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1.
Salivary Trefoil Factor Family (TFF) Peptides and Their Roles in Oral and Esophageal Protection: Therapeutic Potential.
Hoffmann, W
International journal of molecular sciences. 2021;(22)
Abstract
Human saliva is a complex body fluid with more than 3000 different identified proteins. Besides rheological and lubricating properties, saliva supports wound healing and acts as an antimicrobial barrier. TFF peptides are secreted from the mucous acini of the major and minor salivary glands and are typical constituents of normal saliva; TFF3 being the predominant peptide compared with TFF1 and TFF2. Only TFF3 is easily detectable by Western blotting. It occurs in two forms, a disulfide-linked homodimer (Mr: 13k) and a high-molecular-mass heterodimer with IgG Fc binding protein (FCGBP). TFF peptides are secretory lectins known for their protective effects in mucous epithelia; the TFF3 dimer probably has wound-healing properties due to its weak motogenic effect. There are multiple indications that FCGBP and TFF3-FCGBP play a key role in the innate immune defense of mucous epithelia. In addition, homodimeric TFF3 interacts in vitro with the salivary agglutinin DMBT1gp340. Here, the protective roles of TFF peptides, FCGBP, and DMBT1gp340 in saliva are discussed. TFF peptides are also used to reduce radiotherapy- or chemotherapy-induced oral mucositis. Thus, TFF peptides, FCGBP, and DMBT1gp340 are promising candidates for better formulations of artificial saliva, particularly improving wound healing and antimicrobial effects even in the esophagus.
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2.
[Protein arginine deiminase of oral microbiome plays a causal role in the polyarthritis rheumatoid initiating].
Desclos-Theveniau, M, Bonnaure-Mallet, M, Meuric, V
Medecine sciences : M/S. 2020;(5):465-471
Abstract
In the last decade, the association between the periodontitis and rheumatoid arthritis (RA) has been established, suggesting that oral microbiome plays a causal role by initiating this chronic autoimmune inflammatory disease of articulation. Both pathogenesis are similar in term of chronic inflammation, tissue breakdown and bone resorption. Molecular aspects have also revealed that citrullination, a post-translational modification catalyzed by peptidyl-arginine deiminases (PADs), is involved in both diseases. For RA, citrullinated proteins production leads to the synthesis the of anti-citrullinated protein antibodies triggering the loss of immune tolerance. In humans, five PADs have been identified. Recently, studies have found that only Porphyromonas species possess PAD. Thus, a major periodontal pathogen, Porphyromonas gingivalis, is able to generate citrullinated epitopes, and could consequently induce anti-citrullinated protein antibodies. In this review, citrullination process, periodontitis and RA are described to put them in relation with molecular, clinical and epidemiological studies establishing the association between periodontitis and RA.
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3.
The Role of Exopolysaccharides in Oral Biofilms.
Cugini, C, Shanmugam, M, Landge, N, Ramasubbu, N
Journal of dental research. 2019;(7):739-745
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Abstract
The oral cavity contains a rich consortium of exopolysaccharide-producing microbes. These extracellular polysaccharides comprise a major component of the oral biofilm. Together with extracellular proteins, DNA, and lipids, they form the biofilm matrix, which contributes to bacterial colonization, biofilm formation and maintenance, and pathogenesis. While a number of oral microbes have been studied in detail with regard to biofilm formation and pathogenesis, the exopolysaccharides have been well characterized for only select organisms, namely Streptococcus mutans and Aggregatibacter actinomycetemcomitans. Studies on the exopolysaccharides of other oral organisms, however, are in their infancy. In this review, we present the current research on exopolysaccharides of oral microbes regarding their biosynthesis, regulation, contributions to biofilm formation and stability of the matrix, and immune evasion. In addition, insight into the role of exopolysaccharides in biofilms is highlighted through the evaluation of emerging techniques such as pH probing of biofilm colonies, solid-state nuclear magnetic resonance for macromolecular interactions within biofilms, and super-resolution microscopy analysis of biofilm development. Finally, exopolysaccharide as a potential nutrient source for species within a biofilm is discussed.
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4.
The probiotics in dentistry: a narrative review.
