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BackgroundEpigenetic age, a robust marker of biological aging, has been associated with obesity, low-grade inflammation and metabolic diseases. However, few studies have examined associations between different epigenetic age measures and risk of lung cancer, despite great interest in finding biomarkers to assist in risk stratification for lung cancer screening.MethodsA nested case-control study of lung cancer from the CLUE II cohort study was conducted using incidence density sampling with 1:1 matching of controls to lung cancer cases (n=208 matched pairs). Prediagnostic blood samples were collected in 1989 (CLUE II study baseline) and stored at −70°C. DNA was extracted from buffy coat and DNA methylation levels were measured using Illumina MethylationEPIC BeadChip Arrays. Three epigenetic age acceleration (i.e., biological age is greater than chronological age) measurements (Horvath, Hannum and PhenoAge) were examined in relation to lung cancer risk using conditional logistic regression.ResultsWe did not observe associations between the three epigenetic age acceleration measurements and risk of lung cancer overall; however, inverse associations for the two Hannum age acceleration measures (intrinsic and extrinsic) were observed in men and among younger participants, but not in women or older participants. We did not observe effect modification by time from blood draw to diagnosis.ConclusionFindings from this study do not support a positive association between three different biological age acceleration measures and risk of lung cancer. Additional studies are needed to address whether epigenetic age is associated with lung cancer in never smokers.

Background Although gut fungi have been implicated in the immunopathogenesis of inflammatory bowel disease, the fungal microbiome has not been deeply explored across endohistologic activity and treatment exposure in ulcerative colitis. Methods We analyzed data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry. We evaluated the fungal composition of fecal samples from 98 patients with ulcerative colitis across endoscopic activity (n = 43), endohistologic activity (n = 41), and biologic exposure (n = 82). Across all subgroups, we assessed fungal diversity and differential abundance of taxonomic groups. Results We identified 500 unique fungal amplicon sequence variants across the cohort of 82 patients, dominated by phylum Ascomycota. Compared with endoscopic remission, patients with endoscopic activity had increased Saccharomyces (log2 fold change = 4.54; adjusted P Conclusions Endoscopic inflammation in ulcerative colitis is associated with an expansion of Saccharomyces and Candida compared with remission. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in ulcerative colitis should be evaluated.

AimOur goal was to investigate individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood.Materials and MethodsFor this analysis, we included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at visit 4 and had available data on DNA methylation. DNA methylation levels were compared by periodontal disease severity and edentulism to identify differentially methylated regions (DMRs) and evaluate the CpGs belonging to those DMRs using multinominal logistic regression.ResultsWe identified a region in geneZFP57(6p22.1) that was significantly hypomethylated in severe periodontal disease compared to no/mild periodontal disease in European American participants. A separate region in an unknown gene (located in Chr10: 743,992-744,958) demonstrated significant positive association with edentulism compared to no/mild periodontal disease in African American participants. Four CpGs in a region located withinHOXA4were significantly hypermethylated in severe periodontal disease compared to no/mild periodontal disease in African American participants.ConclusionsOur study highlights epigenetic variations inZPF57andHOXA4that were significantly and reproducibly associated with periodontitis. Future studies should evaluate gene regulatory mechanisms in the candidate regions of these loci.CLINICAL RELEVANCEScientific Rationale for StudyWithout altering the DNA sequence, epigenetic effects (e.g., DNA methylation changes) can alter gene activity and influence host response to periodontal infections. Our well-powered study investigates individual susceptibility to periodontitis by conducting a thorough assessment of periodontitis-related DNA methylation levels in blood.Principal FindingsWe identified two gene regions,ZPF57andHOXA4, that are differentially methylated in individuals with compared to those without periodontitis.Practical implicationsStudying differential leukocyte DNA methylation patterns may point to candidate regions and underlying gene regulatory mechanisms that play a key role in the progression and/or susceptibility to periodontitis.

