The Oral Host-Microbial Interactome: An Ecological Chronometer of Health?

An increasing number of studies reveal that host-microbial interactome networks are coordinated, impacting human health and disease. Recently, several lines of evidence have revealed associations between the acquisition of a complex microbiota and adaptive immunity, supporting that host-microbiota symbiotic relationships have evolved as a means to maintain homeostasis where the role of the microbiota is to promote and educate the immune system. Here, we hypothesize an oral host-microbial interactome that could serve as an ecological chronometer of health and disease, with specific focus on caries, periodontal diseases, and cancer. We also review the current state of the art on the human oral microbiome and its correlations with host innate immunity, and host cytokine control, with the goal of using this information for disease prediction and designing novel treatments for local and systemic dysbiosis. In addition, we discuss new insights into the role of novel host-microbial signals as potential biomarkers, and their relevance for the future of precision dentistry and medicine.

Inflammatory Networks Linking Oral Microbiome with Systemic Health and Disease.

The dance between microbes and the immune system takes place in all biological systems, including the human body, but this interaction is especially complex in the primary gateway to the body: the oral cavity. Recent advances in technology have enabled deep sequencing and analysis of members and signals of these communities. In a healthy state, the oral microbiome is composed of commensals, and their genes and phenotypes may be selected by the immune system to survive in symbiosis. These highly regulated signals are modulated by a network of microbial and host metabolites. However, in a diseased state, host-microbial networks lead to dysbiosis and considerable burden to the host prior to systemic impact that extends beyond the oral compartment. Interestingly, we presented data demonstrating similarities between human and mice immune dysbiosis and discussed how this affects the host response to similar pathobionts. The host and microbial signatures of a number of disease states are currently being examined to identify potential correlations. How the oral microbiome interacts with inflammation and the immune system to cause disease remains an area of active research. In this review, we summarize recent advancements in understanding the role of oral microbiota in mediating inflammation and altering systemic health and disease. In line with these findings, it is possible that existing conditions may be resolved by targeting specific immune-microbial markers in a positive way.

Long-term impact of oral surgery with or without amoxicillin on the oral microbiome-A prospective cohort study.

Routine postoperative antibiotic prophylaxis is not recommended for third molar extractions. However, amoxicillin still continues to be used customarily in several clinical practices worldwide to prevent infections. A prospective cohort study was conducted in cohorts who underwent third molar extractions with (group EA, n = 20) or without (group E, n = 20) amoxicillin (250 mg three times daily for 5 days). Further, a control group without amoxicillin and extractions (group C, n = 17) was included. Salivary samples were collected at baseline, 1-, 2-, 3-, 4-weeks and 3 months to assess the bacterial shift and antibiotic resistance gene changes employing 16S rRNA gene sequencing (Illumina-Miseq) and quantitative polymerase chain reaction. A further 6-month follow-up was performed for groups E and EA. Seven operational taxonomic units reported a significant change from baseline to 3 months for group EA (adjusted p < 0.05). No significant change in relative abundance of bacteria and ß-lactamase resistance genes (TEM-1) was observed over 6 months for any group (adjusted p > 0.05). In conclusion, the salivary microbiome is resilient to an antibiotic challenge by a low-dose regimen of amoxicillin. Further studies evaluating the effect of routinely used higher dose regimens of amoxicillin on gram-negative bacteria and antibiotic resistance genes are warranted.

Knowledge regarding hepatitis B mother-to-child transmission among healthcare workers in South China.

