scholarly journals GAS6 is a key homeostatic immunological regulator of host–commensal interactions in the oral mucosa

2017 ◽  
Vol 114 (3) ◽  
pp. E337-E346 ◽  
Author(s):  
Maria Nassar ◽  
Yaara Tabib ◽  
Tal Capucha ◽  
Gabriel Mizraji ◽  
Tsipora Nir ◽  
...  
Keyword(s):  
Critical Role ◽  
Anaerobic Bacteria ◽  
Anaerobic Respiration ◽  
Protein S ◽  
Primary Response ◽  
Oral Epithelium ◽  
Oral Microbiota ◽  
Microbial Dysbiosis ◽  
Mucosal Homeostasis ◽  
Activity Of Enzymes

The oral epithelium contributes to innate immunity and oral mucosal homeostasis, which is critical for preventing local inflammation and the associated adverse systemic conditions. Nevertheless, the mechanisms by which the oral epithelium maintains homeostasis are poorly understood. Here, we studied the role of growth arrest specific 6 (GAS6), a ligand of the TYRO3–AXL–MERTK (TAM) receptor family, in regulating oral mucosal homeostasis. Expression of GAS6 was restricted to the outer layers of the oral epithelium. In contrast to protein S, the other TAM ligand, which was constitutively expressed postnatally, expression of GAS6 initiated only 3–4 wk after birth. Further analysis revealed that GAS6 expression was induced by the oral microbiota in a myeloid differentiation primary response gene 88 (MyD88)-dependent fashion. Mice lacking GAS6 presented higher levels of inflammatory cytokines, elevated frequencies of neutrophils, and up-regulated activity of enzymes, generating reactive nitrogen species. We also found an imbalance in Th17/Treg ratio known to control tissue homeostasis, as Gas6-deficient dendritic cells preferentially secreted IL-6 and induced Th17 cells. As a result of this immunological shift, a significant microbial dysbiosis was observed in Gas6−/− mice, because anaerobic bacteria largely expanded by using inflammatory byproducts for anaerobic respiration. Using chimeric mice, we found a critical role for GAS6 in epithelial cells in maintaining oral homeostasis, whereas its absence in hematopoietic cells synergized the level of dysbiosis. We thus propose GAS6 as a key immunological regulator of host–commensal interactions in the oral epithelium.

scholarly journals Oral microbial dysbiosis and its performance in predicting oral cancer

2020 ◽  
Author(s):  
Shih-Chi Su ◽  
Lun-Ching Chang ◽  
Hsien-Da Huang ◽  
Chih-Yu Peng ◽  
Chun-Yi Chuang ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Fusobacterium Nucleatum ◽  
Risky Behaviors ◽  
Health Condition ◽  
Oral Microbiome ◽  
Oral Microbiota ◽  
Microbial Dysbiosis ◽  
Anti Cancer ◽  
Betel Quid Chewing ◽  
Male Patients

Abstract Dysbiosis of oral microbiome may dictate the progression of oral squamous cell carcinoma (OSCC). Yet, the composition of oral microbiome fluctuates by saliva and distinct sites of oral cavity and is affected by risky behaviors (smoking, drinking and betel quid chewing) and individuals’ oral health condition. To characterize the disturbances in the oral microbial population mainly due to oral tumorigenicity, we profiled the bacteria within the surface of OSCC lesion and its contralateral normal tissue from discovery (n = 74) and validation (n = 42) cohorts of male patients with cancers of the buccal mucosa. Significant alterations in the bacterial diversity and relative abundance of specific oral microbiota (most profoundly, an enrichment for genus Fusobacterium and the loss of genus Streptococcus in the tumor sites) were identified. Functional prediction of oral microbiome shown that microbial genes related to the metabolism of terpenoids and polyketides were differentially enriched between the control and tumor groups, indicating a functional role of oral microbiome in formulating a tumor microenvironment via attenuated biosynthesis of secondary metabolites with anti-cancer effects. Furthermore, the vast majority of microbial signatures detected in the discovery cohort was generalized well to the independent validation cohort, and the clinical validity of these OSCC-associated microbes was observed and successfully replicated. Overall, our analyses reveal signatures (a profusion of Fusobacterium nucleatum CTI-2 and a decrease in Streptococcus pneumoniae) and functions (decreased production of tumor-suppressive metabolites) of oral microbiota related to oral cancer.

