Realizing the clinical utility of saliva for monitoring oral diseases.

In the era of personalized/precision health care, additional effort is being expended to understand the biology and molecular mechanisms of disease processes. How these mechanisms are affected by individual genetics, environmental exposures, and behavioral choices will encompass an expanding role in the future of optimally preventing and treating diseases. Considering saliva as an important biological fluid for analysis to inform oral disease detection/description continues to expand. This review provides an overview of saliva as a diagnostic fluid and the features of various biomarkers that have been reported. We emphasize the use of salivary biomarkers in periodontitis and transport the reader through extant literature, gaps in knowledge, and a structured approach toward validating and determine the utility of biomarkers in periodontitis. A summation of the findings support the likelihood that a panel of biomarkers including both host molecules and specific microorganisms will be required to most effectively identify risk for early transition to disease, ongoing disease activity, progression, and likelihood of response to standard periodontal therapy. The goals would be to develop predictive algorithms that serve as adjunctive diagnostic tools which provide the clinician and patient important information for making informed clinical decisions.

Transcriptomic features of programmed and inflammatory cell death in gingival tissues.

The local gingival tissue environment with homeostasis and tissue-destructive events of periodontitis demonstrates major changes in histological features and biology of the oral/sulcular epithelium, fibroblasts, vascular cells, inflammatory cell infiltration, and alveolar bone. OBJECTIVE: This study used an experimental periodontitis model to detail the gingival transcriptome related to cell death processes of pyroptosis, necroptosis, ferroptosis, and cuproptosis. MATERIALS AND METHODS: Healthy Macaca mulatta primates stratified by age, ≤3 years (young), 7-12 years (adolescent), 12-15 years (adult), and 17-23 years (aged), provided gingival tissue biopsies for microarray analysis focused on 257 genes representative of the four cell death processes and bacterial plaque samples for 16S rRNA gene analysis. RESULTS: Age differences in the profiles of gene expression in healthy tissues were noted for cuproptosis, ferroptosis, necroptosis, and pyroptosis. Major differences were then observed with disease initiation, progression, and resolution also related to the age of the animals. Distinct bacterial families/consortia of species were significantly related to the gene expression differences for the cell death pathways. CONCLUSIONS: These results emphasized age-associated differences in the gingival tissue molecular response to changes in the quality and quantity of bacteria accumulating with the disease process reflected in regulated cell death pathways that are both physiological and pathophysiological.

Biomarker panel discriminates diabetics with and without periodontitis pre- and post-therapy.

BACKGROUND AND OBJECTIVE: Biological regulators of periodontal inflammation, collagen degradation, and insulin resistance have not been determined in association with severity of periodontitis and response to periodontal treatment in diabetics. Our objective was to determine whether type 2 diabetes (T2DM) patients with periodontal disease present a distinct salivary biomarker profile compared with T2DM patients without periodontal disease and healthy subjects (without diabetes and periodontitis) pre- and post-nonsurgical therapy. METHODS: Clinical parameters of periodontal health and whole unstimulated saliva were collected from 92 participants (31 Not Periodontitis, NP; 32 T2DM without periodontitis, DWoP; and 29 with T2DM with periodontitis, DWP) at baseline. The T2DM groups received scaling and root planning (SRP) and provided saliva at 6-week follow-up. Salivary concentrations of interleukin (IL)-1ß, IL-6, matrix metalloproteinase-8 (MMP-8), and resistin were measured by immunoassay. RESULTS: The DWP group had significantly more disease and higher salivary concentrations at baseline for IL-1ß, MMP-8, and resistin (p's < .01) compared with DWoP and NP. SRP resulted in significant improvement in periodontal parameters for the T2DM groups; however, more disease persisted (p < .001), and IL-1ß, MMP-8, and resistin concentrations remained significantly higher in the DWP than the DWoP group (p < .01) at 6 weeks post-treatment. Principal component analysis demonstrated the DWoP group appeared more biologically similar to the NP group than the DWP group. Concentrations of these salivary biomarkers increased with increasing periodontal disease severity (p < .05) in this study population. CONCLUSION: Salivary concentrations of IL-1ß, MMP-8, and resistin appear to serve as biomarkers of periodontal status pre- and post-treatment, irrespective of diabetes status.

