Association Between Immune Response to Cytomegalovirus and Cognition in the Health and Retirement Study.

Chronic infections and the subsequent immune response have recently been shown to be risk factors for cognitive decline and Alzheimer disease and related dementias (ADRD). While some studies have shown an association between cytomegalovirus (CMV), a chronic and highly prevalent infection, and cognition and/or ADRD, these studies have been limited by nonrepresentative and small samples. Using 2016 data on 5,617 adults aged 65 years or more from the Health and Retirement Study, we investigated the cross-sectional associations of both CMV serostatus and immunoglobulin G (IgG) antibody response with cognitive function using linear regression models adjusting for age, sex, race/ethnicity, and educational attainment. We further investigated potential effect-measure modification by educational attainment. Overall, both CMV seropositivity and higher IgG antibody response were associated with lower cognitive function, though the relationship was not statistically significant in adjusted models. Among participants with less than a high school diploma, CMV seropositivity and being in the first tertile of IgG response, relative to seronegative persons, were associated with lower scores on the Telephone Interview for Cognitive Status (-0.56 points (95% confidence interval: -1.63, 0.52) and -0.89 points (95% confidence interval: -2.07, 0.29), respectively), and the relationship was attenuated among those with higher education. Our results suggest that CMV may be a risk factor for cognitive impairment, particularly among persons with fewer educational resources.

Sick Individuals and Sick (Microbial) Populations: Challenges in Epidemiology and the Microbiome.

The human microbiome represents a new frontier in understanding the biology of human health. While epidemiology in this area is still in its infancy, its scope will likely expand dramatically over the coming years. To rise to the challenge, we argue that epidemiology should capitalize on its population perspective as a critical complement to molecular microbiome research, allowing for the illumination of contextual mechanisms that may vary more across populations rather than among individuals. We first briefly review current research on social context and the gut microbiome, focusing specifically on socioeconomic status (SES) and race/ethnicity. Next, we reflect on the current state of microbiome epidemiology through the lens of one specific area, the association of the gut microbiome and metabolic disorders. We identify key methodological shortcomings of current epidemiological research in this area, including extensive selection bias, the use of noncompositionally robust measures, and a lack of attention to social factors as confounders or effect modifiers.

Pathogen burden and leukocyte telomere length in the United States.

BACKGROUND: Prior studies in humans have suggested that telomere shortening may be accelerated by infection, but research on multiple pathogens and use of large population-based study samples has been limited. We estimated cross-sectional associations between seropositivity to five persistent pathogens (Herpes Simplex Virus Type-1 (HSV-1), Herpes Simplex Virus Type-2 (HSV-2), cytomegalovirus (CMV), Helicobacter pylori (H.pylori), and Hepatitis B) as well as total pathogen burden and leukocyte telomere length. Data were derived from the National Health and Nutrition Examination Survey (1999-2000) for individuals 20-49 years of age, N = 1708. We analyzed the influence of each pathogen separately, a pathogen count score and a latent class model of pathogen burden on log telomere length using linear regression models, adjusted for covariates. RESULTS: Individuals in a latent pathogen burden class characterized by high probabilities of infection with HSV-1, CMV, and H. pylori, had significantly decreased log telomere length (- 0.30 [95% CI: - 0.36, - 0.24]) compared to those in a latent class characterized by low probabilities of all five infections. There were limited significant associations using other pathogen measures. CONCLUSIONS: These results suggest that infection with specific combinations of pathogens may be one mechanism contributing to accelerated cellular senescence with possible origins early in the life course.

HMP16SData: Efficient Access to the Human Microbiome Project Through Bioconductor.

Phase 1 of the Human Microbiome Project (HMP) investigated 18 body subsites of 242 healthy American adults to produce the first comprehensive reference for the composition and variation of the "healthy" human microbiome. Publicly available data sets from amplicon sequencing of two 16S ribosomal RNA variable regions, with extensive controlled-access participant data, provide a reference for ongoing microbiome studies. However, utilization of these data sets can be hindered by the complex bioinformatic steps required to access, import, decrypt, and merge the various components in formats suitable for ecological and statistical analysis. The HMP16SData package provides count data for both 16S ribosomal RNA variable regions, integrated with phylogeny, taxonomy, public participant data, and controlled participant data for authorized researchers, using standard integrative Bioconductor data objects. By removing bioinformatic hurdles of data access and management, HMP16SData enables epidemiologists with only basic R skills to quickly analyze HMP data.

The Mental Health Benefits of Acquiring a Home in Older Age: A Fixed-Effects Analysis of Older US Adults.