To determine the knowledge regarding hepatitis B virus (HBV) mother-to-child transmission (MTCT) and its prevention and treatment among healthcare workers (HCWs) in Guangdong Province, China, an HBV endemic area. An HBV knowledge questionnaire was administered to 900 HCWs from the 3rd Affiliated Hospital of Sun Yat-Sen University and 2 rural hospitals in Guangdong Province. The 27 items in the questionnaire fell into 3 sections: HBV MTCT general knowledge, respondents' practices of preventing HBV MTCT and awareness of the resources of preventing HBV MTCT. The data collected were coded and analysed using SPSS software version 20. In total, 503 of 900 HCWs responded to the survey (response rate: 55.9%). Eighty-four individuals responded correctly to all of the knowledge questions: 58 were doctors, and 26 were nurses (P < .05). Doctors more often performed practices than nurses (t = 3.591, P < .01). Participants from the infectious disease department demonstrated a significantly higher proportion of correct answers and resource utilization than other specialties (χ2  = 14.052, 7.998, P < .01). In terms of the average knowledge score, t test or ANOVA showed that there were significant differences between the specialty groups (t = 3.110, P < .01), hospital level groups (t = 2.337, P < .05) and age groups (F = 3.020, P < .05). Respondents' initiative increased with hospital level and age (t = 2.993, 7.493, P < .01). A considerable percentage of HCWs has misconceptions about HBV MTCT. Healthcare workers, in particular nurses, those working in noninfectious disease departments or township hospitals and younger medical staff, lack systematic and comprehensive knowledge about HBV MTCT and are in urgent need of HBV-related training.

Draft Genome Sequences of Two Pairs of Human Intestinal Bifidobacterium longum subsp. longum Strains, 44B and 1-6B and 35B and 2-2B, Consecutively Isolated from Two Children after a 5-Year Time Period.

We report the genome sequences of four isolates of a human gut symbiont, Bifidobacterium longum. Strains 44B and 35B were isolated from two 1-year-old infants, while 1-6B and 2-2B were isolated from the same children 5 years later. The sequences permit investigations of factors enabling long-term colonization of bifidobacteria.

A cross-sectional study of hepatitis E virus infection in healthy people directly exposed and unexposed to pigs in a rural community in northern Thailand.

A cross-sectional study of the association between occupational pig exposure and hepatitis E virus (HEV) infection in adult pig farmers and the general population who were not directly exposed to pigs was conducted in Nan Province, Thailand, from November 2010 to April 2011. All participants were interviewed to provide information on their job history, eating habits and other potential confounders. The prevalence of anti-HEV immunoglobulin G antibodies (IgG) among 513 subjects was 23.0%. Hand washing with water and soap was associated with a lower seroprevalence of HEV infection, whereas living in an area with frequent flooding (OR 1.64, 95% CI: 1.00-2.68) and consuming internal pig organs more than twice per week (OR 3.23, 95%CI: 1.15-9.01) were both associated with a higher seroprevalence of anti-HEV IgG. There was no association between HEV seroprevalence and frequent, direct occupational pig contact.

Correlation between mutations in the core and NS5A genes of hepatitis C virus genotypes 1a, 1b, 3a, 3b, 6f and the response to pegylated interferon and ribavirin combination therapy.

Several studies have reported correlation between mutations in core and NS5A proteins of hepatitis C virus (HCV) and response to interferon (IFN) therapy. In particular, mutations in NS5A protein have been shown to correlate with responsiveness to IFN treatment of HCV-1b in Japanese patients. This study investigated whether amino acid (aa) mutations in the core and NS5A proteins of HCV-1a, 1b, 3a, 3b and 6f correlated with the response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy in Thai patients. The entire sequences of core and NS5A of HCV from 76 HCV-infected patients were analysed in comparison with corresponding reference sequences. The data revealed that the number of aa mutations in full-length NS5A, its C-terminus, IFN sensitivity-determining region, variable region 3 (V3) and V3 plus flanking region of HCV-1b NS5A protein were significantly higher in responders than in the treatment failure group (P = 0.010, 0.031, 0.046, 0.020 and 0.006, respectively). Similar results were found in a putative protein kinase R binding domain region in HCV-6f NS5A protein (P = 0.022). Moreover, specific aa substitutions in NS5A that appeared to be associated with responders or the treatment failure group were observed at positions 78 and 305 for HCV-1b (P = 0.028), 64 and 52 for HCV-1a (P = 0.033) and 6f (P = 0.045). Nevertheless, analysis of aa sequences of core protein revealed highly conserved sequences among HCV genotypes and no significant differences between the viruses from responders and the treatment failure group. Our findings indicate that mutations in aa residues of NS5A of HCV-1a, 1b and 6f correlated well with responsiveness to Peg-IFN and RBV combination therapy.

