The Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics in Oral Cancer Management

Probiotics and Antimicrobial Proteins (2023) 15:1298–1311 https://doi.org/10.1007/s12602-022-09985-7 The Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics in Oral Cancer Management Aalina Sakiinah Mohd Fuad1,2 · Nurul Aqilah Amran1,3,4 · Nurrul Shaqinah Nasruddin5 · Nor Aszlitah Burhanudin6 · Stuart Dashper7 · Mohd Hafiz Arzmi1,4,8 Accepted: 22 August 2022 / Published online: 1 September 2022 © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022 Abstract Oral carcinogenesis is preceded by oral diseases associated with inflammation such as periodontitis and oral candidiasis, which are contributed by chronic alcoholism, smoking, poor oral hygiene, and microbial infections. Dysbiosis is an imbalance of microbial composition due to oral infection, which has been reported to contribute to oral carcinogenesis. Therefore, in this review, we summarised the role of probiotics, prebiotics, synbiotics, and postbiotics in promoting a balanced oral microbiome, which may prevent oral carcinogenesis due to oral infections. Probiotics have been shown to produce biofilm, which possesses antibacterial activity against oral pathogens. Meanwhile, prebiotics can support growth and increase the benefit of probiotics. In addition, postbiotics possess antibacterial, anticariogenic, and anticancer properties that potentially aid in oral cancer prevention and treatment. The use of probiotics, prebiotics, synbiotics, and postbiotics for oral cancer management is still limited despite their vast potential, thus, discovering their prospects could herald a novel approach to disease prevention and treatment while participating in combating antimicrobial resistance. Keywords Probiotic · Prebiotic · Synbiotic · Postbiotic · Oral cancer management Introduction * Mohd Hafiz Arzmi 1 Cluster of Cancer Research Initiative IIUM (COCRII), International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia 2 Department of Biomedical Science, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia 3 Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia 4 Jardin Pharma Berhad, Sunway Subang Business Park, Selangor 40150 Shah Alam, Malaysia 5 Department of Diagnostic Craniofacial and Bioscience, Faculty of Dentistry, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia 6 Department of Oral Maxillofacial Surgery and Oral Diagnosis, Kulliyyah of Dentistry, International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia 7 Melbourne Dental School, The University of Melbourne, Melbourne, Victoria 3055, Australia 8 Department of Fundamental Dental and Medical Sciences, Kulliyyah of Dentistry, International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia 13 Vol:.(1234567890) Oral cancer is the 16th most common cancer worldwide with men having a higher incidence and mortality rate compared to women. Asia continent makes up the majority of the total incident (65.8%) and mortality (74%) of lips and oral cancer worldwide, followed by Europe and North America. GLOBOCAN 2020 reported a total of 377,713 new cases and 177,757 mortalities of lip and oral cancer [1]. Tobacco smoking, alcohol drinking, areca nut (betel quid) consumption, and microbial infections such as Human Papilloma Virus and Candida albicans are among the contributing factors to oral carcinogenesis [2]. A study by Kleinstein et al. suggested a new concept in the prevention and treatment of oral diseases through manipulation of the oral microbiome by administering proresolving small lipids molecules to target specific immunemicrobial markers [3]. Another study showed that a balanced oral microbiome may overcome oral diseases that are caused by dysbiosis, subsequently reducing the use of antimicrobial agents, which have been a continuous problem in oral cancer patients due to antimicrobial resistance [4]. Dysbiosis occurs when the equilibrium of an oral microbiome is disturbed. This condition changes the distribution and Probiotics and Antimicrobial Proteins (2023) 15:1298–1311 functional component of the oral microbiome, which may trigger the pathogenicity of opportunistic microorganisms such as C. albicans [5]. Sustained dysbiosis may lead to the colonisation of microbial-mediated inflammation such as C. albicans that have been reported to promote oral carcinogenesis [6]. Furthermore, several cancer-causing pathogens such as Helicobacter spp. can produce genotoxins and other cancer-causing metabolites that induce tumorigenesis [7]. In oral cancer, the association between dysbiosis and carcinogenesis remains unclear. Although oral cancer is commonly associated with alcohol and tobacco use, a study found that poor oral hygiene is among the important risk factor for non-smokers and non-drinkers [8]. Thus, oral carcinogenesis is also suggested to be associated with dysbiosis. Chronic inflammation is one of the hallmarks that contribute to the development of cancer [9]. In oral squamous cell carcinoma (OSCC), periodontitis has been indicated as the facilitating trait of oral cancer development as it is a common inflammatory ailment affecting the oral cavity [10]. Chronic periodontal inflammation is an established risk factor for oral cancer, as patients with chronic inflammation were shown to have a higher risk of developing malignancy compared to healthy individuals [11]. Furthermore, La Rosa et al. reported that stimulation of microorganisms during chronic inflammation increases the expression of inflammatory cytokines and mediators. This would then facilitate mutagenesis, angiogenesis, and uncontrolled cell proliferation, leading to oral cancer [12]. Chronic inflammation associated with periodontal inflammation is commonly caused by anaerobic bacteria such as Fusobacterium, Porphyromonas, and Prevotella. These bacteria release inflammatory mediator that interacts with several types of tissues to induce inflammation. The bacteria also stimulate the release of pro-inflammatory cytokines such as IL-1, IL-6, IL-17, IL-23, tumour-necrosis factor-α (TNF-α), and proteinases that can destroy the extracellular matrix. Some bacteria such as Mycoplasma salivarium, Porphyromonas gingivalis, and Pseudomonas aeruginosa are capable to shift cell proliferation through the initiation of NF-κB and inhibition of apoptosis [12, 13]. Hanahan reported in a study that the oral microbiome possesses the capability to modulate tumorigenesis through immunomodulation, secretion of toxin that contributes to DNA damages, and adhesion to the epithelial receptors to stimulate cell proliferation [14]. Furthermore, in the conditions where the intestinal barrier is disrupted due to dysbiosis, the pathogen can produce butyrate, which possesses pleiotropic and paradoxical effects on differentiated cells in the epithelium, a (...truncated)