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| REVIEW ARTICLE |
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| Year : 2022 | Volume
: 21
| Issue : 1 | Page : 8-12 |
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Microbiome of the head-and-neck region
Santosh Kumar Swain1, Pragnya Paramita Jena2
1 Department of Otorhinolaryngology and Head and Neck Surgery, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
2 Department of Microbiology, IMS and SUM hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
| Date of Submission | 23-Oct-2021 |
| Date of Decision | 30-Oct-2021 |
| Date of Acceptance | 15-Nov-2021 |
| Date of Web Publication | 30-Jun-2022 |
Correspondence Address:
Dr. Santosh Kumar Swain
Department of Otorhinolaryngology and Head and Neck Surgery, IMS and SUM Hospital, Siksha “O” Anusandhan University, K8, Kalinga Nagar, Bhubaneswar - 751 003, Odisha
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/mj.mj_30_21
The microbiome includes microbes that are both helpful and potentially harmful to the human body. The majority of the microbiome are symbiotic and few are pathogenic. The collaboration of microbial colonizers is thought to help in and regulate bodily function. The rapid development of sequencing techniques and analytical methods is increasing the ability to understand the human microbiome. The importance of the human microbiome in the detection and prevention of the disease has been well established in different anatomical parts; however, there is limited literature or research on the microbiome of the head-and-neck region. Proper understanding of the microbiome in the head-and-neck area can help to differentiate the disease-prone patients from normal persons and is helping to guide the treatment regimens and usage of antibiotics. This can help to control resistance and limit the adverse effects of antibiotic overuse. Understanding by clinicians about dysbiosis can help to treat and even protect from common clinical entities such as tonsillitis and rhinosinusitis. Novel genetic sequencing (16S/next-gen sequencing) is helpful for the accurate identification of bacterial taxa in samples collected from the head-and-neck region and a better understanding of the composition of the otolaryngologic microbiome. In this review article, we discuss details of the head-and-neck microbiome distinguished by all relevant subsites. Keywords: Head-and-neck cancer, larynx, microbiome, oral cavity
How to cite this article:
Swain SK, Jena PP. Microbiome of the head-and-neck region. Mustansiriya Med J 2022;21:8-12 |
| Introduction | |  |
The word microbiome refers to a collaborative environment produced by a diverse number of microscopic microorganisms such as bacteria, viruses, and fungi which thrive in different biological niches of the human body.[1] Every human being consists of at least several microbial cells as human cells, with holistic genomes being overwhelmingly bacteria.[1] Insight into the microbiome in the head-and-neck region can help toward a better understanding of infectious and inflammatory conditions such as chronic rhinosinusitis, otitis media, head-and-neck cancer, and chronic tonsillitis. The culture of surface-level swabs may not be sufficient to identify a holistic sample of microbial diversity and its relationship to a disease state of the head-and-neck area of the human body.[2] Culturing of the microorganisms is a biased method as it excludes several fastidious strains of microbes that are unable to grow in provided culture, and it is intended for targeted methods to the basic treatment of active infection.[2] The role of the microbiome in the etiology and predisposition to head-and-neck diseases like cancer is of increasing interest and there are different investigations carried out for relating microbiome and its association with head-and-neck cancer.[3] Like other surfaces in the human body, the head-and-neck regions are also lined with human-associated microorganisms, the microbiome. Imbalances in the microbiome (dysbiosis) have been associated with diseases. In general, the microbiome of this region is vital for the integrity of the mucosa and modulation of the immune system, as human commensal bacteria have properties of immunomodulatory actions and can ensure a rapid and efficient defense against pathogens by priming their host's immune response. Along with immune system modulation, the commensal bacteria of the mucosa prevent the colonization of the pathogen due to uncontrolled setting in open niches.[4] The microbiome of the head-and-neck region is infrequently reported in the medical literature. This review article aims to discuss the details of epidemiology, oral cavity microbiome, tonsillar microbiome, sinonasal microbiome, laryngeal microbiome, and role of the microbiome for head-and-neck cancer.