Using DGGE profiling to develop a novel culture medium suitable for oral microbial communities.

More than 700 bacterial species have been detected in the human oral cavity. They form highly organized microbial communities and are responsible for many oral infectious diseases, such as dental caries and periodontal disease. The prevention and treatment of these diseases require a comprehensive knowledge of oral microbial communities, which largely relies on culture-dependent methods to provide detailed phenotypic and physiological analysis of these communities. However, most of the currently available laboratory media can only selectively support the growth of a limited number of bacterial species within these communities, and fail to sustain the original oral microbial diversity. In this study, using denaturing gradient gel electrophoresis (DGGE) as an index to systematically survey and analyse the selectivity of commonly used laboratory media, we developed a new medium (SHI medium) by combining the ingredients of several selected media that can support different subpopulations within the original oral microbial community derived from pooled saliva. DGGE and 454 pyrosequencing analysis showed that SHI medium was capable of supporting a more diversified community with a microbial profile closer to that of the original oral microbiota. Furthermore, 454 pyrosequencing revealed that SHI medium supported the growth of many oral species that have not before been cultured. Crystal violet assay and the confocal laser scanning microscope analysis indicated that, compared with other media, SHI medium is able to support a more complex saliva-derived biofilm with higher biomass yield and more diverse species. This DGGE-guided method could also be used to develop novel media for other complex microbial communities.

Kinetics of conjugative gene transfer on surfaces in granular porous media.

The transfer of genetic material among bacteria in the environment can occur both in the planktonic and attached state. Given the propensity of organisms to exist in sessile microbial communities in oligotrophic subsurface conditions, and that such conditions typify the subsurface, this study focuses on exploratory modeling of horizontal gene transfer among surface-associated Escherichiacoli in the subsurface. The mathematics so far used to describe the kinetics of conjugation in biofilms are developed largely from experimental observations of planktonic gene transfer, and are absent of lags or plasmid stability that appear experimentally. We develop a model and experimental system to quantify bacterial filtration and gene transfer in the attached state, on granular porous media. We include attachment kinetics described in Nelson et al. (2007) using the filtration theory approach of Nelson and Ginn (2001, 2005) with motility of E. coli described according to Biondi et al. (1998).

HIV vaccine preparedness studies in the non-organization for economic co-operation and development (non-OECD) countries.

HIV vaccine development remains an urgent priority. Vaccine preparedness studies to assess feasibility are an important precursor to HIV vaccine trials. Studies such as these have taken place in many non-Organization for Economic Co-operation and Development (non-OECD) countries using diverse cohorts. This article is a systematic review of retention rates and willingness to participate (WTP) in HIV vaccine trials. Studies took place in Brazil, the Democratic Republic of Congo, Haiti, India, Russia, Thailand, and several sub-Saharan African countries. Studies generally reported recruitment of high-risk individuals. Of 33 studies we identified, retention was assessed in 16 studies, and the 12-month retention ranged from 77 to 85%. Willingness to participate was assessed in 21 studies. Willingness to participate ranged from 23 to 100%, and increased knowledge was associated with an increased WTP. Vaccine preparedness studies have taken place using diverse cohorts in the non-OECD countries. In general, retention rates and WTP have been adequate to conduct HIV vaccine trials. Educational programs to improve knowledge about HIV vaccines may contribute to better follow-up and an increased WTP in these countries.

Genomic differences between Fibrobacter succinogenes S85 and Fibrobacter intestinalis DR7, identified by suppression subtractive hybridization.