scholarly journals The usual anaerobic bacterial suspects extracted from a global metagenomic database of Covid19 patients from Peru, Cambodia, China, Brazil and the US - Prevotella, Veillonella, Capnocytophaga, Fusobacterium, Oribacterium and Bacteroides should be monitored for colonization

2020 ◽  
Author(s):  
Sandeep Chakraborty
Keyword(s):  
Anaerobic Bacteria ◽  
Anaerobic Respiration ◽  
Clinical Results ◽  
Cellular Level ◽  
Heme Binding ◽  
Sequencing Data ◽  
The Us ◽  
Hemoglobin Degradation ◽  
Mitochondrial Cytochrome Oxidase ◽  
Different Parts

The Covid19 pandemic [1], triggered by novel strain of a coronavirus SARS-Cov2 [2] has spread globally like a wildfire [3] after being first detected in Wuhan.Previous studies from China, Brazil and the US:Previously, several sequencing datasets - some of them published [4–9], others having sequencing data sub- mitted in NCBI (with no associated publications) [10–13] - have revealed the metagenome in these patients from different parts of the world. The overwhelming presence of anaerobic bacteria (very low concentration of oxygen kills them) in these patients has led to the theory that antibiotics (like doxycycline/Metronidazole) targeting these specific organisms may provide better clinical results [14].Two more studies added - patients from Peru and Cambodia:Here, two more studies from Peru (Table 1) and Cambodia (Table 2) provide further corroboration to the anaerobic bacteria theory. These anaerobic bacteria have virtually colonized the metagenome - pushing other aerobic species out of the niche, disrupting the homeostasis. Around 30% and 23% of the reads from Peru and Cambodia are bacterial, respectively. This is not observed in other patients, even when having chronic issues [15].Common opportunistic anaerobic bacteria in this global metagenomic Covid19 datasetHere, I enumerate common opportunistic anaerobic bacteria present in this global metagenomic Covid19 dataset (Table 3). Any or multiple of these might become the main colonizer after SARS-Cov2 infection in Covid19. The trigger of such an event is still elusive. However, once this happens, some of these bacte- ria express hemoglobin degrading proteins [16], heme-binding proteins sequestering heme after hemoglobin degradation [17], ‘plundering‘ iron, and thereby sequestering oxygen [18]. Hypoxia could also result from formate, the by-product of anaerobic respiration, which inhibits mitochondrial cytochrome oxidase, causing hypoxia at the cellular level [19].

scholarly journals Effect of Ligilactobacillus salivarius and Other Natural Components against Anaerobic Periodontal Bacteria

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4519
Author(s):  
Marzena Kucia ◽  
Ewa Wietrak ◽  
Mateusz Szymczak ◽  
Paweł Kowalczyk
Keyword(s):  
Alveolar Bone ◽  
Anaerobic Bacteria ◽  
Drug Susceptibility ◽  
Diffusion Method ◽  
In Vitro Tests ◽  
Growth Media ◽  
Oral Microbiota ◽  
Disk Diffusion Method