BACKGROUND The fungal mycobiome has been increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD). Circulating antibodies to Saccharomyces antibodies are detected in 60-70% of Crohn’s disease and in 10-15% of patients with ulcerative colitis (UC). Specific fungal species, including Candida albicans, are increased in active IBD compared to healthy controls. Recently, UC patients with high fecal Candida prior to fecal microbial transplantation (FMT) were more likely to demonstrate robust treatment responses to transplant, with low Candida levels post-FMT predicting ameliorated inflammation in the recipient. Despite the accumulation of findings supporting the role of fungi in IBD, the mycobiome remains poorly characterized in UC. Few studies have examined changes in the UC mycobiome with respect to validated endoscopic indices or histologic parameters; furthermore, the effects of treatment exposure, including biologic medications, on fungal communities in UC are unknown. AIMS In this study, we aim to characterize the fungal mycobiome in UC patients with varying levels of endoscopic activity, endo-histologic activity, and treatment exposure. METHODS We performed a secondary analysis using the data extracted from the Crohn’s and Colitis Foundation’s Study of a Prospective Adult Research Cohort with IBD, which contains clinical, endoscopic, histologic, and metagenomic data. Using Internal Transcribed Spacer based deep sequencing of fungal rDNA from fecal samples, we classified sequences utilizing the UNITE fungal database and a fitted classifier. The R package DESeq2 was used to calculate the log-2 fold change of differential abundance. RESULTS We identified 504 unique fungal amplicon sequence variants across the cohort of 98 patients, belonging to phylum Ascomycota (71.5%), Basidiomycota (11%), Mucoromycota (0.16%), or unidentified (17.2%). Compared to endoscopic remission, patients with endoscopic activity (n=25) were enriched with Saccharomyces (4.31, p< 5 x 10-5) and Candida (2.53, p< 1 x 10-3). Similarly, compared to endo-histologic remission, patients with endo-histologic activity (n=19) were also enriched for Saccharomyces (2.71, p CONCLUSION These data demonstrate that endoscopic and histologic inflammation in UC is associated with expansion of Saccharomyces and Candida compared to remission, even after controlling for exposure to biologic exposure. These findings are recapitulated during endo-histologic activity. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in UC should be evaluated.

BackgroundTo reduce lung cancer burden in the US, a better understanding of biological mechanisms in early disease development could provide new opportunities for risk stratification.MethodsIn a nested case-control study, we measured blood leukocyte DNA methylation levels in pre-diagnostic samples collected from 430 men and women in the 1989 CLUE II cohort. Median time from blood drawn to diagnosis was 14 years for all participants. We compared DNA methylation levels by case/control status to identify novel genomic regions, both single CpG sites and differentially methylated regions (DMRs), while controlling for known DNA methylation changes associated with smoking using a previously described pack-years based smoking methylation score. Stratification analyses were conducted by time from blood draw to diagnosis, histology, and smoking status.ResultsWe identified sixteen single CpG sites and forty DMRs significantly associated with lung cancer risk (q < 0.05). The identified genomic regions were associated with genes including H19, HOXA4, RUNX3, BRICD5, PLXNB2, and RP13. For the single CpG sites, the strongest association was noted for cg09736286 in the DIABLO gene (OR [for 1 SD] = 2.99, 95% CI: 1.95-4.59, P-value = 4.81 × 10−7). For the DMRs, we found that CpG sites in the HOXA4 region were hypermethylated in cases compared to controls.ConclusionThe single CpG sites and DMRs that we identified represented significant measurable differences in lung cancer risk, providing new insights into the biological processes of early lung cancer development and potential biomarkers for lung cancer risk stratification.

Structured AbstractBackgroundPancreatic cancer is projected to become the second leading cause of cancer-related death by 2030 in the United States. DNA methylation (DNAm) age may reflect age-related variations in the biological changes and abnormalities related to cancer development.MethodWe conducted a pooled analysis using prediagnostic blood samples of pancreatic cancer cases and matched controls selected from the Nurses’ Health Study (NHS), the Physician’s Health Study (PHS), and the Health Professionals Follow-up Study (HPFS). We used three DNAm aging clocks (Hannum, Horvath, and PhenoAge) to estimate subjects’ DNAm age, epigenetic age acceleration (AA) and intrinsic epigenetic age acceleration (IEAA) metrics. We performed conditional logistic regression and multivariable Cox proportional hazard regression to examine associations between six AA and IEAA metrics and risk of pancreatic cancer and survival, respectively.ResultsA total of 393 incidence pancreatic cancer cases and 431 matched controls from the NHS, PHS, and HPFS cohorts were included in this analysis. The medians of all three epigenetic AA and three IEAA metrics were consistently above zero (indicating accelerated age) among cases, while they were below zero (indicating decelerated age) among the matched controls. Comparing participants in the highest quartile of age acceleration metrics, the pancreatic cancer risks were significantly increased by 67% to 83% for Hannum and PhenoAge AA or IEAA metrics with minimal of 7- to 9-years accelerated ages. Except for Hovarth AA and IEAA metrics, there were significant dose-response trends, such that higher age accelerations were associated with higher pancreatic cancer risk, but the relationships were nonlinear. Stratified analyses showed heterogeneous associations, varying by participants’ characteristics and by epigenetic AA or IEAA metrics. As time to diagnosis increased, the ORs of pancreatic cancer for the Hannum AA and Horvath AA or IEAA metrics trended upwards, while the ORs for the PhenoAge AA or IEAA and Hannum IEAA metrics trended downward. Overall, we observed no significant association between pancreatic cancer survival and any of the prediagnostic epigenetic AA or IEAA metrics.ConclusionOur results indicate DNAm age acceleration is associated with an increased risk of pancreatic cancer in a nonlinear, dose-response manner. Epigenetic IEAA metrics may be a useful addition to current methods for pancreatic cancer risk prediction.