Homeownership is consistently associated with better mental health, but whether becoming a homeowner in later in life has positive psychological benefits has not, to our knowledge, been examined. We assessed whether acquiring a home after age 50 years was associated with depression in a representative sample of older US adults. We used individual fixed-effects models based on data from 20,524 respondents aged ≥50 years from the Health and Retirement Study, who were interviewed biennially during 1993-2010. Depressive symptoms were measured using the 8-item Center for Epidemiologic Studies Depression Scale. Controlling for confounders, becoming a homeowner in later life predicted a decline in depressive symptoms in the same year (ß = -0.0768, 95% confidence interval (CI): -0.152, -0.007). The association remained significant after 2 years (ß = -0.0556, 95% CI: -0.134, -0.001) but weakened afterward. Buying a home for reasons associated with positive characteristics of the new house or neighborhood drove this association (ß = -0.426, 95% CI: -0.786, -0.066), while acquiring a home for reasons associated with characteristics of the previous home or neighborhood, the desire to be closer to relatives, downsizing, or upsizing did not predict mental health improvements. Findings suggest that there are small but significant benefits for mental health associated with acquiring a home in older age.

Differences in the association between persistent pathogens and mood disorders among young- to middle-aged women and men in the U.S.

BACKGROUND: A growing literature supports the role of immune system alterations in the etiology of mood regulation, yet there is little population-based evidence regarding the association between persistent pathogens, inflammation and mood disorders among younger women and men in the U.S. METHODS: We used data from the National Health and Nutrition Examination Survey III on individuals 15-39 years of age assessed for major depression, dysthymia, and/or bipolar disorder I and tested for cytomegalovirus (N=6825), herpes simplex virus (HSV)-1 (N=5618) and/or Helicobacter pylori (H. pylori) (N=3167) seropositivity as well as C-reactive protein (CRP) level (N=6788). CMV immunoglobulin G (IgG) antibody level was also available for a subset of women (N=3358). We utilized logistic regression to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between pathogens, CRP levels and each mood disorder overall and among women and men, separately. RESULTS: H. pylori seropositivity was associated with increased odds of dysthymia (OR 2.37, 95% confidence interval (CI): 1.07, 5.24) among women, but decreased odds among men (OR 0.51, 95% CI: 0.28, 0.92). CMV seropositivity was also associated with lower odds of depression (OR 0.54, 95% CI: 0.32, 0.91) among men, while elevated CMV IgG level was marginally associated with increased odds of mood disorders among women. Associations were not mediated by CRP level. CONCLUSIONS: Our findings suggest that persistent pathogens such as CMV and H. pylori may differentially influence mood disorders among women and men, warranting further investigation into biological and/or sociocultural explanations for the contrasting associations observed.

Persistent Herpesvirus Infections and Telomere Attrition Over 3 Years in the Whitehall II Cohort.

The determinants of telomere attrition, a potential marker of cellular aging, are not well understood. Persistent herpesvirus infections including cytomegalovirus (CMV) infection may be particularly important for telomere dynamics via mechanisms such as inflammation, oxidative stress, and their impact on peripheral blood lymphocyte composition. This study examined the association of 4 human herpesviruses (CMV, herpes simplex virus type 1, human herpesvirus type 6, and Epstein-Barr virus) with change in leukocyte telomere length (LTL) over 3 years in 400 healthy individuals (aged 53-76 years) from the Whitehall II cohort. CMV, herpes simplex virus type 1, and human herpesvirus 6 infection were independently associated with greater 3-year LTL attrition, with no association found for Epstein-Barr virus. The magnitudes of these associations were large, for example, the equivalent of almost 12 years of chronological age for those CMV seropositive. Seropositivity to more herpesviruses was additively associated with greater LTL attrition (3 herpesviruses vs none, ß = -0.07 and P = .02; 4 infections vs none, ß = -0.14 and P < .001). Higher immunoglobulin G antibody levels among those seropositive to CMV were also associated with shorter LTL at follow-up. These associations were robust to adjustment for age, sex, employment grade, body mass index, and smoking status. These results suggest that exposure to infectious agents should be an important consideration in future studies of telomere dynamics.

Income and Markers of Immunological Cellular Aging.

