Association between periodontal disease due to Campylobacter rectus and cerebral microbleeds in acute stroke patients.

Oral health conditions and cerebral small vessel disease, such as white matter lesions or cerebral microbleeds (CMBs), are associated with the incidence of stroke. The purpose of this study was to examine the associations between oral health conditions (serum IgG titers of periodontal pathogens) with the presence or severity of CMBs in acute stroke patients. From January 2013 to April 2016, acute stroke patients were registered in two hospitals. Serum samples were evaluated for antibody titers against 9 periodontal pathogens using the ELISA method. The cut-off points for reactivity (the positive decision point) to each antigen were defined as more than a mean ELISA unit + 1 standard deviation (after logarithmic transformation) in all subjects. CMBs were evaluated on T2*-weighted MRI. In all, 639 patients were evaluated (ischemic, n = 533 and hemorrhagic, n = 106; 73.1 ± 12.9 years old). Among these patients, 627 were available for CMB evaluation. Among the 9 evaluated periodontal pathogens, only Campylobacter rectus (C. rectus) was associated with the presence of CMBs. the prevalence of positive serum antibody titers against C. rectus was higher among patients with CMBs than among those without CMBs (14.6% vs. 8.7%, P = 0.025). In addition, positive serum antibody titers against C. rectus remained one of the factors associated with the presence of CMBs in multivariate logistic analysis (odds ratio 2.03, 95% confidence interval 1.19-3.47, P = 0.010). A positive serum antibody titer against C. rectus was associated with the presence of CMBs in acute stroke patients.

Impact of the use of Kampo medicine in patients with esophageal cancer during chemotherapy:a clinical trial for oral hygiene and oral condition.

OBJECTIVE: The aim of this study was to investigate the impact of the use of two Kampo medicines on oral mucositis, tongue coating bacteria, and gingiva condition in patients with esophageal cancer undergoing chemotherapy. METHODS: Twenty-three esophageal cancer patients who receive chemotherapy at Tokushima University Hospital, were included. The participants, who received professional oral healthcare, were randomly divided into three groups:7 subjects received Daiokanzoto sherbets, 7 subjects received Hangeshashinto sherbets, and 9 subjects received nothing (control). The numbers of total bacteria and specific periodontopathogenic bacteria in tongue coating were determined in addition to clinical parameters. RESULTS: No difference on the onset of oral mucositis was found among the three groups. However, tongue coating index, gingival index (GI), plaque index, the number of total bacteria, Fusobacterium nucleatum and Campylobacter rectus were decreased during chemotherapy. More specifically, GI as well as the number of F. nucleatum and C. rectus were decreased significantly in the Daiokanzoto group when compared to the control group (psize 8 < 0.05). No such differences were observed for the group receiving Hangeshashinto. CONCLUSION: This clinical trial showed that Daiokanzoto might be effective in attenuating gingival inflammation and reducing the levels of periodontopathogenic bacteria in patients with esophageal cancer. J. Med. Invest. 65:184-190, August, 2018.

TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.

Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. Although the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, six being classical pathogens and four putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone-marrow-derived macrophages (BMDM) from wild-type (WT) and Toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. Campylobacter concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2 stimulatory activity. These studies allowed us to provide important evidence on newly identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855).

Periodontal disease bacteria specific to tonsil in IgA nephropathy patients predicts the remission by the treatment.

BACKGROUND: Immunoglobulin (Ig)A nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse. METHODS AND FINDINGS: We made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062). Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012). Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002). Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019). There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046), and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037) by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy. CONCLUSION: This insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

Subgingival microbial consortia and the clinical features of periodontitis in adolescents.

This study aimed to investigate the association between microbial consortia and the clinical features of periodontitis using a multilevel modeling approach. A total of 958 sites in 87 adolescents with periodontitis (cases) and 73 controls were microbiologically sampled and clinically examined. Associations between each of the clinical parameters clinical attachment, probing depth, supragingival plaque, calculus, bleeding on probing, and each of 18 bacterial species; and between the same clinical parameters and each of two microbial consortia identified, were investigated using mixed-effects regression modeling. Higher counts of Tannerella forsythia, Campylobacter rectus, and Porphyromonas gingivalis were all statistically significantly associated with higher values of clinical attachment level, probing depth, and bleeding on probing in the sampled site, when both case status and between-subject variance were accounted for. Higher counts for the consortium comprising the putative periodontopathogens were statistically significantly associated in a dose-response manner with both higher clinical attachment levels and with increased pocket depth. The counts for the consortium predominantly comprising the early-colonizer species were statistically significantly negatively associated with the presence of supragingival calculus, but positively associated with the presence of supragingival plaque. The study demonstrates a relationship between the counts of putative periodontopathogens and clinical attachment levels and probing pocket depths, even for low levels of these clinical parameters.

Altered gene expression in murine placentas in an infection-induced intrauterine growth restriction model: a microarray analysis.