Sex effects on gingival transcriptomic patterns during initiation, progression, and resolution of periodontitis.

BACKGROUND: The prevalence and severity of periodontitis demonstrates altered population distribution with age, sex, and race and ethnicity. While males exhibit greater frequency of disease, particularly with aging, the underlying basis for this observation remains obscure. OBJECTIVE: This study used a nonhuman primate (Macaca mulatta) model of experimental ligature-induced periodontitis in adult animals to evaluate gingival transcriptomic differences stratified based upon sex of the animal. METHODS: The 18 animals represented humans ages 40-80 years, with gingival tissue samples obtained at baseline, 0.5 months (initiation), 1 and 3 months (progression), and at 5 months that were 60 days after ligature removal for clinical disease resolution. Microarray analysis was used to quantify gene expression profiles in the gingival tissues. RESULTS: The results demonstrated clear gene expression differences in healthy (baseline) tissues between the sexes, with elevations in females associated with immune responses and elevation in males related to tissue structural genes. With disease initiation, fewer genes differed between the sexes, while these differences were significantly increased in progressing disease and resolution, particularly in male animals. Overexpressed biological processes showed tissue structural/functional genes at initiation, with host response pathways altered during disease progression. Resolution samples generally demonstrated biological processes of cellular metabolism that differed from baseline healthy samples. CONCLUSION: The transcriptomic findings support sex as a biological variable in periodontitis using a nonhuman primate model of experimental periodontitis.

Dietary Strawberries Improve Serum Metabolites of Cardiometabolic Risks in Adults with Features of the Metabolic Syndrome in a Randomized Controlled Crossover Trial.

Dietary strawberries have been shown to improve cardiometabolic risks in multiple clinical trials. However, no studies have reported effects on serum metabolomic profiles that may identify the target pathways affected by strawberries as underlying mechanisms. We conducted a 14-week randomized, controlled crossover study in which participants with features of metabolic syndrome were assigned to one of the three arms for four weeks separated by a one-week washout period: control powder, 1 serving (low dose: 13 g strawberry powder/day), or 2.5 servings (high dose: 32 g strawberry powder/day). Blood samples, anthropometric measures, blood pressure, and dietary and physical activity data were collected at baseline and at the end of each four-week phase of intervention. Serum samples were analyzed for primary metabolites and complex lipids using different mass spectrometry methods. Mixed-model ANOVA was used to examine differences in the targeted metabolites between treatment phases, and LASSO logistic regression was used to examine differences in the untargeted metabolites at end of the strawberry intervention vs. the baseline. The findings revealed significant differences in the serum branched-chain amino acids valine and leucine following strawberry intervention (high dose) compared with the low-dose and control phases. Untargeted metabolomic profiles revealed several metabolites, including serum phosphate, benzoic acid, and hydroxyphenyl propionic acid, that represented improved energy-metabolism pathways, compliance measures, and microbial metabolism of strawberry polyphenols, respectively. Thus, dietary supplementation of strawberries significantly improves the serum metabolic profiles of cardiometabolic risks in adults.

Differential oral microbiome in nonhuman primates from periodontitis-susceptible and periodontitis-resistant matrilines.

Rhesus monkeys (n = 36) exhibiting a healthy periodontium at baseline were used to induce progressing periodontitis through ligature placement around premolar/molar teeth. Bacterial samples were collected at baseline, 0.5, 1, and 3 months of disease and at 5 months for disease resolution. The animals were distributed into two groups (18/group): 3-7 years (young) and 12-23 years (adult) and stratified based upon matriline susceptibility to periodontitis (PDS, susceptible; PDR, resistant). A total of 444 operational taxonomic units (OTUs) with 100 microbes representing a core microbiome present in ≥75% of the samples were identified. Only 48% of the major phylotypes overlapped in the PDS and PDR samples. Different OTU abundance patterns were seen in young animals from the PDS and PDR matrilines, with qualitative similarities during disease and the relative abundance of phylotypes becoming less diverse. In adults, 23 OTUs were increased during disease in PDS samples and 24 in PDR samples; however, only five were common between these groups. Greater diversity of OTU relative abundance at baseline was observed with adult compared to young oral samples from both the PDS and PDR groups. With disease initiation (2 weeks), less diversity of relative abundance and some distinctive increases in specific OTUs were noted. By 1 month, there was considerable qualitative homogeneity in the major OTUs in both groups; however, by 3 months, there was an exacerbation of both qualitative and quantitative differences in the dominant OTUs between the PDS and PDR samples. These results support that some differences in disease expression related to matriline (familial) periodontitis risk may be explained by microbiome features.