Summary ParagraphOver eons of co-evolution, the gut microbiota has become an essential organ for humans1,2. However, it is unclear what core members and their ecological organization ensures the stable provision of this organ’s essential health-relevant functions to the host. With high quality metagenome-assembled genomes as network nodes, here we identified two competing guilds3of the most stably and highly connected bacteria that together correlate with a wide range of host health conditions. Genomes in these two guilds kept their ecological relationship unchanged despite experiencing profound abundance changes during a 3-month high fiber intervention and 1-year follow-up in patients with type 2 diabetes (T2DM). The genomes of one guild harbored more genes for plant polysaccharide degradation and butyrate production, while the other guild had more genes for virulence or antibiotic resistance. A Random Forest regression model showed that the abundance distributions of these genomes were associated with 41 out of 43 bio-clinical parameters in the study cohort. With these genomes as reference, Random Forest modeling successfully classified case and control of T2DM, atherosclerotic cardiovascular disease, liver cirrhosis, inflammatory bowel diseases, colorectal cancer, ankylosing spondylitis, schizophrenia, and Parkinson’s disease in 12 independent metagenomic datasets from 1,816 participants across ethnicity and geography. This core microbiome signature may serve as a common target for health recovery.

To review and describe available Knowledge Translation (KT) strategies that are designed for or applied in public health decision-making settings. KT is the exchange, synthesis, and ethically sound application of knowledge. This review proposes that KT strategies in public health settings should be understood as action plans that promote evidence use and facilitate evidence-informed decision-making. This scoping review included studies that reported on KT strategies applied in public health settings, published between 2010 and 2017. Studies were searched using Medline, online KT database, and citation tracing. Data from 305 included studies were synthesized using a coding form and conceptually mapped to identify KT strategies used in public health settings. A total of 124 unique examples of KT methods or tools were identified and summarized into 38 recommended and promising KT strategies. Built on the lists of recommended strategies, this review synthesized a framework that matched all 38 KT strategies to 10 key components of the evidence-informed decision-making process. The public health KT strategies summarized and organized by this review promote a better understanding and more effective use of KT strategies.

Tea flavonoids have been suggested to offer potential benefits to cardiovascular health. This review synthesized the evidence on the relation between tea consumption and risks of cardiovascular disease (CVD) and all-cause mortality among generally healthy adults. PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Food Science and Technology Abstracts, and Ovid CAB Abstract databases were searched to identify English-language publications through 1 November 2019, including randomized trials, prospective cohort studies, and nested case-control (or case-cohort) studies with data on tea consumption and risk of incident cardiovascular events (cardiac or peripheral vascular events), stroke events (including mortality), CVD-specific mortality, or all-cause mortality. Data from 39 prospective cohort publications were synthesized. Linear meta-regression showed that each cup (236.6 mL) increase in daily tea consumption (estimated 280 mg and 338 mg total flavonoids/d for black and green tea, respectively) was associated with an average 4% lower risk of CVD mortality, a 2% lower risk of CVD events, a 4% lower risk of stroke, and a 1.5% lower risk of all-cause mortality. Subgroup meta-analysis results showed that the magnitude of association was larger in elderly individuals for both CVD mortality (n = 4; pooled adjusted RR: 0.89; 95% CI: 0.83, 0.96; P = 0.001), with large heterogeneity (I(2) = 72.4%), and all-cause mortality (n = 3; pooled adjusted RR: 0.92; 95% CI: 0.90, 0.94; P < 0.0001; I(2) = 0.3%). Generally, studies with higher risk of bias appeared to show larger magnitudes of associations than studies with lower risk of bias. Strength of evidence was rated as low and moderate (depending on study population age group) for CVD-specific mortality outcome and was rated as low for CVD events, stroke, and all-cause mortality outcomes. Daily tea intake as part of a healthy habitual dietary pattern may be associated with lower risks of CVD and all-cause mortality among adults.