In this present study, the bacteriostatic effect of Salistat SGL03 and the Lactobacillus salivarius strain contained in it was investigated in adults in in vivo and in vitro tests on selected red complex bacteria living in the subgingival plaque, inducing a disease called periodontitis, i.e., chronic periodontitis. Untreated periodontitis can lead to the destruction of the gums, root cementum, periodontium, and alveolar bone. Anaerobic bacteria, called periopathogens or periodontopathogens, play a key role in the etiopathogenesis of periodontitis. The most important periopathogens of the oral microbiota are: Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and others. Our hypothesis was verified by taking swabs of scrapings from the surface of the teeth of female hygienists (volunteers) on full and selective growth media for L. salivarius. The sizes of the zones of growth inhibition of periopathogens on the media were measured before (in vitro) and after consumption (in vivo) of Salistat SGL03, based on the disk diffusion method, which is one of the methods of testing antibiotic resistance and drug susceptibility of pathogenic microorganisms. Additionally, each of the periopathogens analyzed by the reduction inoculation method, was treated with L. salivarius contained in the SGL03 preparation and incubated together in Petri dishes. The bacteriostatic activity of SGL03 preparation in selected periopathogens was also analyzed using the minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests. The obtained results suggest the possibility of using the Salistat SGL03 dietary supplement in the prophylaxis and support of the treatment of periodontitis—already treated as a civilization disease.

scholarly journals Identification of Vaginal Microbial Communities Associated with Extreme Cervical Shortening in Pregnant Women

2020 ◽  
Vol 9 (11) ◽  
pp. 3621
Author(s):  
Monica Di Paola ◽  
Viola Seravalli ◽  
Sara Paccosi ◽  
Carlotta Linari ◽  
Astrid Parenti ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Microbial Communities ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Anaerobic Bacteria ◽  
Vaginal Microbiota ◽  
Rrna Gene ◽  
Spontaneous Preterm Birth ◽  
Short Cervix ◽  
Lactobacillus Spp

The vaginal microbiota plays a critical role in pregnancy. Bacteria from Lactobacillus spp. are thought to maintain immune homeostasis and modulate the inflammatory responses against pathogens implicated in cervical shortening, one of the risk factors for spontaneous preterm birth. We studied vaginal microbiota in 46 pregnant women of predominantly Caucasian ethnicity diagnosed with short cervix (<25 mm), and identified microbial communities associated with extreme cervical shortening (≤10 mm). Vaginal microbiota was defined by 16S rRNA gene sequencing and clustered into community state types (CSTs), based on dominance or depletion of Lactobacillus spp. No correlation between CSTs distribution and maternal age or gestational age was revealed. CST-IV, dominated by aerobic and anaerobic bacteria different than Lactobacilli, was associated with extreme cervical shortening (odds ratio (OR) = 15.0, 95% confidence interval (CI) = 1.56–14.21; p = 0.019). CST-III (L. iners-dominated) was also associated with extreme cervical shortening (OR = 6.4, 95% CI = 1.32–31.03; p = 0.02). Gestational diabetes mellitus (GDM) was diagnosed in 10/46 women. Bacterial richness was significantly higher in women experiencing this metabolic disorder, but no association with cervical shortening was revealed by statistical analysis. Our study confirms that Lactobacillus-depleted microbiota is significantly associated with an extremely short cervix in women of predominantly Caucasian ethnicity, and also suggests an association between L. iners-dominated microbiota (CST III) and cervical shortening.

scholarly journals Control of Nipah Virus Infection in Mice by the Host Adaptors Mitochondrial Antiviral Signaling Protein (MAVS) and Myeloid Differentiation Primary Response 88 (MyD88)

2019 ◽  
Vol 221 (Supplement_4) ◽  
pp. S401-S406 ◽  
Author(s):  
Mathieu Iampietro ◽  
Noemie Aurine ◽  
Kevin P Dhondt ◽  
Claire Dumont ◽  
Rodolphe Pelissier ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Critical Role ◽  
Nipah Virus ◽  
Primary Response ◽  
Myeloid Differentiation ◽  
Type I ◽  
Antiviral Signaling ◽  
Signaling Protein ◽  
Mitochondrial Antiviral Signaling ◽  
Mitochondrial Antiviral Signaling Protein