Gingival transcriptomic patterns of macrophage polarization during initiation, progression, and resolution of periodontitis.

Phenotypic and functional heterogeneity of macrophages is clearly a critical component of their effective functions in innate and adaptive immunity. This investigation hypothesized that altered profiles of gene expression in gingival tissues in health, disease, and resolution would reflect changes in macrophage phenotypes occurring in these tissues. The study used a nonhuman primate model to evaluate gene expression profiles as footprints of macrophage variation using a longitudinal experimental model of ligature-induced periodontitis in animals from 3 to 23 years of age to identify aging effects on the gingival environment. Significant differences were observed in distribution of expressed gene levels for M0, M1, and M2 macrophages in healthy tissues with the younger animals showing the least expression. M0 gene expression increased with disease in all but the aged group, while M1 was increased in adult and young animals, and M2 in all age groups, as early as disease initiation (within 0.5 months). Numerous histocompatibility genes were increased with disease, except in the aged samples. An array of cytokines/chemokines representing both M1 and M2 cells were increased with disease showing substantial increases with disease initiation (e.g. IL1A, CXCL8, CCL19, CCL2, CCL18), although the aged tissues showed a more limited magnitude of change across these macrophage genes. The analytics of macrophage genes at sites of gingival health, disease, and resolution demonstrated distinct profiles of host response interactions that may help model the disease mechanisms occurring with the formation of a periodontal lesion.

The Associations of Cardiometabolic and Dietary Variables with Clinical Periodontitis in Adults with and without Type 2 Diabetes: A Cross-Sectional Study.

Periodontitis is a commonly occurring inflammatory oral disease affecting a large proportion of global and US adults and is characterized by the destruction of the tooth-supporting apparatus. Its etiology is multifactorial, and type 2 diabetes and diet play critical roles in its remission and progression. However, few studies have addressed nutritional and serum vitamin D status in adults with periodontitis in the presence of diabetes. A cross-sectional study (n = 78), and a sub-set of age- and BMI-matched case-control studies (n = 50), were conducted to examine differences in dietary and cardiometabolic variables, and serum vitamin D in adults with periodontitis with or without diabetes. Participants provided fasting blood samples and 24-h diet recalls on at least two different days. Data on health history, body weight, height, nutritional habits, and clinical features of periodontitis were also collected. The Mann-Whitney U Test (with exact p-value estimation by Monte Carlo simulation) was used to examine differences by diabetes status in continuous and ordinal variables. Results revealed significantly lower serum vitamin D, and dietary intake of fruits, vegetables, dairy, vitamins A and C in adults with periodontitis with vs. without diabetes in the sub-study (all p < 0.05). In the overall sample, adults with diabetes presented with higher caries risk measures and lower numbers of teeth than those without diabetes; plaque and bleeding scores did not differ by diabetes status. Finally, a significant associations of food habits was observed, especially consuming protein-rich foods twice a day with a lower bleeding score, and daily consumption of fried or fast foods with a fewer number of teeth present (all p < 0.05). The present findings show significant dietary and serum vitamin D inadequacies among adults with periodontitis, and diabetes further aggravates the observed malnourishment and oral health.

Mucosal circadian rhythm pathway genes altered by aging and periodontitis.