Pujia, AM, Costacurta, M, Fortunato, L, Merra, G, Cascapera, S, Calvani, M, Gratteri, S
European review for medical and pharmacological sciences. 2017;(6):1405-1412
Abstract
The total number of microbes that colonize the human body is far greater than the number of cells that make it up. In recent years, it has been shown that bacteria play an essential role in the body; in fact, they are essential for the maturation of the intestine, the development and control of the immune system, the development of the brain, the metabolism of macronutrients, the synthesis of vitamins, and the energy balance. Bacteria play an essential role in defense of their territory against the entry of other bacteria that may be pathogenic to health. Metchnikoff, about a century ago, invented probiotics, assuming that the use of certain bacteria could be beneficial to maintaining health. Bacteria colonize our body from birth and breastfeeding, using the bacterial flora of the mother by accessing newborns through the mouth. Antibiotic therapies in pregnancy or cesarean section prevent this flow of probiotics to infants and open the way for very important diseases, such as diabetes and obesity. The alterations of oral bacterial flora are responsible for numerous diseases of the oral cavity and the idea of the use of probiotics is leading the way to new therapeutic perspectives.
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5.
Ecological Therapeutic Opportunities for Oral Diseases.
Hoare, A, Marsh, PD, Diaz, PI
Microbiology spectrum. 2017;(4)
Abstract
The three main oral diseases of humans, that is, caries, periodontal diseases, and oral candidiasis, are associated with microbiome shifts initiated by changes in the oral environment and/or decreased effectiveness of mucosal immune surveillance. In this review, we discuss the role that microbial-based therapies may have in the control of these conditions. Most investigations on the use of microorganisms for management of oral disease have been conducted with probiotic strains with some positive but very discrete clinical outcomes. Other strategies such as whole oral microbiome transplantation or modification of community function by enrichment with health-promoting indigenous oral strains may offer more promise, but research in this field is still in its infancy. Any microbial-based therapeutics for oral conditions, however, are likely to be only one component within a holistic preventive strategy that should also aim at modification of the environmental influences responsible for the initiation and perpetuation of microbiome shifts associated with oral dysbiosis.
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Oral colostrum priming shortens hospitalization without changing the immunomicrobial milieu.
Romano-Keeler, J, Azcarate-Peril, MA, Weitkamp, JH, Slaughter, JC, McDonald, WH, Meng, S, Latuga, MS, Wynn, JL
Journal of perinatology : official journal of the California Perinatal Association. 2017;(1):36-41
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Abstract
OBJECTIVE Oral colostrum priming (OCP) after birth in preterm infants is associated with improved weight gain and modification of the oral immunomicrobial environment. We hypothesized that OCP would modify salivary immune peptides and the oral microbiota in preterm infants. STUDY DESIGN We conducted a prospective, randomized clinical trial to determine the effects of OCP on salivary immune peptide representation in preterm infants (<32 weeks completed gestation at birth). Saliva samples were collected before and after OCP. Salivary immune peptide representation was determined via mass spectroscopy. Oral microbiota representation was determined via sequencing of the 16S rRNA gene. RESULTS Neonates who received OCP (n=48) had a 16-day reduction in the median length of hospitalization as compared with infants who did not receive OCP (n=51). No differences in salivary immune peptide sequence representation before OCP between groups were found. Longitudinal changes in peptides were detected (lysozyme C, immunoglobulin A, lactoferrin) but were limited to a single peptide difference (α-defensin 1) between primed and unprimed infants after OCP. We found no difference in microbial diversity between treatment groups at any time point, but diversity decreased significantly over time in both groups. OCP treatment marginally modified oral taxa with a decline in abundance of Streptococci in the OCP group at 30 days of life. CONCLUSIONS OCP had neither an effect on the salivary peptides we examined nor on overall oral bacterial diversity and composition. Infants who received OCP had a reduced length of hospitalization and warrants further investigation.
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Application of Metagenomic Analyses in Dentistry as a Novel Strategy Enabling Complex Insight into Microbial Diversity of the Oral Cavity.