BackgroundExamining inflammation-related DNA methylation alterations in blood could help elucidate the role of inflammation in lung cancer etiology and aid discovery of factors that are key to lung cancer development and progression. In a nested case-control study, we estimated the neutrophil-to-lymphocyte ratio using a validated index, methylation-derived NLR (mdNLR), and quantified DNA methylation levels at loci previously linked with circulating concentrations of C-reactive protein (CRP). We examined associations between these measures and lung cancer risk, and among the cases, lung cancer survival, using pre-diagnostic blood samples of cases (median of 14 years before diagnosis) and controls in the CLUE I/II cohorts. Our analyses controlled for self-reported smoking and methylation-predicted cumulative smoking in order to better focus our examinations on the DNA methylation marks that are informative of the immune response profile.ResultsUsing conditional logistic regression and further adjusting for BMI, batch effects, and a smoking-based methylation score, we observed a 47% increased risk of non-small cell lung cancer (NSCLC) for one standard deviation increase in mdNLR (n = 150 pairs; OR: 1.47 [1.08, 2.02]) and found the estimated CRP Scores to be inversely associated with risk of NSCLC risk after additionally adjusting for methylation-predicted pack-years (n = 150 pairs; Score 1 OR: 0.57 [0.40, 0.81]; Score 2 OR: 0.62 [0.45, 0.84]; Score 3 OR: 0.65 [0.44, 0.95]). Using Cox proportional-hazards models and adjusting age, sex, smoking status, methylation-predicted pack-years, BMI, batch effect, and stage, we observed a 27% increased risk of dying from lung cancer for one standard deviation increase in mdNLR (n = 145 deaths in 205 cases; HR: 1.27 [1.08, 1.50]). A 50% increased risk of dying from lung cancer for one standard deviation increase in mdNLR was observed for NSCLC cases (n = 103 deaths in 149 cases; HR: 1.50 [1.19, 1.89]).ConclusionsA better understanding of inflammation-associated methylation-based biomarkers in lung cancer development could provide insight into critical pathways that may help identify new markers of early disease and survival.

To demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem’s higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same “guild” if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of “guild” to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases. Supplementary Information The online version contains supplementary material available at 10.1186/s13073-021-00840-y.

Background: Oral microbiota is believed to play important roles in systemic diseases, including cancer. Methods: We collected oral samples (tongue, buccal, supragingival, and saliva) and pancreatic tissue or intestinal samples from 52 subjects, and characterized 16S rRNA genes using high-throughput DNA sequencing. Results: Bray–Curtis plot showed clear separations between bacterial communities in the oral cavity and those in intestinal and pancreatic tissue samples. PERMANOVA tests indicated that bacterial communities from buccal samples were similar to supragingival and saliva samples, and pancreatic duct samples were similar to pancreatic tumor samples, but all other samples were significantly different from each other. A total of 73 unique Amplicon Sequence Variants (ASVs) were shared between oral and pancreatic or intestinal samples. Only four ASVs showed significant concordance, and two specific bacterial species (Gemella morbillorum and Fusobacterium nucleatum subsp. vincentii) showed consistent presence or absence patterns between oral and intestinal or pancreatic samples, after adjusting for within-subject correlation and disease status. Lastly, microbial co-abundance analyses showed distinct strain-level cluster patterns among microbiome members in buccal, saliva, duodenum, jejunum, and pancreatic tumor samples. Conclusions: Our findings indicate that oral, intestinal, and pancreatic bacterial microbiomes overlap but exhibit distinct co-abundance patterns in patients with pancreatic cancer and other gastrointestinal diseases.

Additional file 1: Supplementary Table 1. The abundance of individual Eubacterium eligens strains, and that of the species and guilds presented in Fig. 3. The data were reported as Mean (S.E.M).

Knowledge Translation (KT) is the exchange, synthesis, and ethically-sound application of knowledge. A case study methodology is used to examine KT at the organizational level of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program.The study used purposeful sampling to select WIC informants from state WIC agencies to participate in semi-structured interviews about their individual experiences during the 2009 WIC regulation change process. Thematic coding of retrospective semi-structured interviews with key informants from WIC state agencies revealed key components of the state-level WIC regulation implementation process, and key constructs of Organizational Readiness for Knowledge Translation in the WIC program.WIC informants highlight that decisions made by WIC state agencies regarding how to appraise, synthesize, and adapt evidence or regulation change are constrained by the KT decisions made by federal agencies. WIC state agencies should assess their level of readiness for KT in terms of 1) innovation readiness; 2) personal readiness; and 3) institutional readiness.This WIC case study can help decision-makers to understand the KT process of implementing evidence-informed regulation changes, identify factors that could influence states' ability to be prepared for implementing changes, and gauge "practicality" of future WIC regulation changes.

