JSUR Journal

Introduction

The oral microbiome is complex with a diverse composition of bacteria, viruses, and fungi. There are 6 broad bacterial phyla that comprise the core oral microbiome, including Firmicutes, Actinobacteria, Proteobacteria, Fusobacteria, Bacteroidetes, and Spirochetes. [2]However, theoral microbiome also has a variable aspect that can be influenced by genotypic and environmental factors such as age, genetics, stress, smoking, and infection. [3,4] If the dynamic balance of the microbiota is disturbed, beneficial microbiota might be impeded by the proliferation of more aggressive pathogenic species with disease-causing capabilities. [5] Although there are still many unknowns regarding oral microbiome composition and its effects on human health, literature has begun to show that oral microbiome, which is easier to obtain than gut microbiome, dysbiosis has the potential to cause oral and systemic disease, such as cardiovascular, neurodegenerative and respiratory diseases. [6] In our research on the effects of stress on oral microbiome composition, the preliminary data indicated that stress can impact the composition of the oral microbiome and cause an increase in microbiota that are associated with various pathogenic potential. [1] The impact of the oral microbiome on both mental and physical health is not a completely novel concept. However, this is a disconnect. While current literature convincingly suggests that gut microbiome dysbiosis may impact postoperative outcomes, oral microbiome dysbiosis in the context of postoperative complications remains to be explored.

Oral Microbiome Dysbiosis and Systemic Health

The oral microbiota have become well known for their role in in-situ or distant tumor progression due to microbial dysbiosis, colonization, and translocation. [7] Porphyromonas gingivali and Fusobacterium nucleatum are two examples of oral microbiota that have beenlinked to carcinogenesis. [7] Fusobacterium nucleatum from the oral cavity is considered a critical factor in colorectal cancer development and Porphyromonas gingivalis has been strongly associated with pancreatic cancer. [7] In a meta-analysis, six studies with a total of 863 pancreatic cancer cases and 906 controls determined a total of 12 to 17 species and clusters of bacteria such as Porphyromonas, Fusobacteria, Bacteroidetes, Streptococcus and Pasteurellaceae, were correlated with pancreatic cancer. [7,8] Further, in a prospective study with 80 patients who were suspected to have a pancreatic tumor prior to biopsy or surgery found

Streptococcus and Leptotrichina was associated with a higher risk of pancreatic cancer. [9]Although microbiota that is found in the oral microbiome has been detected in pancreatic tumors, the cause for this shift in cancer patients remains unknown due to the multitude of genetic and environmental factors that play a role in the oral microbiome composition. [10] Additionally, pancreatic tumors contain their own microbiome. Recent studies have shown that pancreatic tumors contain select bacteria that are significantly increased than those found in the oral or gut microbiome. [11] An increase in intra-tumoral Mycoplasma generates resistance to the common chemotherapy gemcitabine used to treat pancreatic cancer. [12] Whereas a greater abundance of Pseudoxanthomonas, Saccharopolyspora, and Streptomyces predict a greater long-termsurvival.[12] The current proposed mechanisms of systemic inflammation, direct inoculation, transient bacteremia or analogous environments causing oral microbiome dysbiosis and subsequently pancreatic carcinogenesis has not yet been confirmed. [10] The effects of socioeconomics, genetics, race, ethnicity, age and smoking on the oral microbiome can also play a role in systemic health as shown for pancreatic carcinogenesis, posing a challenge to demonstrate a causal link between oral microbiome dysbiosis predisposing patients to pancreatic cancer. [10] Despite promising prospects for utilizing oral microbiome dysbiosis in precision medicine, the review highlighted multiple research gaps, including understanding oral microbiome effects on postoperative outcomes.

Microbiome Dysbiosis and Postoperative Outcomes

The oral cavity and the gut are the two largest microbial environments. [13] Although the oral cavity and gut are connected anatomically with one another, the microbiome profiles are distinct due to the oral-gut barrier (Figure 1). [13] The oral microbiome can translocate to the gut through oral-gut barrier disruption from factors such as decreased bile acid pool, gastric acid and mucosal integrity. [14] The gut microbiota can translocate to the oral cavity with both intra- and inter-personal manners, such as contaminated foods or fluids. [14] The implication of the translocation of microbiota between the oral cavity and the gut in pathogenesis of cancer has been understudied to date; however, gut microbiome dysbiosis and its effects on postoperative outcomes is becoming more clear. A study on the impact of gut microbiome dysbiosis on postoperative complications in visceral surgery determined the occurrence of anastomotic leakage is highly suggested to be related to gut microbiome composition. [15] Additionally, a review on gut microbiota in the setting of gastrointestinal reconstructive surgery concluded gut microbiota dysbiosis can lead to the postoperative complications of pouchitis, malabsorption and diarrhea but also increase the levels of Faecalibacterium prausnitzii that helps to reduce inflammation in the gastrointestinal tract and improve postoperative healing.¹⁶ Some of the pathogenic bacteria that increase significantly after gastrointestinal surgery are Enterobacteriaceae, Enterococcus, Staphylococcus, and Pseudomonas. [16]Postoperative complications after gastrointestinal surgeryhas been shown to alter the gut microbiome due to factors such as the stress of surgery, tissue  ischemia, exposure to oxygen, types of reconstruction and neoadjuvant chemotherapy. [17] Surgical stress has been shown to increases levels of Escherichia and Enterococcus, ischemia-reperfusion injury increases the abundance of Escherichia species in the gut, and in colorectal tumor samples the presence of Fusobacterium nucleatum is associated with a decreased overall survival rate. [16] Recent studies have shown that in obesity, the gut microbiome has decreased microbial richness associated with increased body weight. [18,19] In fact, gut microbiome changes post-bariatric surgery has been proposed as one of the beneficial outcomes of the procedure. [18] The alteration in microbiota composition after bariatric surgery has been shown to not only help with weight loss but in maintaining the weight lost. [20] Bariatric surgery increases microbial richness and Streptococcus species and causes a decrease in levels of bacteria that have a negative correlationwith the satiety hormone leptin such as Bacteroides, Clostridium, and Prevotella. [20] Although the causative role of the gut microbiome on surgical outcomes is known, additional studies to serially track the composition pre and post-operatively is warranted to create personalized bowel preparation and guide postoperative management for patients [21].

