Is There a Link between Oropharyngeal Microbiome and Schizophrenia? A Narrative Review

The study aimed to examine the impact of the oropharyngeal microbiome in the pathophysiology of schizophrenia and to clarify whether there might be a bidirectional link between the oral microbiota and the brain in a context of dysbiosis-related neuroinflammation. We selected nine articles including three systemic reviews with several articles from the same research team. Different themes emerged, which we grouped into 5 distinct parts concerning the oropharyngeal phageome, the oropharyngeal microbiome, the salivary microbiome and periodontal disease potentially associated with schizophrenia, and the impact of drugs on the microbiome and schizophrenia. We pointed out the presence of phageoma in patients suffering from schizophrenia and that periodontal disease reinforces the role of inflammation in the pathophysiology of schizophrenia. Moreover, saliva could be an interesting substrate to characterize the different stages of schizophrenia. However, the few studies we have on the subject are limited in scope, and some of them are the work of a single team. At this stage of knowledge, it is difficult to conclude on the existence of a bidirectional link between the brain and the oral microbiome. Future studies on the subject will clarify these questions that for the moment remain unresolved.

Nrf2 in the Field of Dentistry with Special Attention to NLRP3

The aim of this review article was to summarize the functional implications of the nuclear factor E2-related factor or nuclear factor (erythroid-derived 2)-like 2 (Nrf2), with special attention to the NACHT (nucleotide-binding oligomerization), LRR (leucine-rich repeat), and PYD (pyrin domain) domains-containing protein 3 (NLRP3) inflammasome in the field of dentistry. NLRP3 plays a crucial role in the progression of inflammatory and adaptive immune responses throughout the body. It is already known that this inflammasome is a key regulator of several systemic diseases. The initiation and activation of NLRP3 starts with the oral microbiome and its association with the pathogenesis and progression of several oral diseases, including periodontitis, periapical periodontitis, and oral squamous cell carcinoma (OSCC). The possible role of the inflammasome in oral disease conditions may involve the aberrant regulation of various response mechanisms, not only in the mouth but in the whole body. Understanding the cellular and molecular biology of the NLRP3 inflammasome and its relationship to Nrf2 is necessary for the rationale when suggesting it as a potential therapeutic target for treatment and prevention of oral inflammatory and immunological disorders. In this review, we highlighted the current knowledge about NLRP3, its likely role in the pathogenesis of various inflammatory oral processes, and its crosstalk with Nrf2, which might offer future possibilities for disease prevention and targeted therapy in the field of dentistry and oral health.

Tetramic Acids Mutanocyclin and Reutericyclin A, Produced by Streptococcus mutans Strain B04Sm5 Modulate the Ecology of an in vitro Oral Biofilm

The human oral microbiome consists of diverse microbes actively communicating and interacting through a variety of biochemical mechanisms. Dental caries is a major public health issue caused by fermentable carbohydrate consumption that leads to dysbiosis of the oral microbiome. Streptococcus mutans is a known major contributor to caries pathogenesis, due to its exceptional ability to form biofilms in the presence of sucrose, as well as to its acidophilic lifestyle. S. mutans can also kill competing bacteria, which are typically health associated, through the production of bacteriocins and other small molecules. A subset of S. mutans strains encode the muc biosynthetic gene cluster (BGC), which was recently shown to produce the tetramic acids, mutanocyclin and reutericyclins A, B, and C. Reutericyclin A displayed strong antimicrobial activity and mutanocyclin appeared to be anti-inflammatory; however the effect of these compounds, and the carriage of muc by S. mutans, on the ecology of the oral microbiota is not known, and was examined here using a previously developed in vitro biofilm model derived from human saliva. While reutericyclin significantly inhibited in vitro biofilm formation and acid production at sub-nanomolar concentrations, mutanocyclin did not present any activity until the high micromolar range. 16S rRNA gene sequencing revealed that reutericyclin drastically altered the biofilm community composition, while mutanocyclin showed a more specific effect, reducing the relative abundance of cariogenic Limosilactobacillus fermentum. Mutanocyclin or reutericyclin produced by the S. mutans strains amended to the community did not appear to affect the community in the same way as the purified compounds, although the results were somewhat confounded by the differing growth rates of the S. mutans strains. Regardless of the strain added, the addition of S. mutans to the in vitro community significantly increased the abundance of S. mutans and Veillonella infantium, only. Overall, this study illustrates that reutericyclin A and mutanocyclin do impact the ecology of a complex in vitro oral biofilm; however, further research is needed to determine the extent to which the production of these compounds affects the virulence of S. mutans.