Oral microbiota are believed to play important roles in systemic diseases, including cancer. We collected oral swabs and at least one pancreatic tissue or intestinal samples from 52 subjects, and characterized 16S ribosomal RNA genes using high-throughput DNA sequencing in a total 324 samples. We identified a total of 73 unique Amplicon Sequence Variants (ASVs) that were shared between oral and pancreatic or intestinal samples. Accounting for pairing and within-subject correlation, 7 ASVs showed significant concordance (Kappa statistics) and 5 ASVs exhibited significant or marginally significant Pairwise Stratified Association (PASTA) between oral samples and pancreatic tissue or intestinal samples. Of these, two specific bacterial species (Gemella morbillorum and Fusobacterium nucleatum subsp. vincentii) showed consistent presence or absence patterns between oral and intestinal or pancreatic samples. Lastly, our microbial co-abundance analyses showed several distinct ASVs clusters and complex correlation-networks between ASV clusters in buccal, saliva, duodenum, jejunum, and pancreatic tumor samples. Toghether, our findings suggest that oral, intestinal, and pancreatic microbiomes are correlated and bacteria of oral origin exhibit co-abundance relationships and demonstrate complex correlation patterns in the intestinal and pancreatic tumor samples. Future prospective studies should aim to uncover the co-abundance of specific microbial communities for studying etiology of microbiota-driven carcinogenesis.

There is increasing evidence that both black and green tea are beneficial for prevention of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis evaluating the effects of tea flavonoids on cardiovascular (CVD) and all-cause mortality outcomes.Searches across five databases including PubMed and Embase were conducted through November 2018 to identify randomized controlled trials (RCTs) and prospective cohort studies reporting cardiovascular and all-cause mortality outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments using the Nutrition Evidence Library Bias Assessment Tool (NEL BAT). Mixed-effects dose-response meta-regression and standard random-effects meta-analyses for outcomes with ≥ 4 studies were performed. 0 RCTs and 38 prospective cohort studies were included in the systematic review. NEL BAT scores ranged from 0–15 (0 being the lowest risk). Our linear meta-regression model showed that each cup increase in daily tea consumption (about 280 mg and 338 mg of total flavonoids for black and green tea, respectively) was associated with 3–4% lower risk of CVD mortality (predicted adjusted RR = 0.96; CI 0.93–0.99 for green tea and RR = 0.97; CI 0.94–0.99 for black tea). Furthermore, eachcup increase in daily tea consumption was associated a 2% lower risk of all-cause mortality (predicted adjusted relative risk (RR) = 0.98; 95% CI 0.97–0.99 for black tea and RR = 0.98; CI 0.96–0.99 for green tea, respectively). Two studies reported multivariable Cox regression analysis results for the relationship between black tea intake and risks of all-cause mortality outcomes. The results from these two studies were combined with our linear meta-regression result in a random-effects model meta-analysis and showed that each cup increase in daily black tea consumption was associated with an average of 3% lower risk of all-cause mortality (pooled adjusted RR = 0.97; 95% CI 0.87- 1.00) with large heterogeneity (I2 = 81.4%; p = 0.005). Current evidence indicates that increased tea consumption may reduce cardiovascular and all-cause mortality in a dose-response manner. This systematic review was registered on PROSPERO.

In 2020, studies have used pure cultures of members of the gut microbiota to establish a molecular chain of causation for the role of these key bacteria in aggravating or alleviating cancer and metabolic diseases. These studies highlight the need for microbiome studies to move from associations back to cultures to demonstrate causality.

The neutrophil-to-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and can be estimated using DNA methylation data as methylation-derived NLR (mdNLR). We examined associations between mdNLR and lung cancer risk in a nested case-control study, and among the cases, lung cancer survival, using pre-diagnostic blood samples of cases (median of 14 years before diagnosis) and controls in the CLUE I/II cohorts. The final analytic dataset included 208 pairs of lung cancer cases and controls matched on age, sex, and smoking intensity. We computed the mdNLR for each sample based on immune cell-proportion estimates obtained using established reference-based deconvolution methods. Using conditional logistic regression (to take into account matching factors), and further adjusting for BMI, batch effects, and a smoking-based methylation score, we observed a 47% increased risk of non-small cell lung cancer (NSCLC) for one standard deviation increase in mdNLR (n = 150 pairs; OR: 1.47 [1.08, 2.02]). To estimate association between mdNLR and lung cancer survival, we used Cox proportional-hazards models, adjusting age, sex, smoking status, smoking methylation score, BMI, batch effect, and stage. We observed a 27% increased risk of dying from lung cancer for one standard deviation increase in mdNLR (n = 145 deaths in 205 cases; HR: 1.27 [1.08, 1.50]). A 50% increased risk of dying from lung cancer for one standard deviation increase in mdNLR was observed for NSCLC cases (n = 103 deaths in 149 cases; HR: 1.50 [1.19, 1.89]). A better understanding of inflammation-associated biomarkers in lung cancer development could provide insight into critical pathways that may help identify new markers of early disease and survival. Citation Format: Naisi Zhao, Mengyuan Ruan, Devin Koestler, Jiayun Lu, Carmen Marsit, Karl Kelsey, Elizabeth Platz, Dominique S. Michaud. Methylation-derived neutrophil-to-lymphocyte ratio and lung cancer risk and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB086.