Figure 1: Created with BioRender.com. The oral cavity and the gut are the two largest microbial environments. [13] The oral cavity and gut are connected anatomically with one another; however, the microbiome profiles are distinct due to the oral -gut barrier.¹³ Current studies have shown the oral and gut microbiomes can translocate amongst each other leading to dysbiosis that can promote disease deposition [14].

Discussion

The development of next-generation sequencing has allowed the composition of the oral microbiome to be more thoroughly analyzed and compared between healthy and non-healthy indivudals. [22] As the composition of a healthy microbiome is decoded, its potential integration into personalized medicine to prevent and treat disease is promising. The importance of the oral microbiome in predicting the development of oral or systemic diseases has been recognized but research in oral microbiome dysbiosis and postoperative outcomes is lacking.

This could be attributed to limited larger prospective studies with well-defined cohorts to identify associations between microbiome dysbiosis and surgical complications or the lack of pre-and post-operative screening for dysbiosis. However, the evidence for the association between microbiome dysbiosis and surgical outcomes as well as systemic health is strengthening and should continue to be explored. As oral microbiome disease associations continue to be revealed, modifying the microbiome to prevent or treat disease disposition is the next step in incorporating the oral microbiome into precision medicine [23].

References

1. Stoy S, McMillan A, Ericsson AC and Brooks AE (2023) The effect of physical and psychological stress on the oral microbiome. Front. Psychol 14: 1166168.
2. Wade WG (2013) The oral microbiome in health and disease. Pharmacological research 69: 137-143.
3. Deo PN, Deshmukh R (2019) Oral microbiome: Unveiling the fundamentals. J Oral Maxillofac Pathol 23: 122-128.
4. Georges FM, Do NT, Seleem D (2022) Oral dysbiosis and systemic diseases. Front. Dent. Med 3: 995423.
5. Marsh PD (2018) In Sickness and in Health-What Does the Oral Microbiome Mean to Us? An Ecological Perspective. Adv Dent Res 29: 60-65.
6. Giordano-Kelhoffer B, Lorca C, March Llanes J (2022) Oral Microbiota, Its Equilibrium and Implications in the Pathophysiology of Human Diseases: A Systematic Review. Biomedicines 10: 1803.
7. Sun J, Tang Q, Yu S (2020) Role of the oral microbiota in cancer evolution and progression. Cancer Med 9: 6306-6321.
8. Yuan M, Xu Y, Guo Z (2020) Association of oral microbiome and pancreatic cancer: a systematic review and meta-analysis. Therap Adv Gastroenterol 15: 17562848221123980.
9. Wei AL, Li M, Li GQ (2020) Oral microbiome and pancreatic cancer. World J Gastroenterol 26: 7679-7692.
10. Herremans KM, Riner AN, Cameron ME (2022) The oral microbiome, pancreatic cancer and human diversity in the age of precision medicine. Microbiome 2022.
11. Pushalkar S, Hundeyin M, Daley D (2018) The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. published correction appears in Cancer Discov. Cancer Discov 8: 403-416.
12. McAllister F, Khan MAW, Helmink B, Wargo JA (2019) The Tumor Microbiome in Pancreatic Cancer: Bacteria and Beyond. Cancer Cell 36: 577-579.
13. Park SY, Hwang BO, Lim M (2021) Oral-Gut Microbiome Axis in Gastrointestinal Disease and Cancer. Cancers 13: 2124.
14. Park SY, Hwang BO, Lim M (2021) Oral-Gut Microbiome Axis in Gastrointestinal Disease and Cancer. Cancers 13: 2124.
15. Lederer AK, Chikhladze S, Kohnert E, Huber R, Müller A (2021) Current Insights: The Impact of Gut Microbiota on Postoperative Complications in Visceral Surgery-A Narrative Review. Diagnostics 11: 2099.
16. Shi Y, Cui H, Wang F (2022) Role of gut microbiota in postoperative complications and prognosis of gastrointestinal surgery: A narrative review. Medicine (Baltimore) 101: e29826.
17. Agnes A, Puccioni C, D’Ugo D (2021) The gut microbiota and colorectal surgery outcomes: facts or hype? A narrative review. BMC Surg2021.
18. Debédat J, Clément K, Aron-Wisnewsky J (2019) Gut Microbiota Dysbiosis in Human Obesity: Impact of Bariatric Surgery. Curr Obes Rep 8: 229-242.
19. Liu BN, Liu XT, Liang ZH, Wang JH (2021) Gut microbiota in obesity. World J Gastroenterol 27: 3837-3850.
20. Ulker İ, Yildiran H (2019) The effects of bariatric surgery on gut microbiota in patients with obesity: a review of the literature. Biosci Microbiota Food Health 38: 3-9.
21. Zheng Z, Hu Y, Tang J, Xu W, Zhu W et al. (2023) The implication of gut microbiota in recovery from gastrointestinal surgery. Front. Cell. Infect. Microbiol 13: 1110787.
22. Bang E, Oh S, Ju U (2023) Factors influencing oral microbiome analysis: from saliva sampling methods to next-generation sequencing platforms. Sci Rep 2023.
23. Petrosino JF (2018) The microbiome in precision medicine: the way forward. Genome Med 10.