| Methods of Literature Search | | |
Multiple systematic methods were used to find current research publications on the microbiome in the head-and-neck region. This search strategy recognized the abstracts of published publications, while other papers were discovered manually from the citations. The literature search strategy was conducted by databases such as PubMed, Scopus, Medline, and Google Scholar with the use of keywords such as microbiome, microbiota, bacteria, oral cavity, oropharynx, nasopharynx, larynx, middle ear, carcinogenesis, mucositis, mucosa and head, and neck cancer. A search strategy using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was developed [Figure 1]. The search was limited to research papers published in English. The references of different studies which included were carefully evaluated for details of microbiome f head and neck that would have been missed during an electronic search. This review article will also serve as a catalyst for additional study into microbiome in the head-and-neck region.
| History | | |
The words microbiome and microbiota are often used interchangeably. however, the term microbiome has a wider meaning representing the genes and genomes of the microbiota and the products of the microbiota and host environment, so it includes plasmid DNA, viruses, arachaea, and fungi even though these not usually detected.[5] The term microbiota/microbiome was first coined in 2001, which describes the entire ecological community, including commensals, symbiotic and pathogenic microorganisms that inhabit the human body in health and disease.[6] Although the gut is considered as the predominant location for microbiome research, current research has begun for the understanding of the head-and-neck microbiome.
| Epidemiology | | |
Approximately 550,000 people are affected by head and neck cancer globally, leading to 380,000 deaths annually.[7] The 5-year survival rate of head and neck cancer is approximately 50%–60% and males are affected 2–4 times more than females.[7] Head and neck cancer refers to malignancies found commonly in the oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, and trachea, of which more than 90% are squamous cell carcinomas.[8] The majority of head-and-neck cancer affecting the oral or oropharyngeal sites have not decreased over the past few years.[9] Recent findings suggest that biological, clinical, and epidemiological research shedding light on the impact of the pathogenesis-associated scenario such as microbiome on the head-and-neck carcinogenesis. The important risk factors for head-and-neck cancer are tobacco use, excessive alcohol consumption, and the human papillomavirus (HPV).[10] However, the occurrence of head-and-neck cancer in patients with none of these risk factors suggests the presence of other etiological risk factors.[9] Most of the head-and-neck malignancies are managed with a high dose of radiation therapy, often along with surgery and chemotherapy. Although these treatment options usually improve the survival of the patients, many develop long-term complications such as xerostomia, caries, and osteoradionecrosis.[11] Radiation-induced caries development in head-and-neck cancer patients along with salivary hypofunction is an important contributor when associate with carbohydrate-rich food which provides a microenvironment in dental plaques of the oral cavity that favors the growth of acidogenic and aciduric bacteria.[11] Prolonged increased levels of acid from the bacterial activity result in demineralization of enamel and causes caries.[12]
| Oral Cavity Microbiome | | |
The human oral cavity or mouth hosts a diverse community of bacteria called as the oral microbiome. Approximately 700 bacteria species have been found in the human oral cavity to date. These bacteria are involved in a wide range of functions and the majority play important role in maintaining oral health.[13] The microbiome of the oral cavity is related to the establishment and progression of premalignant lesions and malignancy of the oral cavity.[14] It enhances the metabolism of alcohol by mediating the formation of acetaldehyde, which results in toxic effects and increases the chance of malignancy, particularly oral cancer.[15] Low acetaldehyde concentrations are seen in germ-free rats which might show an epidemiological link between poor oral cavity hygiene, alcohol consumption, and increased chance of oral cavity cancer.[15] As per the composition of the microbiome, the levels of Streptococcus and Rothia are increased and decreased, respectively, when compared to the contralateral healthy area from the same patients.[16] Furthermore, more salivary counts of Capnocytophaga gingivalis, Prevotella melaninogenica, and Streptococcus mitis were found in persons with oral squamous cell carcinoma when compared to the control group.[17] Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola are currently recognized as the common cause of periodontal disease.[17] Periodontitis is a biofilm-induced inflammatory disease that leads to loss of attachment tissues and alveolar bone, also increasing the chance of developing the chronic systemic disease.[17] A dysbiotic microenvironment has been seen in periodontal inflammation, which is triggered primarily but not exclusively, by Porophyromonas gingivalis. P. gingivalis is thought to provide a keystone impact via host modulation to disrupt homeostasis by remodeling the regular microbiome into disease-provoking conditions.[18] Periodontal diseases have been associated with an increased chance of occurrence or advancement of lung, pancreatic a hematopoietic cancers. However, the exact mechanism for this association is not fully understood.[19] There is a high expression of the human telomerase reverse transcription enzyme demonstrated in patients with periodontitis.[20] This might be due to both periodontitis and cancer present an important disease-oriented pathway linked to cellular differentiation and immortality.