OBJECTIVE: Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naïve cells (E/N ratio) and the CD4/CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E/N ratios and lower CD4/CD8 ratios compared with participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T cells. METHODS: Data were from 79 individuals who participated in the population-based Detroit Neighborhood Health Study. We used linear regression to quantify the association between a $10,000 decrease in income and each ratio outcome. RESULTS: After adjustment for age, sex, race, smoking, medication use, and lifetime history of mental health conditions, lower income was associated with a 0.41 (95% confidence interval = 0.09-0.72) log-unit increase in the CD4 E/N ratio and a 0.20 (95% confidence interval = 0.02-0.39) log-unit increase in the CD8 E/N ratio. CMV immunoglobulin G antibody level partially mediated these associations. CONCLUSIONS: Our study suggests that low socioeconomic status is associated with immunological aging as measured by the E/N ratio and that impaired immune control of CMV may partially mediate these associations.

Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.

AIMS/HYPOTHESIS: Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27(-)CD45RA(+/-); or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV(+) and CMV(-) individuals. METHODS: A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA(1c) and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27(-)CD45RA(-)) and CD45RA re-expressing effector memory (EMRA; CD27(-)CD45RA(+)) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors. RESULTS: Among CMV(+) individuals (n = 400), elevated HbA(1c) was associated with increased numbers of EM (B = 2.75, p < 0.01) and EMRA (B = 2.90, p < 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p < 0.05) after applying similar adjustments. No associations were observed in CMV(-) individuals. CONCLUSIONS/INTERPRETATION: The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV(+) individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence.

Employment and income losses among cancer survivors: Estimates from a national longitudinal survey of American families.

BACKGROUND: Cancer presents a substantial hardship for patients and their families in multiple domains beyond health and survival. Relatively little is known about the economic impact of cancer. The authors present estimates of the aggregate effects of a cancer diagnosis on employment and income in a prospective, nationally representative sample of US adults. METHODS: The authors used data from the 1990 through 2009 waves of the Panel Study of Income Dynamics, a nationally representative, prospective, population-based observational study with high-quality individual and family-level economic information. Age-adjusted, sex-stratified, individual fixed-effects regression models were used to derive estimates of the impact of cancer on employment, hours worked, individual income, and total family income. RESULTS: Significant effects of cancer on all 4 outcomes were observed. The probability of a cancer patient being employed dropped by almost 10 percentage points, and hours worked declined by up to 200 hours in the first year after diagnosis. Annual labor-market earnings dropped almost 40% within 2 years after diagnosis and remained low, whereas total family income declined by 20%, although it recovered within 4 years after the diagnosis. These economic impacts on survivors were driven by effects among men; the effects among women largely were not statistically significant. CONCLUSIONS: A cancer diagnosis has substantial effects on the economic well-being of affected adults and their families. With the increasing number of cancer survivors in the US population, there is a growing need for examining the long-term implications for economic well-being and ways to mitigate the economic hardship associated with cancer.

Pharmacologic androgen deprivation and cardiovascular disease risk factors: a systematic review.

BACKGROUND: Pharmacologic androgen deprivation therapy (ADT) is widely used to treat prostate cancer. Observational studies suggest ADT is associated with cardiovascular disease and its risk factors; however, such studies may be subject to bias. Our objective was to evaluate the effect of ADT on cardiovascular disease risk factors using data from randomized controlled trials (RCTs). MATERIALS AND METHODS: We conducted a systematic review using MEDLINE and MEDLINE In-Process (1950-June 2013), EMBASE (1974-June 2013) and Web of Science (1900-June 2013) for all RCTs in men with prostate cancer that compared pharmacologic ADT (i.e. use of gonadotropin-releasing hormone agonist or antagonist) with a group that did not receive ADT and reported data on cardiovascular disease risk factors including blood pressure, cholesterol, triglycerides, fibrinogen, biomarkers of insulin sensitivity, adiposity and C-reactive protein. We also searched for ongoing or unpublished trials. This study was registered at the PROSPERO International Prospective Register of Systematic Reviews (CRD42013005035). RESULTS: Of the 3272 unique publications identified in our systematic review, we did not identify a single RCT that reported data on any cardiovascular disease risk factor. We were unable to locate unreported data from corresponding authors or study sponsors. CONCLUSIONS: There is a lack of published, reliable evidence describing the effects of ADT on cardiovascular disease risk factors. RCTs have likely collected data on these risk factors as part of routine study monitoring; however, these data have not been published. To understand the effect of ADT on cardiovascular morbidity, these data must be made available to the scientific community.

Persistent viral pathogens and cognitive impairment across the life course in the third national health and nutrition examination survey.