The biological mechanisms leading to incomplete intrauterine growth are not completely elucidated and few studies have investigated infection-mediated growth restriction. In this investigation we report the alterations induced by maternal infectious challenge in placental gene expression patterns using a murine model. Pregnant dams were challenged at day E7.5 with the oral human pathogen Campylobacter rectus to elicit fetal growth restriction. At embryonic day E16.5 placentas were collected to compare placental gene expression patterns from normal fetuses of unchallenged dams and growth restricted fetuses from infected dams. Differential gene expression patterns were determined using Agilent Oligo array (G4121A) with a false discovery rate of P<0.05 and pathway analyses were performed. Seventy-four genes were differentially expressed during infection-mediated growth restriction with 9 genes significantly up-regulated, indicating that the effects of maternal infection on gene expression were predominantly suppressive. Pathway analyses indicated that 46 of the 65 genes that were significantly down-regulated were associated with placental/fetal development, and 26 of those were imprinted genes. Among the 9 genes that were up-regulated, 4 are involved in oxygen supply to the fetus and the development of the vascular system. Microarray analysis demonstrated that in the pregnant mouse model, maternal infection that induced growth restriction was associated with down-regulated placental expression of critical growth and developmental related genes, including many imprinted genes. These findings may have significant implications for our understanding of the mechanisms underlying infection-associated human fetal growth restriction and the role of differential placental expression of imprinted genes in fetal growth.

Characterization of the invasive and inflammatory traits of oral Campylobacter rectus in a murine model of fetoplacental growth restriction and in trophoblast cultures.

Campylobacter species (C. jejuni, C. fetus) are enteric abortifacient bacteria in humans and ungulates. Campylobacter rectus is a periodontal pathogen associated with human fetal exposure and adverse pregnancy outcomes including preterm delivery. Experiments in pregnant mice have demonstrated that C. rectus can translocate from a distant site of infection to the placenta to induce fetal growth restriction and impair placental development. However, placental tissues from human, small-for-gestational age deliveries have not been reported to harbor C. rectus despite evidence of maternal infection and fetal exposure by fetal IgM response. This investigation examined the temporal relationship between the placental translocation of C. rectus and the effects on fetal growth in mice. BALB/c mice were infected at gestational day E7.5 to examine placental translocation of C. rectus by immunohistology. C. rectus significantly decreased fetoplacental weight at E14.5 and at E16.5. C. rectus was detected in 63% of placentas at E14.5, but not at E16.5. In in vitro trophoblast invasion assays, C. rectus was able to effectively invade human trophoblasts (BeWo) but not murine trophoblasts (SM9-1), and showed a trend for more invasiveness than C. jejuni. C. rectus challenge significantly upregulated both mRNA and protein levels of IL-6 and TNFalpha in a dose-dependent manner in human trophoblasts, but did not increase cytokine expression in murine cells, suggesting a correlation between invasion and cytokine activation. In conclusion, the trophoblast-invasive trait of C. rectus that appears limited to human trophoblasts may play a role in facilitating bacterial translocation and placental inflammation during early gestation.

Prevalence of periodontopathic bacteria in aggressive periodontitis patients in a Chilean population.

BACKGROUND: Actinobacillus actinomycetemcomitans is considered a major etiologic agent of aggressive periodontitis (AgP). Other periodontopathic bacteria such as Porphyromonas gingivalis are also suspected of participating in aggressive periodontitis although the evidence to support this is controversial. The aim of the present study was to determine the prevalence of eight periodontopathic bacteria in Chilean patients with AgP. METHODS: Subgingival plaque samples were collected from 36 aggressive, 30 localized, and six generalized periodontitis patients. Samples from 17 advanced chronic periodontitis (CP) patients were taken as controls. Samples collected from the four deepest periodontal pockets in each patient were pooled in prereduced transport fluid (RTF) and cultured. Periodontal bacteria were primarily identified by colony morphology under stereoscopic microscope and rapid biochemical tests. The identity of some bacterial isolates was confirmed by colony polymerase chain reaction (PCR). RESULTS: AgP showed a significatively higher prevalence of C. rectus than CP (P = 0.036). The only statistical difference found was for C. rectus. Patients with AgP showed a higher, but not statistically significant, prevalence of P. gingivalis, E. corrodens, P. micros, and Capnocytophaga sp. A similar prevalence in both groups of patients was observed for F. nucleatum and P. intermedia/nigrescens, and A. actinomycetemcomitans was less prevalent in AgP than CP patients. In localized AgP, P. intermedia/nigrescens, E. corrodens, F. nucleatum, and P. micros were the more prevalent pathogens in contrast to generalized AgP patients who harbored A. actinomycetemcomitans, P. gingivalis, and Capnocytophaga sp. as the most prevalent bacteria. CONCLUSIONS: C. rectus, P. gingivalis, E. corrodens, P. micros, and Capnocytophaga sp. were the most predominant periodontopathic bacteria of AgP in this Chilean population, but the only statistical difference found here between AgP and CP was for C. rectus, suggesting that the differences in clinical appearance may be caused by factors other than the microbiological composition of the subgingival plaque of these patients. In this study, the prevalence of A. actinomycetemcomitans was much lower than that of P. gingivalis.