Burczynska, A, Dziewit, L, Decewicz, P, Struzycka, I, Wroblewska, M
Polish journal of microbiology. 2017;(1):9-15
Abstract
The composition of the oral microbiome in healthy individuals is complex and dynamic, and depends on many factors, such as anatomical location in the oral cavity, diet, oral hygiene habits or host immune responses. It is estimated at present that worldwide about 2 billion people suffer from diseases of the oral cavity, mainly periodontal disease and dental caries. Importantly, the oral microflora involved in local infections may spread and cause systemic, even life-threatening infections. In search for etiological agents of infections in dentistry, traditional approaches are not sufficient, as about 50% of oral bacteria are not cultivable. Instead, metagenomic analyses are particularly useful for studies of the complex oral microbiome - both in healthy individuals, and in patients with oral and dental diseases. In this paper we review the current and future applications of metagenomic studies in evaluation of both the composition of the oral microbiome as well as its potential pathogenic role in infections in dentistry.
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[Recent advances in the field of oral bacteriology].
Shoji, M, Takeshita, T, Maruyama, F, Inaba, H, Imai, K, Kawada-Matsuo, M
Nihon saikingaku zasshi. Japanese journal of bacteriology. 2015;(2):333-8
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Abstract
The oral cavity is inhabited by more than 600 bacterial species; these species compete for nutrients or coexist in order to survive along with the indigenous population. Extreme conditions are prevalent in the oral cavity, and these conditions are influenced by our immunity and variations in nutrition, temperature, and pH. Pathogens that cause dental caries or periodontal disease can survive in these extreme environments; these pathogens are virulent and can cause several diseases. Therefore, research on oral bacteriology is warranted to analyze the virulence factors of these bacteria as well as to ascertain environmental stress responses, interactions between bacteria and human immunity, comparisons of bacterial genomes, and oral microflora. In this review, we provide new data in the fields of bacteriology, immunology, and genomics and describe recent advances in the field of oral bacteriology.
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Systemic immunity shapes the oral microbiome and susceptibility to bisphosphonate-associated osteonecrosis of the jaw.
Kalyan, S, Wang, J, Quabius, ES, Huck, J, Wiltfang, J, Baines, JF, Kabelitz, D
Journal of translational medicine. 2015;:212
Abstract
BACKGROUND Osteonecrosis of the jaw (ONJ) is a rare but serious adverse drug effect linked to long-term and/or high-dose exposure to nitrogen-bisphosphonates (N-BP), the standard of care for the treatment of bone fragility disorders. The mechanism leading to bisphosphonate-associated ONJ (BAONJ) is unclear and optimal treatment strategies are lacking. Recent evidence suggests that BAONJ may be linked to drug-induced immune dysfunction, possibly associated with increased susceptibility to infections in the oral cavity. The objective of this investigation was to comprehensively assess the relationship linking immune function, N-BP exposure, the oral microbiome and ONJ susceptibility. METHODS Leukocyte gene expression of factors important for immunity, wound healing and barrier function were assessed by real-time quantitative PCR and the oral microbiome was characterized by 454 pyrosequencing of the 16S rRNA gene in 93 subjects stratified by N-BP exposure and a history of ONJ. RESULTS There were marked differences in the systemic expression of genes regulating immune and barrier functions including RANK (p = 0.007), aryl hydrocarbon receptor (AHR, p < 0.001), and FGF9 (p < 0.001), which were collectively up-regulated in individuals exposed to N-BP without ONJ relative to treatment controls. In contrast, the expression levels of these same genes were significantly down-regulated in those who had experienced BAONJ. Surprisingly, the oral microbiome composition was not directly linked to either BAONJ or N-BP exposure, rather the systemic leukocyte expression levels of RANK, TNFA and AHR each explained 9% (p = 0.04), 12% (p = 0.01), and 7% (p = 0.03) of the oral bacterial beta diversity. CONCLUSIONS The oral microbiome is unlikely causative of ONJ, rather individuals with BAONJ lacked immune resiliency which impaired their capacity to respond adequately to the immunological stress of N-BP treatment. This may be the common factor linking N-BP and anti-RANK agents to ONJ in at-risk individuals. Preventive and/or therapeutic strategies should target the wound healing deficits present in those with ONJ.