume = {12},
      number = {3},
      pages = {79-82},
      doi = {10.11648/j.sjph.20241203.13},
      url = {https://doi.org/10.11648/j.sjph.20241203.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sjph.20241203.13},
      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.
    },
     year = {2024}
    }
    

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    AB  - 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.
    
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Author Information
  • School of Dentistry, Hainan Medical University, Haikou, PR China

  • School of Dentistry, Hainan Medical University, Haikou, PR China

  • School of Dentistry, Hainan Medical University, Haikou, PR China

  • School of International Education, Hainan Medical University, Haikou, PR China

  • School of Dentistry, Hainan Medical University, Haikou, PR China

  • School of Dentistry, Hainan Medical University, Haikou, PR China

  • School of Dentistry, Hainan Medical University, Haikou, PR China

  • School of Dentistry, Hainan Medical University, Haikou, PR China; Department of Health Management Center, The First Affiliated Hospital of Hainan Medical University, Haikou, PR China

  • Abstract
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    1. 1. Introduction
    2. 2. Results and Analysis
    3. 3. Discussion
    4. 4. Conclusion
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