As circadian processes can impact the immune system and are affected by infections and inflammation, this study examined the expression of circadian rhythm genes in periodontitis. METHODS: Macaca mulatta were used with naturally-occurring and ligature-induced periodontitis. Gingival tissue samples were obtained from healthy, diseased, and resolved sites in four groups: young (≤3 years), adolescent (3-7 years), adult (12-26) and aged (18-23 years). Microarrays targeted circadian rhythm (n = 42), inflammation/tissue destruction (n = 11), bone biology (n = 8) and hypoxia pathway (n = 7) genes. RESULTS: The expression of many circadian rhythm genes, across functional components of the pathway, was decreased in healthy tissues from younger and aged animals, as well as showing significant decreases with periodontitis. Negative correlations of the circadian rhythm gene levels with inflammatory mediators and tissue destructive/remodeling genes were particularly accentuated in disease. A dominance of positive correlations with hypoxia genes was observed, except HIF1A, that was uniformly negatively correlated in health, disease and resolution. CONCLUSIONS: The chronic inflammation of periodontitis exhibits an alteration of the circadian rhythm pathway, predominantly via decreased gene expression. Thus, variation in disease expression and the underlying molecular mechanisms of disease may be altered due to changes in regulation of the circadian rhythm pathway functions.

Immunoglobulin gene expression profiles and microbiome characteristics in periodontitis in nonhuman primates.

Colonization of mucosal tissues throughout the body occurs by a wide array of bacteria in the microbiome that stimulate the cells and tissues, as well as respond to changes in the local milieu. A feature of periodontitis is the detection of adaptive immune responses to members of the oral microbiome that show specificity and changes with disease and treatment. Thus, variations in antibody responses are noted across the population and affected by aging, albeit, data are still unclear as to how these differences relate to disease risk and expression. This study used a nonhuman primate model of experimental periodontitis to track local microbiome changes as they related to the use and expression of a repertoire of immunoglobulin genes in gingival tissues. Gingival tissue biopsies from healthy tissues and following ligature-placement for disease initiation and progression provided gene expression analysis. Additionally, following removal of the ligatures, clinical healing occurs with gene expression in disease resolved tissues. Groups of 9 animals (young: <3 yrs., adolescent: 3-7 yrs., adult -12 to 15 yrs.; aged: 17-22 yrs) were used in the investigation. In healthy tissues, young and adolescent animals showed levels of expression of 78 Ig genes that were uniformly less than adults. In contrast, ⅔ of the Ig genes were elevated by > 2-fold in the aged samples. Specific increases in an array of the Ig gene transcripts were detected in adults at disease initiation and throughout progression, while increases in young and adolescent animals were observed only with disease progression, and in aged samples primarily late in disease progression. Resolved lesions continued to demonstrate elevated levels of Ig gene expression in only young, adolescent and adult animals. The array of Ig genes significantly correlated with inflammatory, tissue biology and hypoxia genes in the gingival tissues, with variations associated with age. In the young group of animals, specific members of the oral microbiome positively correlated with Ig gene expression, while in the older animals, many of these correlations were negative. Significant correlations were observed with a select assortment of bacterial OTUs and multiple Ig genes in both younger and older animal samples, albeit the genera/species showed little overlap. Incorporating this array of microbes and host responses clearly discriminated the various time points in transition from health to disease and resolution in both the young and adult animals. The results support a major importance of adaptive immune responses in the kinetics of periodontal lesion formation, and support aging effects on the repertoire of Ig genes that may relate to the increased prevalence and severity of periodontitis with age.

Comparative Analysis of Gene Expression Patterns for Oral Epithelial Cell Functions in Periodontitis.

The structure and function of epithelial cells are critical for the construction and maintenance of intact epithelial surfaces throughout the body. Beyond the mechanical barrier functions, epithelial cells have been identified as active participants in providing warning signals to the host immune and inflammatory cells and in communicating various detailed information on the noxious challenge to help drive specificity in the characteristics of the host response related to health or pathologic inflammation. Rhesus monkeys were used in these studies to evaluate the gingival transcriptome for naturally occurring disease samples (GeneChip® Rhesus Macaque Genome Array) or for ligature-induced disease (GeneChip® Rhesus Gene 1.0 ST Array) to explore up to 452 annotated genes related to epithelial cell structure and functions. Animals were distributed by age into four groups: ≤ 3 years (young), 3-7 years (adolescent), 12-16 years (adult), and 18-23 years (aged). For naturally occurring disease, adult and aged periodontitis animals were used, which comprised 34 animals (14 females and 20 males). Groups of nine animals in similar age groups were included in a ligature-induced periodontitis experiment. A buccal gingival sample from either healthy or periodontitis-affected tissues were collected, and microarray analysis performed. The overall results of this investigation suggested a substantial alteration in epithelial cell functions that occurs rapidly with disease initiation. Many of these changes were prolonged throughout disease progression and generally reflect a disruption of normal cellular functions that would presage the resulting tissue destruction and clinical disease measures. Finally, clinical resolution may not signify biological resolution and represent a continued risk for disease that may require considerations for additional biologically specific interventions to best manage further disease.