Fibrobacter is a highly cellulolytic genus commonly found in the rumen of ruminant animals and cecum of monogastric animals. In this study, suppression subtractive hybridization was used to identify the genes present in Fibrobacter succinogenes S85 but absent from F. intestinalis DR7. A total of 1,082 subtractive clones were picked, plasmids were purified, and inserts were sequenced, and the clones lacking homology to F. intestinalis were confirmed by Southern hybridization. By comparison of the sequences of the clones to one another and to those of the F. succinogenes genome, 802 sequences or 955 putative genes, comprising approximately 409 kb of F. succinogenes genomic DNA, were identified that lack similarity to those of F. intestinalis chromosomal DNA. The functional groups of genes, including those involved in cell envelope structure and function, energy metabolism, and transport and binding, had the largest number of genes specific to F. succinogenes. Low-stringency Southern hybridization showed that at least 37 glycoside hydrolases are shared by both species. A cluster of genes responsible for heme, porphyrin, and cobalamin biosynthesis in F. succinogenes S85 was either missing from or not functional in F. intestinalis DR7, which explains the requirement of vitamin B12 for the growth of the F. intestinalis species. Two gene clusters encoding NADH-ubiquinone oxidoreductase subunits probably shared by Fibrobacter genera appear to have an important role in energy metabolism.

The genome of Salinibacter ruber: convergence and gene exchange among hyperhalophilic bacteria and archaea.

Saturated thalassic brines are among the most physically demanding habitats on Earth: few microbes survive in them. Salinibacter ruber is among these organisms and has been found repeatedly in significant numbers in climax saltern crystallizer communities. The phenotype of this bacterium is remarkably similar to that of the hyperhalophilic Archaea (Haloarchaea). The genome sequence suggests that this resemblance has arisen through convergence at the physiological level (different genes producing similar overall phenotype) and the molecular level (independent mutations yielding similar sequences or structures). Several genes and gene clusters also derive by lateral transfer from (or may have been laterally transferred to) haloarchaea. S. ruber encodes four rhodopsins. One resembles bacterial proteorhodopsins and three are of the haloarchaeal type, previously uncharacterized in a bacterial genome. The impact of these modular adaptive elements on the cell biology and ecology of S. ruber is substantial, affecting salt adaptation, bioenergetics, and photobiology.

Knowledge, attitude and practice survey regarding blood donation in a Northwestern Chinese city.

Recruitment of low-risk blood donors in developing countries is challenging. We studied the attitudes towards blood donation in several populations in a city in Western China. A survey of knowledge, attitude and practice was performed including 1280 individuals from eight distinct populations in Urumqi, Xinjiang Uyghur Autonomous Region, China. Included were Han Chinese and Uyghur populations of blood donors, non-donors, injection drug users, students and factory workers. Knowledge about blood donation varied between the groups. Factors motivating blood donation included social pressure, desire to know screening results and altruism. Inhibiting factors included fear of contracting an infection and other adverse health effects, including loss of vitality. Misconceptions about the effects of blood donation are widespread, even among educated persons in Urumqi. Fear of acquiring a serious infection may have been increased by the reports of HIV acquisition during plasma donations in China.

INH preventive therapy among adult HIV-infected patients in Thailand.

SETTING: Two HIV/AIDS clinics in Bangkok. OBJECTIVE: Although isoniazid (INH) preventive therapy (IPT) can reduce the risk of active TB among HIV-infected individuals, preventive therapy is rarely used in developing countries. The WHO recommends INH prophylaxis for tuberculin skin test (TST) positive HIV positives or for all HIV positives in countries with a high prevalence of latent TB if TST is unfeasible. It is not known whether IPT without TST will affect adherence. DESIGN: Prior to receiving IPT, 914 HIV-infected patients in Bangkok were randomized to TST or not. Adherence, measured by self-report and pill counts, and proportion completing therapy were evaluated. RESULTS: Adherence was 84.5% and 79.7%, by self-report, and 81.8% and 73.9% by pill count, respectively, in PPD-positive and non-TST-screened subjects (adjusted OR 1.44, 95%CI 0.79-2.64 and 1.53, 95%CI 0.45-5.26). The drop-out rate before treatment was 6.3% in the TST-screened and 1.7% in the non-TST screened subjects (OR 3.93, 95%CI 1.18-16.04). CONCLUSION: TST screening was not a predictor of adherence to IPT once therapy began, but it was associated with a higher drop-out rate prior to therapy. Acceptable levels of adherence were observed with both regimens.