The mechanisms facilitating hypertension in diabetes still remain to be elucidated. Nonalcoholic fatty liver disease (NAFLD), which is a higher risk factor for insulin resistance, shares many predisposing factors with diabetes. However, little work has been performed on the pathogenesis of hypertension in type 2 diabetes (T2DM) with NAFLD. The aim of this study is to investigate the prevalence of hypertension in different glycemic statuses and to analyze relationships between NAFLD, metabolic risks, and hypertension within a large community-based population after informed written consent. A total of 9473 subjects aged over 45 years, including 1648 patients with T2DM, were enrolled in this cross-sectional study. Clinical and biochemical parameters of all participants were determined. The results suggested that the patients with prediabetes or T2DM were with higher risks to have hypertension. T2DM with NAFLD had significantly higher levels of blood pressure, triglyceride, uric acid, and HOMA-IR than those without NAFLD. Data analyses suggested that hypertriglyceridemia [OR = 1.773 (1.396, 2.251)], NAFLD [OR = 2.344 (1.736, 3.165)], hyperuricemia [OR = 1.474 (1.079, 2.012)], and insulin resistance [OR = 1.948 (1.540, 2.465)] were associated with the higher prevalence of hypertension independent of other metabolic risk factors in type 2 diabetes. Further studies are needed to focus on these associations.

Recent studies have found that the microbiome in both gut and mouth are associated with diseases of the gut, including cancer. If resident microbes could be found to exhibit consistent patterns between the mouth and gut, disease status could potentially be assessed non-invasively through profiling of oral samples. Currently, there exists no generally applicable method to test for such associations. Here we present a Bayesian framework to identify microbes that exhibit consistent patterns between body sites, with respect to a phenotypic variable. For a given operational taxonomic unit (OTU), a Bayesian regression model is used to obtain Markov-Chain Monte Carlo estimates of abundance among strata, calculate a correlation statistic, and conduct a formal test based on its posterior distribution. Extensive simulation studies demonstrate overall viability of the approach, and provide information on what factors affect its performance. Applying our method to a dataset containing oral and gut microbiome samples from 77 pancreatic cancer patients revealed several OTUs exhibiting consistent patterns between gut and mouth with respect to disease subtype. Our method is well powered for modest sample sizes and moderate strength of association and can be flexibly extended to other research settings using any currently established Bayesian analysis programs.

BACKGROUND/OBJECTIVES Due to the rapid increase of global cancer incidence and mortality and a high level of interest in cancer prevention, a systematic review of garlic intake and cancer risk is needed. SUBJECTS/METHODS We implemented a systematic review to examine the effects of varying levels of garlic intake on cancer. We conducted comprehensive literature searches in three electronic databases (MEDLINE, Embase, and Web of Science) for studies published between database inception and July or September of 2018. Two investigators independently screened abstracts and full-texts, extracted data, and assessed risk of bias (RoB). A total of one medium-quality randomized controlled trial (RCT) and 13 cohort studies graded as high RoB were included. RESULTS The 1-year follow-up results from a RCT showed that a significant decrease in the number and size of colorectal adenomas among participants with colorectal adenomas who received high-dose aged garlic extract (AGE) compared with those who received low-dose AGE (P < 0.05). The results of prospective observational studies provided inconsistent associations of colorectal cancer risk with garlic supplements and garlic intake as food. CONCLUSIONS In summary, the AGE was effective in reducing the number and magnitude of colorectal adenomas in one RCT, but there were inconsistent associations between garlic intake and colorectal cancer in cohort studies. Therefore, we could not draw a firm conclusion regarding the effects of garlic on cancer, because the current strength of evidence is inadequate due to a lack of number of high-quality RCTs.