Gingival tissue antibody gene utilization in aging and periodontitis.

OBJECTIVE: This study used a nonhuman primate model of ligature-induced periodontitis to document the characteristics of immunoglobulin (Ig) gene usage in gingival tissues with disease and affected by age. BACKGROUND: Adaptive immune responses to an array of oral bacteria are routinely detected in local gingival tissues and the systemic circulation across the human population. The level and diversity of antibody increases with periodontitis, reflecting the increased quantity of B cells and plasmacytes in the tissues at sites of periodontal lesions. METHODS: Macaca mulatta (n = 36) in four groups (young - ≤3 years; adolescent >3-7 years; adult - 12-15 years; aged - 17-23 years) were used in this study. Gingival tissues were sampled at baseline (health), 2 weeks (initiation), 1 and 3 months (progression), and 5 months (resolution) of the lesion development and transcriptomic analysis included 78 Ig-related genes. RESULTS: The results demonstrated extensive variation in Ig gene usage patterns and changes with the disease process that was substantially affected by the age of the animal. Of note was that the aged animals generally demonstrated elevated expression on multiple Ig genes even in the baseline/healthy gingival tissues. The expression levels revealed 5 aggregates of Ig gene change profiles across the age groups. The number of gene changes were greatly increased in adult animals with the initiation of disease, while the young and adolescent animals showed extensive changes with disease progression. Elevated Ig gene transcripts remained with disease resolution except in the aged animals. The response profiles demonstrated selective heavy/light change gene transcripts that differed with age and clustering of the transcript expression was dominated by the age of the animals. CONCLUSIONS: The results suggested potential critical variations in the molecular aspects of Ig gene expression in gingival tissues that can contribute to understanding the kinetics of periodontal lesions, as well as the variation in episodes, rapidity of progression, and role in resolution that are impacted by age.

Gingival Transcriptome of Innate Antimicrobial Factors and the Oral Microbiome With Aging and Periodontitis.

The epithelial barrier at mucosal sites comprises an important mechanical protective feature of innate immunity, and is intimately involved in communicating signals of infection/tissue damage to inflammatory and immune cells in these local environments. A wide array of antimicrobial factors (AMF) exist at mucosal sites and in secretions that contribute to this innate immunity. A non-human primate model of ligature-induced periodontitis was used to explore characteristics of the antimicrobial factor transcriptome (n = 114 genes) of gingival biopsies in health, initiation and progression of periodontal lesions, and in samples with clinical resolution. Age effects and relationship of AMF to the dominant members of the oral microbiome were also evaluated. AMF could be stratified into 4 groups with high (n = 22), intermediate (n = 29), low (n = 18) and very low (n = 45) expression in healthy adult tissues. A subset of AMF were altered in healthy young, adolescent and aged samples compared with adults (e.g., APP, CCL28, DEFB113, DEFB126, FLG2, PRH1) and were affected across multiple age groups. With disease, a greater number of the AMF genes were affected in the adult and aged samples with skewing toward decreased expression, for example WDC12, PGLYRP3, FLG2, DEFB128, and DEF4A/B, with multiple age groups. Few of the AMF genes showed a >2-fold increase with disease in any age group. Selected AMF exhibited significant positive correlations across the array of AMF that varied in health and disease. In contrast, a rather limited number of the AMF significantly correlated with members of the microbiome; most prominent in healthy samples. These correlated microbes were different in younger and older samples and differed in health, disease and resolution samples. The findings supported effects of age on the expression of AMF genes in healthy gingival tissues showing a relationship to members of the oral microbiome. Furthermore, a dynamic expression of AMF genes was related to the disease process and showed similarities across the age groups, except for low/very low expressed genes that were unaffected in young samples. Targeted assessment of AMF members from this large array may provide insight into differences in disease risk and biomolecules that provide some discernment of early transition to disease.