BACKGROUND: Herpesviruses have been linked to cognitive impairment in older individuals but little is known about the association in the general US population. METHODS: We determined whether cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1) seropositivity were associated with cognitive impairment among children (aged 6-16 years) and adults aged 20-59 or ≥60 years, using data from the National Health and Nutrition Examination Survey (NHANES) III. Linear and logistic regression models were used to examine the associations between pathogen seropositivity and cognitive impairment. RESULTS: Among children, HSV-1 seropositivity was associated with lower reading and spatial reasoning test scores (ß, -0.69; 95% confidence interval [CI], -1.18 to -.21 and ß, -0.82; 95% CI, -1.29 to -.36, respectively). Among middle-aged adults, HSV-1 and CMV seropositivity were associated with impaired coding speed (odds ratio [OR], 1.54; 95% CI, 1.13-2.11, and OR, 1.41; 95% CI, 1.09-1.82, respectively). CMV seropositivity was also associated with impaired learning and recall (OR, 1.43; 95% CI, 1.14-1.80). Among older adults, HSV-1 seropositivity was associated with immediate memory impairment (OR, 3.26; 95% CI, 1.68-6.32). CONCLUSIONS: Future studies examining the biological pathways by which herpesviruses influence cognitive impairment across the life course are warranted.

Consistent associations between measures of psychological stress and CMV antibody levels in a large occupational sample.

Cytomegalovirus (CMV) is a herpes virus that has been implicated in biological aging and impaired health. Evidence, largely accrued from small-scale studies involving select populations, suggests that stress may promote non-clinical reactivation of this virus. However, absent is evidence from larger studies, which allow better statistical adjustment for confounding and mediating factors, in more representative samples. The present study involved a large occupational cohort (N=887, mean age=44, 88% male). Questionnaires assessed psychological (i.e., depression, anxiety, vital exhaustion, SF-12 mental health), demographic, socioeconomic (SES), and lifestyle variables. Plasma samples were analyzed for both the presence and level of CMV-specific IgG antibodies (CMV-IgG), used as markers for infection status and viral reactivation, respectively. Also assessed were potential biological mediators of stress-induced reactivation, such as inflammation (C-reactive protein) and HPA function (awakening and diurnal cortisol). Predictors of CMV infection and CMV-IgG among the infected individuals were analyzed using logistic and linear regression analyses, respectively. Confirming prior reports, lower SES (education and job status) was positively associated with infection status. Among those infected (N=329), higher CMV-IgG were associated with increased anxiety (ß=.14, p<.05), depression (ß=.11, p=.06), vital exhaustion (ß=.14, p<.05), and decreased SF-12 mental health (ß=-.14, p<.05), adjusting for a range of potential confounders. Exploratory analyses showed that these associations were generally stronger in low SES individuals. We found no evidence that elevated inflammation or HPA-function mediated any of the associations. In the largest study to date, we established associations between CMV-IgG levels and multiple indicators of psychological stress. These results demonstrate the robustness of prior findings, and extend these to a general working population. We propose that stress-induced CMV replication warrants further research as a psychobiological mechanism linking stress, aging and health.

Cohort differences in physical health and disability in the United States and Europe.

OBJECTIVES: Declines in mortality have historically been associated with improvements in physical health across generations. While life expectancy in most high-income countries continues to increase, there is evidence that younger generations, particularly in the United States (US), are less healthy than previous generations at the same age. We compared generational trends in physical health in the US, England, and continental Europe to explore whether other regions have experienced a similar pattern of worsening health across cohorts. METHODS: Using data from nationally representative studies of adults aged ≥50 years from the US (Health and Retirement Study, n=26,939), England (English Longitudinal Study of Ageing, n=14,992) and 11 continental European countries (Survey of Health, Ageing and Retirement in Europe, n=72,595), we estimated differences in the age-adjusted prevalence of self-reported chronic disease and disability and observer-measured health indicators across pseudo-birth cohorts (born <1925, 1925-1935, 1936-1945, 1946-1954, 1955-1959). RESULTS: Age-adjusted prevalence of doctor-diagnosed chronic disease increased across successive cohorts in all regions. Trends in disability prevalence were more regionally varied. Still, in both the US and Europe, we observed a structural break in disability trends, with declines observed in pre-war cohorts slowing, stalling, or reversing for cohorts born since 1945. DISCUSSION: In all regions, we found evidence for worsening health across cohorts, particularly for those born since 1945. While more chronic disease in younger cohorts need not necessarily translate to worse quality of life or higher rates of functional limitation, there is some suggestion that worsening chronic disease morbidity may be spilling over into worsening disability.

Generational differences in physical health and disability in the United States and Europe.