Acquisition of the arginine deiminase system benefits epiparasitic Saccharibacteria and their host bacteria in a mammalian niche environment

Saccharibacteria are a group of widespread and genetically diverse ultrasmall bacteria with highly reduced genomes that belong to the Candidate Phyla Radiation. Comparative genomic analyses suggest convergent evolution of key functions enabling the adaptation of environmental Saccharibacteria to mammalian microbiomes. Currently, our understanding of this environment-to-mammal niche transition within Saccharibacteria and their obligate episymbiotic association with host bacteria is limited. Here, we identified a complete arginine deiminase system (ADS), found in further genome streamlined mammal-associated Saccharibacteria but missing in their environmental counterparts, suggesting acquisition during environment-to-mammal niche transition. Using TM7x, the first cultured Saccharibacteria strain from the human oral microbiome and its host bacterium Actinomyces odontolyticus, we experimentally tested the function and impact of the ADS. We demonstrated that by catabolizing arginine and generating adenosine triphosphate, the ADS allows metabolically restrained TM7x to maintain higher viability and infectivity when disassociated from the host bacterium. Furthermore, the ADS protects TM7x and its host bacterium from acid stress, a condition frequently encountered within the human oral cavity due to bacterial metabolism of dietary carbohydrates. Intriguingly, with a restricted host range, TM7x forms obligate associations with Actinomyces spp. lacking the ADS but not those carrying the ADS, suggesting the acquired ADS may also contribute to partner selection for cooperative episymbiosis within a mammalian microbiome. These data present experimental characterization of a mutualistic interaction between TM7x and their host bacteria, and illustrate the benefits of acquiring a novel pathway in the transition of Saccharibacteria to mammalian microbiomes.

Oral Prevotella Species and Their Connection to Events of Clinical Relevance in Gastrointestinal and Respiratory Tracts

Prevotella is recognized as one of the core anaerobic genera in the oral microbiome. In addition, members of this genus belong to microbial communities of the gastrointestinal and respiratory tracts. Several novel Prevotella species, most of them of oral origin, have been described, but limited knowledge is still available of their clinical relevance. Prevotella melaninogenica is among the anaerobic commensals on oral mucosae from early months of life onward, and other early colonizing Prevotella species in the oral cavity include Prevotella nigrescens and Prevotella pallens. Oral Prevotella species get constant access to the gastrointestinal tract via saliva swallowing and to lower airways via microaspiration. At these extra-oral sites, they play a role as commensals but also as potentially harmful agents on mucosal surfaces. The aim of this narrative review is to give an updated overview on the involvement of oral Prevotella species in gastrointestinal and respiratory health and disease.

Mesenchymal Stromal/Stem Cells-Derived Exosomes as an Antimicrobial Weapon for Orodental Infections

The oral cavity as the second most various microbial community in the body contains a broad spectrum of microorganisms which are known as the oral microbiome. The oral microbiome includes different types of microbes such as bacteria, fungi, viruses, and protozoa. Numerous factors can affect the equilibrium of the oral microbiome community which can eventually lead to orodental infectious diseases. Periodontitis, dental caries, oral leukoplakia, oral squamous cell carcinoma are some multifactorial infectious diseases in the oral cavity. In defending against infection, the immune system has an essential role. Depending on the speed and specificity of the reaction, immunity is divided into two different types which are named the innate and the adaptive responses but also there is much interaction between them. In these responses, different types of immune cells are present and recent evidence demonstrates that these cell types both within the innate and adaptive immune systems are capable of secreting some extracellular vesicles named exosomes which are involved in the response to infection. Exosomes are 30–150 nm lipid bilayer vesicles that consist of variant molecules, including proteins, lipids, and genetic materials and they have been associated with cell-to-cell communications. However, some kinds of exosomes can be effective on the pathogenicity of various microorganisms and promoting infections, and some other ones have antimicrobial and anti-infective functions in microbial diseases. These discrepancies in performance are due to the origin of the exosome. Exosomes can modulate the innate and specific immune responses of host cells by participating in antigen presentation for activation of immune cells and stimulating the release of inflammatory factors and the expression of immune molecules. Also, mesenchymal stromal/stem cells (MSCs)-derived exosomes participate in immunomodulation by different mechanisms. Ease of expansion and immunotherapeutic capabilities of MSCs, develop their applications in hundreds of clinical trials. Recently, it has been shown that cell-free therapies, like exosome therapies, by having more advantages than previous treatment methods are emerging as a promising strategy for the treatment of several diseases, in particular inflammatory conditions. In orodental infectious disease, exosomes can also play an important role by modulating immunoinflammatory responses. Therefore, MSCs-derived exosomes may have potential therapeutic effects to be a choice for controlling and treatment of orodental infectious diseases.

