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Fusobacterium Nucleatum and Alteration of the Oral Microbiome: from Pregnancy to SARS-COV-2 Infection

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Fusobacterium Nucleatum and Alteration of the Oral Microbiome: from Pregnancy to SARS-COV-2 Infection European Review for Medical and Pharmacological Sciences 2021; 25: 4579-4596 Fusobacterium nucleatum and alteration of the oral microbiome: from pregnancy to SARS-COV-2 infection A. DESSÌ1, A. BOSCO2, R. PINTUS1, G. ORRÙ3, V. FANOS1 1Neonatal Intensive Care Unit, University Hospital of Cagliari, Monserrato, Cagliari, Italy 2Medical Lab, Sports Medicine and Physiotherapy Center, Vinovo, Turin, Italy 3Department of Surgical Sciences, Molecular Biology Service (MBS), University of Cagliari, Cagliari, Italy Angelica Dessì and Alice Bosco contributed equally to this work Key Words: Abstract. – OBJECTIVE: The human being has evolved in close symbiosis with its own eco- Fusobacterium Nucleatum, Sars-Cov-2 infection, logical community of commensal, symbiotic and Microbiome, Oral dysbiosis. pathogenic bacteria. After the intestinal micro- biome, that of the oral cavity is the largest and most diversified. Its importance is reflected not only in local and systemic diseases, but also in Introduction pregnancy since it would seem to influence the placental microbiome. The human beings are inseparable from their MATERIALS AND METHODS: This is a liter- own microbial community, with whom they have ature review of articles published in PubMed evolved over millions of years, establishing a about Fusobacterium Nucleatum and both its implications with systemic and oral health, ad- perfect symbiotic relationship, essential for main- verse pregnancy outcomes, flavors perception taining a good state of health. Indeed, together and its interference in the oral-nasal mucosal they form a real super-organism, where this sym- immunity. biosis is maintained thanks to a dynamic balance. RESULTS: It is in maintaining the microbi- This cooperation brings various benefits to the ome’s homeostasis that the Fusobacterium nu- host organism. It confers resistance to coloniza- cleatum, an opportunistic periodontal pathogen tion by pathogens, supporting both the defensive of the oral cavity, plays a crucial role both as a systems and the antioxidant activity. Moreover, it bridge microorganism of the tongue biofilm, and in maintaining the balance between the differ- favors the correct functionality of the cardiovas- ent species in the oral-nasal mucosal immuni- cular and digestive systems, without forgetting ty also by taste receptors interaction. It is also the important contribution to numerous metabol- involved in the flavor perception and its detec- ic processes1. tion in the oral microbiome of children from the This microbial community was called microbi- first days of life suggests a possible physiolog- ome by Nobel laureate Joshua Lederberg with the ical role. However, the dysbiosis can determine intention of defining a real ecological community its pathogenicity with local and systemic conse- of commensal, symbiotics and pathogenic bacte- quences, including the pathogenesis of respira- tory infections. ria that literally share the body space with the hu- CONCLUSIONS: It is interesting to evaluate man being. Futhermore, nowdays, it is also known its possible correlation with Sars-CoV-2 and that the various microorganisms, the microbiota, the consequences on the microflora of the oral which make up the microbiome are not individual cavity, both to promote a possible broad-spec- single-cell organisms present in free form, but trum preventive action, in favor of all subjects they aggregate in an organized structure firmly for whom, by promoting the eubiosis of the oral attached to the surfaces. This structure is the microbiome, a defensive action could be envis- aged by the commensals themselves but, above biofilm, inside which there is both a close cooper- all, for patients with specific comorbidities and ation and a healthy antagonism between different therefore already prone to oral dysbiosis. species. Within the biofilm there is also a fruitful Corresponding Author: Angelica Dessì, MD; e-mail: [email protected] 4579 A. Dessì, A. Bosco, R. Pintus, G. Orrù, V. Fanos communication between the various components ria, Bacteroidetes, Chlamydiae, Chloroflexi, Fir- through quorum-sensing. The presence of the micutes, Fusobacteria, Gracilibacteria (GN02), microbiome is essential for the human organism Proteobacteria, Spirochaetes, SR1, Synergistetes, in the same way as the set of cells that compose and Saccharibacteria (TM7)5. it. In fact, it is now known how numerous factors The colonization by such a large number of can influence this precious ecosystem which must species is also favored by other factors such as therefore be protected and considered as a whole an optimal temperature (about 37°C), adequate with the host