Abstract Interferon (IFN) type I plays a critical role in the protection of mice from lethal Nipah virus (NiV) infection, but mechanisms responsible for IFN-I induction remain unknown. In the current study, we demonstrated the critical role of the mitochondrial antiviral signaling protein signaling pathway in IFN-I production and NiV replication in murine embryonic fibroblasts in vitro, and the redundant but essential roles of both mitochondrial antiviral signaling protein and myeloid differentiation primary response 88 adaptors, but not toll/interleukin-1 receptor/resistance [TIR] domain–containing adaptor–inducing IFN-β (TRIF), in the control of NiV infection in mice. These results reveal potential novel targets for antiviral intervention and help in understanding NiV immunopathogenesis.

scholarly journals Alzheimer's disease and periodontitis - an elusive link

2014 ◽  
Vol 60 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Abhijit N. Gurav
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Critical Role ◽  
Anaerobic Bacteria ◽  
Systemic Infection ◽  
Low Grade ◽  
Inflammatory Status ◽  
Pro Inflammatory Cytokines

Alzheimer's disease is the preeminent cause and commonest form of dementia. It is clinically characterized by a progressive descent in the cognitive function, which commences with deterioration in memory. The exact etiology and pathophysiologic mechanism of Alzheimer's disease is still not fully understood. However it is hypothesized that, neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient inflammatory features, characterized by microglial activation and escalation in the levels of pro-inflammatory cytokines in the affected regions. Studies have suggested a probable role of systemic infection conducing to inflammatory status of the central nervous system. Periodontitis is common oral infection affiliated with gram negative, anaerobic bacteria, capable of orchestrating localized and systemic infections in the subject. Periodontitis is known to elicit a "low grade systemic inflammation" by release of pro-inflammatory cytokines into systemic circulation. This review elucidates the possible role of periodontitis in exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect the onset and progression of Alzheimer's disease. Periodontitis shares the two important features of Alzheimer's disease namely oxidative damage and inflammation, which are exhibited in the brain pathology of Alzheimer's disease. Periodontitis can be treated and hence it is a modifiable risk factor for Alzheimer's disease.

scholarly journals Syk Plays a Critical Role in the Expression and Activation of IRAK1 in LPS-Treated Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jae Gwang Park ◽  
Young-Jin Son ◽  
Byong Chul Yoo ◽  
Woo Seok Yang ◽  
Ji Hye Kim ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Critical Role ◽  
Primary Response ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Treatment Conditions ◽  
Lps Treatment

To address how interleukin-1 receptor-associated kinase 1 (IRAK1) is controlled by other enzymes activated by toll-like receptor (TLR) 4, we investigated the possibility that spleen tyrosine kinase (Syk), a protein tyrosine kinase that is activated at an earlier stage during TLR4 activation, plays a central role in regulating the functional activation of IRAK1. Indeed, we found that overexpression of myeloid differentiation primary response gene 88 (MyD88), an adaptor molecule that drives TLR signaling, induced IRAK1 expression and that piceatannol, a Syk inhibitor, successfully suppressed the MyD88-dependent upregulation of IRAK1 under LPS treatment conditions. Interestingly, in Syk-knockout RAW264.7 cells, IRAK1 activity was almost completely blocked after LPS treatment, while providing a Syk-recovery gene to the knockout cells successfully restored IRAK1 expression. According to our measurements of IRAK1 mRNA levels, the transcriptional upregulation of IRAK1 was induced by LPS treatment between 4 and 60 min, and this can be suppressed in Syk knockout cells, providing an effect similar that that seen under piceatannol treatment. The overexpression of Syk reverses this effect and leads to a significantly higher IRAK1 mRNA level. Collectively, our results strongly suggest that Syk plays a critical role in regulating both the activity and transcriptional level of IRAK1.

scholarly journals Downregulation of decidual SKP2 is associated with human recurrent miscarriage

2021 ◽  
Author(s):  
Shijian Lv ◽  
Mei Liu ◽  
Lizhen Xu ◽  
Cong Zhang
Keyword(s):  
Stromal Cells ◽  
Recurrent Miscarriage ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Protein S ◽  
Pcr Analysis ◽  
Endometrial Stromal Cells ◽  
Downstream Target ◽  
F Box Protein