Growing research has examined the association of oral microbiome with pancreatic cancer risk, but results have been inconsistent. Our previous study showed that bacterial taxa known to inhabit the oral cavity were common in the pancreas microbiome, and that bacterial DNA profiles in the pancreas were similar to those in the duodenum tissue of the same subjects regardless of disease state. These data suggest that bacteria may be migrating from oral into the gut and pancreas. We collected oral swabs and at least one pancreatic tissue or intestinal samples from subjects who underwent surgery for pancreatic diseases or diseases and characterized 16S ribosomal RNA genes using high-throughput DNA sequencing. We then quantified bacterial communities (Amplicon Sequence Variant level) at different body sites, investigated their co-abundance patterns, and analyzed the correlations between microbiome at oral sites and that in pancreatic tissue and intestinal samples using concordance statistics and Pairwise Stratified Association (PASTA) testing. The present analysis included 52 subjects (46% with pancreatic cancer; aged from 31 to 86 years old) contributing a total 324 samples. We identified a total of 73 unique Amplicon Sequence Variants (ASVs) that were shared between oral and pancreatic or intestinal samples. Accounting for pairing and within-subject correlation, 7 ASVs showed significant concordance (Kappa statistics) and 5 ASVs exhibited significant or marginally significant PASTA between oral samples and pancreatic tissue or intestinal samples. Of these, our PASTA analyses identified two specific bacterial species (Gemella morbillorum and Fusobacterium nucleatum subsp. vincentii) that showed consistent presence or absence patterns between oral and intestinal or pancreatic samples. Lastly, our microbial co-abundance analyses showed several distinct ASVs clusters and complex correlation-networks between ASV clusters in buccal, saliva, duodenum, jejunum, and pancreatic tumor samples. Oral, intestinal, and pancreatic microbiomes are correlated. Bacteria of oral origin exhibit co-abundance relationships and demonstrate complex correlation patterns in the intestinal and pancreatic tumor samples. Growing evidence has shown that bacterial species may survive, decline, and adapt as interdependent functional groups. Future studies should aim to uncover the co-abundance of specific microbial communities for studying etiology of microbiota-driven carcinogenesis in prospective and longitudinal studies. Citation Format: Mei Chung, Naisi Zhao, Richard Meier, Devein C. Koestler, Erika Del Castillo, Guojun Wu, Bruce J. Paster, Kevin Charpentier, Jacques Izard, Karl T. Kelsey, Dominique S. Michaud. Oral, intestinal, and pancreatic microbiomes are correlated and exhibit co-abundance in patients with pancreatic cancer and other gastrointestinal diseases [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B07.

The study is aimed to investigate the pathogenesis underlying the increased prevalence of thyroid nodule (TN) in different levels of metabolic syndrome (MetS) components and analyze the relationships between TN and MetS components. A total of 6,798 subjects, including 2201 patients with TN, were enrolled in this study. Anthropometric, biochemical, thyroid ultrasonographic, and other metabolic parameters were all measured. There was obviously sexual difference in the prevalence of TN (males 26.0%, females 38.5%, resp.). The prevalence of TN in hyperuricemia (45.7% versus 37.4%, P = 0.001), NAFLD (41.2% versus 36.4%, P < 0.05), and MetS (41.4% versus 35.4%, P < 0.001) groups was significantly increased only in females. Insulin resistance [OR = 1.31 (1.15, 1.49)], MetS [OR = 1.18 (1.03, 1.35)], and diabetes [OR = 1.25 (1.06, 1.48)] were all independent risk factors for TN in total subjects, whereas, after stratified analysis of gender, MetS [OR = 1.29, (1.09, 1.53)] and diabetes [OR = 1.47, (1.17, 1.84)] are still strongly and independently associated with the higher risks of TN in female subjects, but not in males. Our results suggest that the components of MetS might associate with the higher risks of TN in women than in men, but further cohort study of this gender disparity in the association between TN and MetS is required.

As a new hormone, betatrophin has gained attention as a potential new target to combat insulin resistance (IR) and diabetes. Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among women of the reproductive age with long term sequelae which include IR and metabolic syndrome. The aim of this study is to evaluate the circulating plasma betatrophin levels in overweight/obese or lean women with or without PCOS and also to elucidate possible correlations with anthropometric and metabolic parameters. Thirty-two patients with PCOS as well as fifty-three control subjects were enrolled after obtaining informed written consent. Clinical and biochemical parameters of all subjects were determined. Plasma adiponectin, GLP-1 and betatrophin levels were measured by ELISA. Plasma betatrophin levels were significantly increased in lean patients with PCOS compared with lean and obese controls. Moreover, in PCOS group, betatrophin levels were significantly negatively correlated with waist hip ratio (WHR), fasting insulin level (FINS) and HOMA-IR, whereas, significantly positively correlated with adiponectin level. Multiple regression analysis showed that HOMA-IR was an independent factor influencing serum betatrophin levels. Further follow-up studies are needed to highlight whether and how increased betatrophin secretion play an important role in IR and carbohydrates metabolism in patients with PCOS.