organism2. Pregnancy, as well as hydration (saliva and crevicular fluid), a favor- numerous systemic pathologies, is in fact closely able pH (about 6.5-7) and a richness of nutrients related to the health of the oral microbiome as its including proteins present in saliva, glycoproteins alteration can cause adverse effects. Similarly, and the crevicular fluid. The maintenance of ho- respiratory tract infections seem to be associated meostasis despite the presence of a high microbial with oral health. Thus, it is questionable whether, load, is normally guaranteed by the close collab- in the midst of the Covid-19 pandemic, the pre- oration between the host’s immune system and vention of oral dysbiosis can offer any advantag- the set of resident microorganisms. Indeed, there es. These hypotheses emerge from the analysis is the pro and anti-inflammatory activity of the of the literature concerning the Fusobacterium various bacterial species and the presence in the nucleatum, an opportunistic bacterium of the oral saliva and in the crevicular fluid of both nutrients cavity, a pathogen, essential in the creation of the for the microbiota itself and of molecules with biofilm at the level of the buccal cavity, tongue antimicrobial action including type A immuno- and subgingival plaque3. It plays a key role in globulins, lactoferrin and nitrates1. the onset of periodontal pathology and is related Furthermore, both the cells of the epithelial both to various systemic pathologies and to some mucosa of the oral cavity and those of the im- adverse effects in pregnancy. Therefore, it may mune system act directly and indirectly in main- be interesting to evaluate its presence both during taining the balance within the microbiome6. In gestation, a non-pathological clinical condition fact, there is a close collaboration: the mucosal associated with an alteration of the microbiome, cells express a series of antimicrobial peptides, and in children from birth in order to investi- such as ß-defensins, also capable of stimulating gate its possible function. Moreover, the same APCs7, meaning the Antigen Presenting Cells. alteration of the microbiome can be decisive in These cells, in turn, activate the specific immune infectious diseases of the respiratory tract, such response. The mucosal cells also express chemo- as Sars-Cov-2, both at the pathogenetic level and kines, necessary for the recruitment of mono- as a possible complication. A further correlation cytes and neutrophils, and cytokines, which are between the two microorganisms to be analyzed, also essential for the specific immune response8. is associated with the possible repercussions on In the study by Krisanaprakornkit et al9 it has the olfactory system. been shown that the production of these mole- cules by the cells of the gingival epithelial mu- Oral Microbiome Before and cosa occurs both in response to an inflammatory After Pregnancy stimulus and thanks to the continuous stimulation After the intestinal microbiome, that of the operated by the microbiota. Indeed, purely peri- oral cavity is the largest and most diverse in the odontopathogenic microorganisms such as Por- human body. It hosts more than 700 species of phyronomas (P. gingivalis) do not show the afore- microorganisms that find an excellent habitat in- mentioned properties, as the attempt to escape the side the mouth where they can colonize different human immune system is one of the determining surfaces including teeth, gums, the gingival sul- factors of virulence. In fact, elevated numbers of cus, the palate and the lips4. Among these loca- certain oral bacteria, especially P. gingivalis, has tions, the teeth represent a very particular area as, been correlated with higher incidence of major unlike the mucous membranes, they do not fall fatals diseases like pancreatic cancer and liver apart and can therefore represent a perfect district cirrhosis 10. With regard to this, in recent years, for a firm bacterial adhesion. It is precisely this the correlation between oral microbiota and sys- heterogeneity of surfaces within the oral cavity temic diseases has been studied in greater depth. that justifies a well-varied microbiome. In fact, Even if further investigation is needed11, with the very different microbial species can be found, contribution of new analytical techniques like, for belonging to as many as 12 phyla: Actinobacte- example metagenomics and culturomics, is now 4580 Fusobacterium nucleatum and alteration of the oral microbiome possible to identify a large number of bacterial ilus, Neisseria, Rothia and Streptococcus found species that was hardly detectable before12-14. by various studies in non-pregnant women24,25. This complex balance between the immune sys- The above studies indicates the results of similar tem and the microbiome is fundamental for the investigations carried out previously26. Similarly, well-being of
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