Streptococcus gordonii-Induced miRNAs Regulate CCL20 Responses in Human Oral Epithelial Cells.

The mechanisms through which oral commensal bacteria mitigates uncontrolled inflammatory responses of the oral mucosa remain unknown. Here, we show that representative oral bacterial species normally associated with oral health [S. gordonii (Sg), V. parvula (Vp), A. naeslundii (An), C. sputigena (Cs), and N. mucosa (Nm)] enhanced differential chemokine responses in oral epithelial cells (OECs), with some bacteria (An, Vp, and Nm) inducing higher chemokine levels (CXCL1, CXCL8) than others (Sg, Cs). Although all bacterial species (except Cs) increased CCL20 mRNA levels consistent with protein elevations in cell lysates, only An, Vp, and Nm induced higher CCL20 secretion, similar to the effect of the oral pathogen F. nucleatum (Fn). In contrast, most CCL20 remained associated with OECs exposed to Sg and negligible amounts released into the cell supernatants. Consistently, Sg attenuated An-induced CCL20. MiR-4516 and miR-663a were identified as Sg-specifically induced miRNAs modulating validated targets of chemokine-associated pathways. Cell transfection with miR-4516 and miR-663a decreased An- and Fn-induced CCL20. MiRNA upregulation and attenuation of An-induced CCL20 by Sg were reversed by catalase. Up-regulation of both miRNAs was specifically enhanced by oral streptococci H2O2-producers. These findings suggest that CCL20 levels produced by OECs in response to bacterial challenge are regulated by Sg-induced miR-4516 and miR-663a in a mechanism that involves hydrogen peroxide. This type of molecular mechanism could partly explain the central role of specific oral streptococcal species in balancing inflammatory and antimicrobial responses given the critical role of CCL20 in innate (antimicrobial) and adaptive immunity (modulates Th17 responses).

Associations of Diet with Cardiometabolic and Inflammatory Profiles in Pregnant Women at Risk for Metabolic Complications.

Dietary intakes play an important role in the development of metabolic complications during pregnancy. While reported observational studies reveal an inverse association of healthy diets with weight gain, gestational diabetes, and hypertensive complications during pregnancy, there is a paucity of studies conducted among women of specific ethnicities vulnerable to higher risks of pregnancy complications. This is a secondary cross sectional analysis using baseline data from a previously reported clinical trial. We aim to identify associations of maternal habitual dietary intakes with cardiometabolic risks and inflammatory profiles in primarily African American (AA) and Hispanic women in the first half of pregnancy. Fifty-two women met the study criteria and anthropometric, clinical, and dietary data were obtained at baseline. Linear regression analysis was used to determine associations after covariate adjustments. Among the maternal dietary nutrient intakes, total fats were positively associated with maternal body weight, BMI, and serum CRP (ß ± SE: 0.25 ± 0.13, 0.28 ± 0.18, and 0.29 ± 0.14, respectively, all p < 0.05), and saturated fats were positively associated with glycated hemoglobin (0.32 ± 0.12). Dietary fiber intake showed a consistent inverse association with body weight (-0.26 ± 0.13), BMI (-0.19 ± 0.15), glycated hemoglobin (-0.22 ± 0.16), as well as serum CRP (-0.19 ± 0.14). Among the maternal food group intakes, dairy intake was inversely associated with systolic blood pressure (-0.18 ± 0.15) and serum IL-6 (-0.22 ± 0.17), and vegetable intake showed an inverse association with serum CRP (-0.17 ± 0.12) all in adjusted analyses (all p < 0.05). Thus, maternal diet modifications, especially decreasing fats and increasing fiber and dairy may help address obesity and inflammation leading to pregnancy complications in AA and Hispanic women.

Dietary Strawberries Improve Biomarkers of Antioxidant Status and Endothelial Function in Adults with Cardiometabolic Risks in a Randomized Controlled Crossover Trial.