| Otological Microbiome | | |
The ear has three separate parts such as external ear, middle ear, and inner ear. Each part of the ear is distinct, so the microbiome of the ear differs based on the anatomical subsites. One study showed microbiome of the external ear consists of Alloiococcus otitis and Corynebacterium otitidis as core micro-organisms of the healthy external auditory canal.[21] These normal commensal organisms can become pathogenic when inadvertently entered into the middle ear.[21],[22] Another study documented the permeability of the tympanic membrane which transmits acute infections of the external auditory canal into the middle ear and results in otitis media.[23] The analysis of the fluid of the middle ear cleft in otitis media with effusion showed multiple micro-organisms such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.[24] However, perforation of tympanic membrane has etiology for polymicrobial middle ear infections by making communication between outer and middle ear which result in middle ear infections.[24],[25] Chronic otitis media with effusion result in hearing impairment among pediatric patients and is often found in the first decade of life in approximately 80% of cases.[24] The middle ear microbiome has an association with a different compositional difference in patients with chronic otitis media or otitis media with effusion and cholesteatoma in the pediatric age group.[26] The microbiota of the middle ear and adenoids are different. A study documented that hypertrophy of the adenoid may lead to a microbial environment inside the middle ear that differs from a healthy one.[23] In children, the eustachian tube is short in length, horizontal orientation, and decreased rigidity which explains recurrent middle ear infections in pediatric age in comparison to the adult age group.[27] This anatomical difference could theoretically make a route for naso- and oro-pharyngeal microbes to reflux into the middle ear in pediatric age, leading to a microbial environment distinct from that of the adult age middle ear.[23] Middle ear infection with an intact tympanic membrane is likely to originate from the nasopharynx via the eustachian tube. Infants with H. influenza and Streptococcus pneumonaie in the nasopharynx are 33 times more prone to develop otitis media than those with M. catarrhalis.[28] Interestingly, when both middle ears are compared in a single patient with bilateral otitis media with effusion, the similarity of the microbiome was statistically significant, however, no similarity was found from adenoids, highlighting that microbiota of the middle ears is not closely related to that of the nasopharynx.[29],[30]
| Nose and Sinus Microbiome | | |
Chronic rhinosinusitis is a common clinical entity and approximately 31 million people are diagnosed with rhinosinusitis every year in the United States.[31] Many literatures of sinonasal microbiomes can help to expose the etiologies for long-term pathogenesis of it. It is thought that rhinosinusitis is usually a product of patient factors such as allergies and environmental factors which include bacteria, viruses, and biofilms.[31] One study revealed Firmicutes, Proteobacteria, and Actinobacteria were seen in the paranasal sinuses of 28 healthy persons through 16S rRNA sequencing, which serves as a core microbiome, though Staphylococcus aureus and epidermis were found to be the most abundant species.[32] One meta-analysis showed Staphylococcus, Corynebacterium, Actinobacteria, and Streptococcus abundantly found in control and rhinosinusitis patients, whereas other studies suggested that Moraxella and Haemophilus are found in lower abundance.[33] The pathogens like S. pneumoniae and H. influenzae can also be found in healthy paranasal sinuses. It is thought that microbial abundance, as opposed to prevalence, is the critical variable for defining healthy versus diseases paranasal sinuses between normal persons and those with chronic rhinosinusitis.[33] The transition from healthy sinonasal tract to the inflamed sinonasal tract of rhinosinusitis is believed to be caused by fragmentation in the micro-ecological system of the nose and paranasal sinuses, resulting in loss of diversity and the relative overabundance of certain bacteria like Corynebacterium and Actinobacteria.[33]
| Tonsillar Microbiome | | |
Tonsillar infections significantly affect the quality of life and often require tonsillectomy.[34] Tonsillar and adenoid hypertrophy are common clinical entities, especially among children, however, the tonsillar microbiome of humans is lacking in the literature. Currently, the scientific understanding suggests that tonsillar infection with Group A beta-hemolytic streptococci or anaerobic bacteria like Fusobacterium necrophorum and associated loss of microbiome diversity may cause tonsillar disease, though other infection sources hypothesize result polymicrobial pathogenic communities.[35] Streptococcus, Prevotella, and Fusobacterium are commonly seen in pathogenic conditions of the palatine tonsils, such as chronic tonsillitis.[36] Surprisingly, one study stated the nonpathogenic bacteria of the adenotonsillar microbiome such as Streptococcus, Prevotella, and Fusobacterium as important commensal bacteria of the tonsils.[36] This study also reveals that Bacteroidetes and Firmicutes are core commensals species found in this study.[36] This study provides the hypothesis that a lack of possibly protective species gives a pathogenic condition of tonsillitis. More studies are required to solidify the exact role of these species of the tonsillar microbiome.