Campylobacter rectus mediates growth restriction in pregnant mice.

BACKGROUND: Recent studies have suggested that subclinical infection may be an important cause of low birth weight. Campylobacters are important human pathogens, causing septicemia and occasionally abortion, premature labor, or severe perinatal infection. The potential role of oral species of Campylobacter in mediating adverse pregnancy outcomes in animal models has not yet been determined. Our objective was to determine the effects of Campylobacter rectus (C. rectus) infection on pregnancy outcomes in a mouse model. METHODS: On embryonic day (E) 7.5, pregnant mice received a subcutaneous, intra-chamber challenge with live C. rectus at concentrations of 0, 10(7) or 10(9) colony forming units (CFU)/ml. They were sacrificed on E 16.5 and fetuses were evaluated for stage of development, weight, and crown-rump length. RESULTS: Dams receiving C. rectus had more fetal resorptions after challenge with 10(7) or 10(9) CFU/ml (24.1% and 30.1%, respectively) than controls (9%). Higher numbers of growth-restricted fetuses were also observed in the C. rectus challenged groups (21%) as compared to controls (2.3%). Fetuses from dams challenged with 10(9) CFU/ml weighed less (0.49 +/- 0.05 g) and had shorter crown-rump lengths (14.69 +/- 0.56 mm) than controls (0.53 +/- 0.04 g; 15.54 +/- 0.63 mm). C. rectus was detected by polymerase chain reaction (PCR) in the placentas from both treated groups and in maternal liver tissues from the 10(9) CFU/ml challenged group. CONCLUSIONS: Remote subcutaneous maternal C. rectus infection increases fetal resorptions and fetal growth restriction in a mouse model. The effects of an oral C. rectus infection on pregnancy remain to be determined.

Enfermedades periodontales y periimplantarias. Factores de riesgo y su diagnóstico / Periodontal and periimplantar diseases. Risk factors and diagnostic

Algunas de las enfermedades de los tejidos que rodean a los dientes y a los implantes oseointegrados son infecciones producidas por una combinación de especies bacterianas que desbordan la capacidad de resistencia de los tejidos. En este sentido, la presencia de las respectivas enfermedades precisa no solamente de la presencia de una flora bacteriana adecuada sino también de una serie de factores de riesgo relacionados con el huésped y ambientales que determinan una respuesta tisular específica. Dentro de estos factores de riesgo deben considerarse, y hay que procurar identificar, si es posible, factores corno la predisposición genética, ciertas enfermedades como la diabetes, el tabaco y la higiene oral. En el caso de la periimplantitis, no existe suficiente evidencia como para determinar tan claramente el papel de los factores de riesgo en su etiología y evolución clínica. Sin embargo, podrían ser similares a los mencionados para la periodontitis (AU)

Infectious diseases of the tissues surrounding teeth and osseointegrated implants are produced by different bacterial species which overcome tissue defense mechanisms. In this regard, different individual as well as environmental risk factors would determine a specific tissue response to plaque accumulation. Some of these periodontal risk factors have been identified so far, e.g. genetic predisposition, diabetes, smoking and oral hygiene. Due to a lack of pertinent scientific evidence, it is difficult to enumerate which risk factors are involved in peri-implantitis, although could be very much similar to those related to periodontitis (AU)

Campylobacter surface-layers (S-layers) and immune evasion.

Many pathogenic bacteria have evolved mechanisms for evading host immune systems. One evasion mechanism is manifest by the surface layer (S-layer), a paracrystalline protein structure composed of S-layer proteins (SLPs). The S-layer, possessed by 2 Campylobacter species (C. fetus and C. rectus), is external to the bacterial outer membrane and can have multiple functions in immune avoidance. C. fetus is a pathogen of ungulates and immunocompromised humans, in whom it causes disseminated bloodstream disease. In C. fetus, the S-layer is required for dissemination and is involved in 2 mechanisms of evasion. First, the S-layer confers resistance to complement-mediated killing in non-immune serum by preventing the binding of complement factor C3b to the C. fetus cell surface. S-layer expressing C. fetus strains remain susceptible to complement-independent killing, utilizing opsonic antibodies directed against the S-layer. However, C. fetus has also evolved a mechanism for avoiding antibody-mediated killing by high-frequency antigenic variation of SLPs. Antigenic variation is accomplished by complex DNA inversion events involving a family of multiple SLP-encoding genes and a single SLP promoter. Inversion events result in the expression of antigenically variant S-layers, which require distinct antibody responses for killing. C. rectus is implicated in the pathogenesis of periodontal disease and also possesses an S-layer that appears to be involved in evading the human system. Although studied less extensively than its C. fetus counterpart, the C. rectus S-layer appears to confer resistance to complement-mediated killing and to cause the down-regulation of proinflammatory cytokines.