HIV-1 subtype E progression among northern Thai couples: traditional and non-traditional predictors of survival.

BACKGROUND: In the continuing effort to introduce antiretroviral therapy in resource-limited settings, there is a need to understand differences between natural history of HIV in different populations and to identify feasible clinical measures predictive of survival. METHODS: We examined predictors of survival among 836 heterosexuals who were infected with HIV subtype CRF01_AE in Thailand. RESULTS: From 1993 to 1999, 269 (49.4%) men and 65 (25.7%) women died. The median time from the estimated seroconversion to death was 7.8 years (95% confidence interval 7.0-9.1). Men and women with enrolment CD4 counts <200 cells/microl had about 2 and 11 times greater risk of death than those with CD4 counts of 200-500 and >500, respectively. Measurements available in resource-limited settings, including total lymphocyte count (TLC), anaemia, and low body mass index (BMI), also predicted survival. Men with two or more of these predictors had a median survival of 0.8 (0.5-1.8) years, compared with 2.7 (1.9-3.3) years for one predictor and 4.9 (4.1-5.2) years for no predictors. CONCLUSIONS: The time from HIV infection to death appears shorter among this Thai population than among antiretroviral naive Western populations. CD4 count and viral load (VL) were strong, independent predictors of survival. When CD4 count and VL are unavailable, individuals at high risk for shortened HIV survival may be identified by a combination of low TLC, anaemia, and low BMI. This combination of accessible clinical measures of the disease stage may be useful for medical management in resource-limited settings.

The effect of light exercise upon blood flow velocity determined by laser-Doppler flowmetry.

PRIMARY OBJECTIVE: The dominant, 0.1 Hz frequency, Traube-Hering component of blood flow velocity, which is related to baroreflex activity, may be modulated through the established techniques of manipulative medicine. Light exercise programmes, appropriate for use by the elderly and collectively termed gymnastique douce, also are believed to impact the baroreflex in a positive manner. Our objective was to test the relationship between the Traube-Hering oscillation and light exercise. METHODS: Using laser-Doppler flowmetry to quantify the Traube-Hering and other components of the blood flow velocity oscillation, we compared flowmetry records of 10 subjects before and immediately following a light-exercise programme. RESULTS: The data show that the light exercise programme amplifies the 0.1 Hz component of the blood flowmetry record. CONCLUSIONS: The 0.1 Hz component of blood-flow velocity is physiologically linked to baroreflex activity. It is this component that is augmented by a light exercise programme.

HIV incidence and risk behaviours after voluntary HIV counselling and testing (VCT) among adults aged 19-35 years living in peri-urban communities around Chiang Mai city in northern Thailand, 1999.

The Thai government began HIV voluntary counselling and testing (VCT) in all provinces in 1992. We evaluated HIV incidence after participants utilized VCT and its effect on risk behaviours among northern Thai adults aged 19-35 years. A total of 924 men and 1,327 women volunteered to participate in the study. Subjects were counseled, interviewed (socio-demographic, HIV risk behaviour, and HIV testing history), and tested for HIV infection at baseline and at 6 months follow-up. All participants were provided group pre-test counselling; HIV test results were provided in individual confidential post-test counselling. Overall, 329 of 391 men and 621 of 669 women who reported a prior HIV test before participating in our study reported negative results at the previous test. Of these, nine men and 13 women tested positive at baseline, giving incidence rates of 1.04 and 0.69 per 100 person years (PY), respectively. Recent risk behaviour was rare; as a result, the effects of VCT on risk behaviours among the study participants could not be determined. The HIV incidence after VCT among this study population is substantial. Studies to investigate factors associated with HIV incidence among VCT clients could provide insights for more effective HIV prevention.