Objectives: Declines in mortality have typically been associated with improvements in physical health across generations. While life expectancy in most high-income countries continues to increase, there is evidence that younger generations, particularly in the United States (US), are less healthy than previous generations at the same age. We compared generational trends in physical health in the US, England, and continental Europe to explore whether other regions have experienced a similar pattern of worsening health across cohorts. Methods: Using data from nationally representative studies of adults aged ≥50 years from the US (Health and Retirement Study, n=26,939), England (English Longitudinal Study of Ageing, n=14,992) and 11 continental European countries (Survey of Health, Ageing and Retirement in Europe, n=72,595), we estimated differences in the age-adjusted prevalence of self-reported chronic disease and disability and observer-measured health indicators across pseudo-birth cohorts (born <1925, 1925-1935, 1936-1945, 1946-1954, 1955-1959). Results: Age-adjusted prevalence of doctor-diagnosed chronic disease increased across cohorts in all regions. Trends in disability prevalence were more regionally varied. Still, in both the US and Europe, we observed a structural break in disability trends, with declines observed in pre-war cohorts slowing, stalling, or reversing for cohorts born since 1945. Discussion: In all regions, we found evidence for worsening health across cohorts, particularly for those born since 1945. While more chronic disease in younger cohorts need not necessarily translate to worse quality of life or higher rates of functional limitation, there is some suggestion that worsening chronic disease morbidity may be spilling over into worsening disability.

An undue emphasis on rural older adults in the Chief Medical Officer's annual report 2023?

The Chief Medical Officer's annual report 2023 presents an incomplete and skewed picture of the geography of older people in England. We show that there are higher absolute numbers of older people in urban areas in England and Wales, in contrast to key messages from the CMO report which suggest greater need in rural areas based on relative metrics. The absolute size of the urban-rural difference in the population of older people is projected to grow by 2043. Older adults in urban areas are much more likely to live in deprived areas than older adults in rural areas. The absolute number and prevalence of older adults in poorer health is also higher in urban areas, leading to greater healthcare needs. Policy-makers need to consider both absolute and relative demographic trends as well as making use of direct measures of health when planning how healthcare services for older adults are distributed geographically in England.

Biological expressions of early life trauma in the immune system of older adults.

BACKGROUND: Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. METHODS: Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. FINDINGS: Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (ß = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (ß = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. INTERPRETATION: Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course.

Midlife Health in Britain and the US: A comparison of Two Nationally Representative Cohorts.

Background: Older adults in the United States (US) have worse health and wider socioeconomic inequalities in health compared to Britain. Less is known about how health in the two countries compares in midlife, a time of emerging health decline, including inequalities in health. Methods: We compare measures of smoking status, alcohol consumption, obesity, self-rated health, cholesterol, blood pressure, and glycated haemoglobin using population-weighted modified Poisson regression in the 1970 British Cohort Study (BCS70) in Britain (N= 9,665) and the National Longitudinal Study of Adolescent to Adult Health (Add Health) in the US (N=12,297), when cohort members were aged 34-46 and 33-43, respectively. We test whether associations vary by early- and mid-life socioeconomic position. Findings: US adults had higher levels of obesity, high blood pressure and high cholesterol. Prevalence of poor self-rated health, heavy drinking, and smoking was worse in Britain. We found smaller socioeconomic inequalities in midlife health in Britain compared to the US. For some outcomes (e.g., smoking), the most socioeconomically advantaged group in the US was healthier than the equivalent group in Britain. For other outcomes (hypertension and cholesterol), the most advantaged US group fared equal to or worse than the most disadvantaged groups in Britain. Interpretation: US adults have worse cardiometabolic health than British counterparts, even in early midlife. The smaller socioeconomic inequalities and better overall health in Britain may reflect differences in access to health care, welfare systems, or other environmental risk factors. Funding: ESRC, UKRI, MRC, NIH, European Research Council, Leverhulme Trust.

BugSigDB captures patterns of differential abundance across a broad range of host-associated microbial signatures.

The literature of human and other host-associated microbiome studies is expanding rapidly, but systematic comparisons among published results of host-associated microbiome signatures of differential abundance remain difficult. We present BugSigDB, a community-editable database of manually curated microbial signatures from published differential abundance studies accompanied by information on study geography, health outcomes, host body site and experimental, epidemiological and statistical methods using controlled vocabulary. The initial release of the database contains >2,500 manually curated signatures from >600 published studies on three host species, enabling high-throughput analysis of signature similarity, taxon enrichment, co-occurrence and coexclusion and consensus signatures. These data allow assessment of microbiome differential abundance within and across experimental conditions, environments or body sites. Database-wide analysis reveals experimental conditions with the highest level of consistency in signatures reported by independent studies and identifies commonalities among disease-associated signatures, including frequent introgression of oral pathobionts into the gut.