OBJECTIVES: To conduct a systematic review and meta-analysis evaluating the effects of tea flavonoids on cardiovascular (CVD) and all-cause mortality outcomes. METHODS: Searches across five databases including PubMed and Embase were conducted through November 2018 to identify randomized controlled trials (RCTs) and prospective cohort studies reporting cardiovascular and all-cause mortality outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments using the Nutrition Evidence Library Bias Assessment Tool (NEL BAT). Mixed-effects dose-response meta-regression and standard random-effects meta-analyses for outcomes with ≥4 studies were performed. RESULTS: 0 RCTs and 38 prospective cohort studies were included in the systematic review. NEL BAT scores ranged from 0–15 (0 being the lowest risk). Our linear meta-regression model showed that each cup increase in daily tea consumption (about 280 mg and 338 mg of total flavonoids for black and green tea, respectively) was associated with 3–4% lower risk of CVD mortality (predicted adjusted RR = 0.96; CI 0.93–0.99 for green tea and RR = 0.97; CI 0.94–0.99 for black tea). Furthermore, each cup increase in daily tea consumption was associated a 2% lower risk of all-cause mortality (predicted adjusted relative risk (RR) = 0.98; 95% CI 0.97–0.99 for black tea and RR = 0.98; CI 0.96–0.99 for green tea, respectively). Two studies reported multivariable Cox regression analysis results for the relationship between black tea intake and risks of all-cause mortality outcomes. The results from these two studies were combined with our linear meta-regression result in a random-effects model meta-analysis and showed that each cup increase in daily black tea consumption was associated with an average of 3% lower risk of all-cause mortality (pooled adjusted RR = 0.97; 95% CI 0.87–1.00) with large heterogeneity (I(2 )= 81.4%; p = 0.005). CONCLUSIONS: Current evidence indicates that increased tea consumption may reduce CVD and all-cause mortality in a dose-response manner. This systematic review was registered on PROSPERO. FUNDING SOURCES: Funding for this study was provided through an unrestricted educational grant from Unilever. The funding body had no influence on the study design; the collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the paper for publication.

OBJECTIVES: To understand the process of translating nutrition science for the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and to identify key organizational readiness constructs that will aid in future successful knowledge translation. METHODS: WIC food packages translate nutrition evidence into government program practices. In a public health decision-making setting, Knowledge Translation (KT) can be understood as action plans that promote evidence use and facilitate evidence-informed decision-making. A scoping review was conducted to conceptually map 38 available KT strategies with evidence-informed decisions made in public health settings. Next, building on this scoping review, a semi-structured interview guide was developed to analyze KT process and KT success at the state organizational level in the WIC program. Retrospective semi-structured interviews were conducted with 12 key informants from 7 WIC state agencies. RESULTS: Interviewees shared the steps they undertook in order to implement the 2009 WIC regulation changes, and discussed the roles WIC state agencies played in helping to align WIC food packages with the 2005 Dietary Guidelines for Americans. In addition, thematic coding revealed key constructs of Organizational Readiness for Knowledge Translation in the WIC program. A WIC state agency could assess its level of readiness for knowledge translation, and implementing evidence-informed regulation changes, in terms of: 1) innovation readiness; 2) personal readiness; and 3) institutional readiness. Innovation readiness refers to the fit between a WIC regulation change and existing WIC program processes and practices. Personal readiness encompasses WIC participant and stakeholder readiness, while institutional readiness incorporates organizational values and goals, organizational contextual factors, and organizational information channels. CONCLUSIONS: Decision-makers can use the constructs discovered in this study to understand the KT process of implementing evidence-informed WIC regulation changes, identify factors that could influence states’ ability to be prepared, and gauge “practicality” of future proposed federal rules. FUNDING SOURCES: Tufts University/University of Connecticut RIDGE Program Grant.

International audience; Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader-Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Ourmulti-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation. Research in context: Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found that children genetically obese with Prader-Willi syndrome shared a similar dysbiosis in their gut microbiota with those having diet-related obesity. A diet rich in non-digestible but fermentable carbohydrates significantly promoted beneficial groups of bacteria and reduced toxin-producers, which contributes to the alleviation of metabolic deteriorations in obesity regardless of the primary driving forces.

Chronic inflammation induced by endotoxin from a dysbiotic gut microbiota contributes to the development of obesity-related metabolic disorders. Modification of gut microbiota by a diet to balance its composition becomes a promising strategy to help manage obesity. A dietary scheme based on whole grains, traditional Chinese medicinal foods, and prebiotics (WTP diet) was designed to meet human nutritional needs as well as balance the gut microbiota. Ninety-three of 123 central obese volunteers (BMI ≥ 28 kg m(-2) ) completed a self-controlled clinical trial consisting of 9-week intervention on WTP diet followed by a 14-week maintenance period. The average weight loss reached 5.79 ± 4.64 kg (6.62 ± 4.94%), in addition to improvement in insulin sensitivity, lipid profiles, and blood pressure. Pyrosequencing of fecal samples showed that phylotypes related to endotoxin-producing opportunistic pathogens of Enterobacteriaceae and Desulfovibrionaceae were reduced significantly, while those related to gut barrier-protecting bacteria of Bifidobacteriaceae increased. Gut permeability, measured as lactulose/mannitol ratio, was decreased compared with the baseline. Plasma endotoxin load as lipopolysaccharide-binding protein was also significantly reduced, with concomitant decrease in tumor necrosis factor-α, interleukin-6, and an increase in adiponectin. These results suggest that modulation of the gut microbiota via dietary intervention may enhance the intestinal barrier integrity, reduce circulating antigen load, and ultimately ameliorate the inflammation and metabolic phenotypes.