Strawberries, a popularly consumed berry fruit, are rich in bioactive compounds with antioxidant effects. In this study, we examined the effects of two dietary achievable doses of strawberries on the antioxidant status and biomarkers of endothelial function in adults with features of metabolic syndrome and a confirmed low baseline of fruit and vegetable intake. In a 14-week randomized controlled crossover study, participants were assigned to one of three groups for four weeks separated by a one-week washout period: control powder, one serving (low dose: 13 g strawberry powder/day), or 2.5 servings (high dose: 32 g strawberry powder/day). Blood samples and health data were collected at baseline and at the end of each four-week phase of intervention. Thirty-three participants completed all three phases of the trial. Significant increases were observed in serum antioxidant capacity and superoxide dismutase activity as well as decreases in lipid peroxidation after both low and high dose strawberry phases when compared with the control phase. Significant decreases were also observed in soluble vascular cell adhesion molecule-1 and tumor necrosis factor-α with the high dose strawberry phase. These data confirm that consuming strawberries for four weeks significantly improves antioxidant status, endothelial function, and inflammation in adults with cardiometabolic risks.

Dietary Blueberry and Soluble Fiber Improve Serum Antioxidant and Adipokine Biomarkers and Lipid Peroxidation in Pregnant Women with Obesity and at Risk for Gestational Diabetes.

Pregnancies affected by obesity are at high risk for developing metabolic complications with oxidative stress and adipocyte dysfunction contributing to the underlying pathologies. Few studies have examined the role of dietary interventions, especially those involving antioxidants including polyphenolic flavonoids found in fruits and vegetables on these pathologies in high-risk pregnant women. We conducted an 18 gestation-week randomized controlled trial to examine the effects of a dietary intervention comprising of whole blueberries and soluble fiber vs. control (standard prenatal care) on biomarkers of oxidative stress/antioxidant status and adipocyte and hormonal functions in pregnant women with obesity (n = 34). Serum samples were collected at baseline (<20 gestation weeks) and at the end of the study period (32-26 gestation weeks). Study findings showed maternal serum glutathione and antioxidant capacity to be significantly increased, and malondialdehyde to be decreased in the dietary intervention vs. control group (all p < 0.05). Among the adipokine biomarkers, serum plasminogen activator inhibitor-1 and visfatin, as biomarkers of adipocyte dysfunction and insulin resistance, were also decreased following dietary intervention (all p < 0.05). These findings support the need for supplementing maternal diets with berries and fiber to improve oxidative stress and risks of metabolic complications during pregnancy.

Variations in IgG antibody subclass responses to oral bacteria: Effects of periodontal disease and modifying factors.

BACKGROUND AND OBJECTIVE: Local and systemic IgG antibodies or oral bacteria have been described with periodontitis. We extended these observations by assessing the impact of a range of intrinsic factors on serum IgG subclass antibodies to both commensal and pathogenic oral bacteria that would contribute to variations in immune protection or disease susceptibility in periodontitis have not been described. METHODS: Subjects (n = 278) were classified as healthy, gingivitis, or periodontitis and categorized as mild, moderate, and severe periodontitis. Demographic stratification included sex, age, race/ethnicity, smoking, and obesity. Whole formalin-fixed bacteria were used as antigens to detect serum immunoglobulin (Ig)G subclass antibody levels using an ELISA. RESULTS: The greatest differences in variations in IgG subclasses occurred in periodontitis versus health or gingivitis to bacteria considered oral pathogens (eg, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola) with IgG1, IgG2, and IgG4 increased by three- to sevenfold with Pg. Differences in subclass levels and distribution were also observed related to disease severity, particularly related to individual subclass responses to Pg. Examination of the overall population showed that females had elevated antibody, reflected by elevated IgG2 amounts/proportions. The older group of subjects demonstrated elevated antibody to multiple oral bacteria, lacking any particular subclass pattern. IgG2 antibody to Aa and Pg was increased in smokers. Multiple IgG subclass antibody levels to oral pathogens were significantly decreased in the obese subset within this population. CONCLUSION: This investigation identified patterns of IgG subclass antibody responses to oral bacteria and demonstrated substantial effects of disease impacting the level and subclass distribution of antibody to an array of oral bacteria. Altered subclass antibody profiles most often in IgG2 levels and for antibody to P. gingivalis were found related to sex, age, disease severity, race/ethnicity, smoking, and obesity to both pathogens and commensal bacteria.