Relationships Between Oral Microecosystem and Respiratory Diseases

Oral microecosystem is a very complicated ecosystem that is located in the mouth and comprises oral microbiome, diverse anatomic structures of oral cavity, saliva and interactions between oral microbiota and between oral microbiota and the host. More and more evidence from studies of epidemiology, microbiology and molecular biology is establishing a significant link between oral microecosystem and respiratory diseases. Microbiota settling down in oral microecosystem is known as the main source of lung microbiome and has been associated with the occurrence and development of respiratory diseases like pneumonia, chronic obstructive pulmonary disease, lung cancer, cystic fibrosis lung disease and asthma. In fact, it is not only indigenous oral microbes promote or directly cause respiratory infection and inflammation when inhaled into the lower respiratory tract, but also internal environment of oral microecosystem serves as a reservoir for opportunistic respiratory pathogens. Moreover, poor oral health and oral diseases caused by oral microecological dysbiosis (especially periodontal disease) are related with risk of multiple respiratory diseases. Here, we review the research status on the respiratory diseases related with oral microecosystem. Potential mechanisms on how respiratory pathogens colonize oral microecosystem and the role of indigenous oral microbes in pathogenesis of respiratory diseases are also summarized and analyzed. Given the importance of oral plaque control and oral health interventions in controlling or preventing respiratory infection and diseases, we also summarize the oral health management measures and attentions, not only for populations susceptible to respiratory infection like the elderly and hospitalized patients, but also for dentist or oral hygienists who undertake oral health care. In conclusion, the relationship between respiratory diseases and oral microecosystem has been established and supported by growing body of literature. However, etiological evidence on the role of oral microecosystem in the development of respiratory diseases is still insufficient. Further detailed studies focusing on specific mechanisms on how oral microecosystem participate in the pathogenesis of respiratory diseases could be helpful to prevent and treat respiratory diseases.

Genital and Oral Microbiome and Behçet’s Disease Activity

BackgroundThe aetiopathogeneses of Behçet’s Disease (BD) remains elusive with multifactorial genetic and epigenetic factors resulting in multisystemic disease. Oral and genital ulceration are common and influences disease outcome. We hypothesised that dysregulation of genital and oral microbial communities contributes to BD disease activity. 153 BD patients’ samples, 70 matched oral and genital (Female: Male, 58:12; mean age, 42±13.9: 39.3±10.3), 12 unmatched samples; 16s rRNA sequencing utilised and V1/V2 and V3/V4 regions analysed. BD outcomes: oral and genital ulcer severity and BD activity scores, Psychological and Social Well-being scales, Headache Impact Test-6 (HIT-6) were included. All the analyses were performed with R software. ResultsThe alpha and beta diversity had anatomical specificity, with significant differences between genital and oral samples; p values<0.05 irrespective of presence or absence of ulcers. Interestingly, in the genital area Bacteroidota were present (G_U: 29% - 10%) and (G_nU: 27% - 14%) compared to less than 1% oral area of V1/V2 and V3/V4. Proteobacteria were uniquely present with (O_U: 9%) and (O_nU: 12%) in oral, and less than 0.01% in genital area for V3/V4 region. Gender anatomical specific communities were noted: females with genital ulcers Gardnerella, Lactobacillus, Atopobium were significantly increased compared to than males, with V3/V4 analysis indicating that Lactobacillus and Gardnerella were significantly increased by 20 times in females than males (p-adj <0.05). In contrast Peptoniphilus and Corynebacterium were significantly increased in males than females. Streptococcus was significantly increased with oral ulceration, while Veillonella was significantly decreased in patients without oral ulceration. Colchicine had a significant effect on the bacterial abundance irrespective of the presence or absence of ulceration. In this cohort, the WSAS (Work and Social Adjustment Scale) values were higher in active disease. ConclusionOur results suggest that dysregulated microbial communities occur in BD. V1/V2 demonstrates that during episodes of ulceration the pathogenic bacteria genus Escherichia-Shigella appear in both oral and genital ulcers. V3/V4 outcomes show that ulceration in both regions is assigned to genus; Lachnospiraceae, Saccharimonidales, Coriobacteriales. Streptococcus is related to the presence of oral ulcers, while Veillonella is presence when patients are ulcers free may be a useful marker of disease regression.