| Laryngeal Microbiome | | |
In respect to the larynx, a study showed specific changes to the laryngeal microbiome which is directly associated with the onset of the carcinoma of the larynx.[29] At present, the majority of patients are taking proton-pump inhibitors in laryngeal pathology for controlling the reflux.[37],[38] Overuse of this single drug may help researchers to focus on investigations to find the cause for laryngeal inflammation and malignancy of the larynx and increase the scope of treatment strategies.[37] Cigarette smoking and alcohol are important risk factors for causing laryngeal cancer.[39] However, the laryngeal reflux is not significantly associated with the diversity of the laryngeal microbiome as per prediction.[37] One study identified fifteen genera of the bacteria which are potential risk factors of laryngeal malignancy, based on wide differences in abundance among patients with laryngeal carcinoma and those without carcinoma.[39] A study showed that the bacterium Streptococcus is more prevalent in control tissues in comparison to cancerous tissues, indicating that Streptococcus is a more protective microbe than Prevotella or Fusobacterium, these two bacteria found to be increased in number in patients with laryngeal cancer. The mechanism which offers protection by Streptococcus us by interacting with other microbes enhances the oxidative stress protection in the larynx.[40] Interestingly, findings showed that lower quantities of Helicobacter pylori were seen in patients with benign vocal fold pathology despite previously being detected as a pathogen for cancer of the larynx.[41] H. pylori act as a driver for tumorigenesis by enhancing the body's inflammatory response and interfering with epithelial tissue regulatory function.[41] The confusing data on the roles of H. pylori and Streptococcus in the larynx shows that it needs research on their dynamic role in the larynx and the development of laryngeal malignancies.
| Influences of the Microbiome on Head and Neck Cancer | | |
There is a wide range of studies that has been exploring the relationship between the human microenvironment, sustained inflammation, and cancer. Head-and-neck cancer is considered a major public health issue that affects more than half a million new patients every year globally.[9] Oral cavity bacteria often influence the risk of cancer those are consuming alcohol as several commensal bacteria can metabolize ethanol to acetaldehyde. Acetaldehyde is a carcinogenic product.[42] The proportion of head-and-neck cancer is attributed to alcohol in 14.7% and tobacco and alcohol combined is 0.9%.[42] One study showed that a 22-fold increased risk of oropharyngeal cancer associated with oral HPV-16 carriage. HPV is a clear microbial factor for causing cancer in oral and oropharyngeal regions particularly those with cancer sites in HPV carriers; however, the oral cavity bacteria are protective to cancer.[43] Periodontal diseases, loss of the tooth, and infrequent brushing of the tooth are associated with a higher chance of head and neck squamous cell carcinoma. The greater abundance of Corynebacterium kingella, Neisseria, Abiotrophia, Actinomyces, Veillonella, and Capnocytophaga have been related to good oral health rather than diseases of the oral cavity.[44]
| Conclusion | | |
Proper understanding of the microbiome in the head-and-neck region can help clinicians to manage the different populations and disease states. The improved treatment regimens in regards to antibiotic choice, limiting resistance, and limited adverse effects of antibiotic overuse can be happened by clinicians and surgeons with a better understanding of the head-and-neck microbiome. Proper knowledge of head and neck microbiomes help clinicians to view disease state holistically, considering the interactions between microbes. The pathogenic bacteria are thought to contribute to, or manifest disease is often found in healthy states, albeit in lesser abundances, showing that the disease is not caused solely by the species' presence, but rather by the change in the overall composition of the microbiome. More research is required for explaining dysbiosis to understand, treat, and even prevention of common head and neck clinical conditions such as tonsillitis, rhinosinusitis, otitis media, oral cancer, and laryngeal cancer.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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