Abstract Background: Recurrent miscarriage (RM) is a very frustrating problem for both couples and clinicians. To date, the etiology of RM remains poorly understood. Decidualization plays a critical role in implantation and the maintenance of pregnancy, and its deficiency is closely correlated with RM. The F-box protein S-phase kinase associated protein 2 (SKP2) is a key component of the SCF-type E3 ubiquitin ligase complex, which is critically involved in ErbB family-induced Akt ubiquitination, aerobic glycolysis and tumorigenesis. SKP2 is pivotal for reproduction, and SKP2-deficient mice show impaired ovarian development and reduced fertility.Methods: Here, we investigated the expression and function of SKP2 in human decidualization and its relation with RM. A total of 40 decidual samples were collected. Quantitative PCR analysis, western blot analysis and immunohistochemistry analysis were performed to analyze the differential expression of SKP2 between RM and control cells. For in vitro induction of decidualization, both HESCs (human endometrial stromal cells) cell line and primary ESCs (endometrial stromal cells) were used to analyze the effects of SKP2 on decidualization via siRNA transfection.Results: Compared to normal pregnant women, the expression of SKP2 was reduced in the decidual tissues from individuals with RM. After in vitro induction of decidualization, knockdown of SKP2 apparently attenuated the decidualization of HESCs and resulted in the downregulation of HOXA10 and FOXM1, which are essential for normal human decidualization. Moreover, our experiments demonstrated that SKP2 silencing reduced the expression of its downstream target GLUT1.Conclusions: Our study indicates a functional role of SKP2 in RM: downregulation of SKP2 in RM leads to impaired decidualization and downregulation of GLUT1 and consequently predisposes individuals to RM.

scholarly journals Tumor-Asociated Microbiota in Esophageal Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Weixiong Yang ◽  
Chang-Han Chen ◽  
Minghan Jia ◽  
Xiangbin Xing ◽  
Lu Gao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Critical Role ◽  
Gene Profiling ◽  
Rrna Gene ◽  
Clinical Trial Registry ◽  
Microbial Dysbiosis ◽  
Registration Number

Abstract Background: Human intestinal tract microbiome dysbiosis plays an emerging pivotal role in tumorigenesis of gastrointestinal tract cancers. For esophageal squamous cell carcinoma (ESCC), the esophageal microbiota plays a critical role during the pathogenesis. The microbiome of esophageal can impact its host decades before the onset of ESCC, and can interact with the host’s physiological situation, which are affected by lifestyle factors, including diet, obesity, alcohol and tobacco use, and oral hygiene.Our objective is to analyze the composition of the ESCC-associated microbiota and characterize its contribution to the development of ESCC. The esophageal microbiota was prospectively investigated in 18 patients with ESCC and 11 patients with physiological normal (PN) esophagus by 16S rRNA gene profiling, using next-generation sequencing. Results: The microbiota composition in tumor tissues of ESCC patients is significantly different from that of patients with PN tissues. The ESCC microbiota was characterized by reduced microbial diversity, by decreased abundance of Bacteroidetes, Fusobacteria and Spirochactes. Employing these taxa into a microbial dysbiosis index demonstrated that dysbiosis microbiota had good capacity to discriminate between ESCC and PN esophagus. Functional analysis of the microbiota characterized that ESCC microbiota had altered nitrate reductase and nitrite reductase functions when compared with PN group. The observations were confirmed in other validation cohorts.Conclusions: Detailed analysis of the microbiota of the ESCC patients revealed that tumor exhibit a dysbiotic microbial community when compared with PN groups. We characterized microbial compositional changes, and further identified significant enrichments of Treponema amylovorum, Streptococcus infantis, Prevotella nigrescens, Porphyromonas endodontalis, Veillonella dispar, Aggregatibacter segnis, Prevotella melaninogenica, Prevotella intermedia, Prevotella tannerae, Prevotella nanceiensis and Streptococcus anginosus in ESCC oncogenic progression.Trial registration number: This study was registered at the Chinese Clinical Trial Registry (ChiCTR1800018897). http://www.chictr.org.cn/.

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