Gut Microbiota and Blood Metabolites Related to Fiber Intake and Type 2 Diabetes.

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D). METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at visit 2), serum metabolome measured by untargeted metabolomics (624 metabolites; n=6198 at baseline), and associations between fiber-related gut bacteria and metabolites (n=804 at visit 2). We examined prospective associations of serum microbial-associated metabolites (n=3579 at baseline) with incident T2D over 6 years. RESULTS: We identified multiple bacterial genera, species, and related enzymes associated with fiber intake. Several bacteria (eg, Butyrivibrio, Faecalibacterium) and enzymes involved in fiber degradation (eg, xylanase EC3.2.1.156) were positively associated with fiber intake, inversely associated with prevalent T2D, and favorably associated with T2D-related metabolic traits. We identified 159 metabolites associated with fiber intake, 47 of which were associated with incident T2D. We identified 18 of these 47 metabolites associated with the identified fiber-related bacteria, including several microbial metabolites (eg, indolepropionate and 3-phenylpropionate) inversely associated with the risk of T2D. Both Butyrivibrio and Faecalibacterium were associated with these favorable metabolites. The associations of fiber-related bacteria, especially Faecalibacterium and Butyrivibrio, with T2D were attenuated after further adjustment for these microbial metabolites. CONCLUSIONS: Among United States Hispanics/Latinos, dietary fiber intake was associated with favorable profiles of gut microbiota and circulating metabolites for T2D. These findings advance our understanding of the role of gut microbiota and microbial metabolites in the relationship between diet and T2D.

Dietary Acculturation Is Associated With Altered Gut Microbiome, Circulating Metabolites, and Cardiovascular Disease Risk in US Hispanics and Latinos: Results From HCHS/SOL.

BACKGROUND: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults. METHODS: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US exposure. We evaluated associations of dietary acculturation with incident CVD across ≈7 years of follow-up (n=211/14 172 cases/total) and gut microbiota (n=2349; visit 2, 2014 to 2017). Serum metabolites associated with both dietary acculturation-related gut microbiota (n=694) and incident CVD (n=108/5256 cases/total) were used as proxy measures to assess the association of diet-related gut microbiome with incident CVD. RESULTS: We identified an empirical US-oriented dietary acculturation score that increased with US exposure. Higher dietary acculturation score was associated with higher risk of incident CVD (hazard ratio per SD, 1.33 [95% CI, 1.13-1.57]), adjusted for sociodemographic, lifestyle, and clinical factors. Sixty-nine microbial species (17 enriched from diverse species, 52 depleted mainly from fiber-utilizing Clostridia and Prevotella species) were associated with dietary acculturation, driven by lower intakes of whole grains, beans, and fruits and higher intakes of refined grains. Twenty-five metabolites, involved predominantly in fatty acid and glycerophospholipid metabolism (eg, branched-chain 14:0 dicarboxylic acid** and glycerophosphoethanolamine), were associated with both diet acculturation-related gut microbiota and incident CVD. Proxy association analysis based on these metabolites suggested a positive relationship between diet acculturation-related microbiome and risk of CVD (r=0.70, P<0.001). CONCLUSIONS: Among US Hispanic and Latino adults, greater dietary acculturation was associated with elevated CVD risk, possibly through alterations in gut microbiota and related metabolites. Diet and microbiota-targeted interventions may offer opportunities to mitigate CVD burdens of dietary acculturation.

Cumulative All-Cause Mortality in Diverse Hispanic/Latino Adults : A Prospective, Multicenter Cohort Study.

BACKGROUND: All-cause mortality among diverse Hispanic/Latino groups in the United States and factors underlying mortality differences have not been examined prospectively. OBJECTIVE: To describe cumulative all-cause mortality (and factors underlying differences) by Hispanic/Latino background, before and during the COVID-19 pandemic. DESIGN: Prospective, multicenter cohort study. SETTING: Hispanic Community Health Study/Study of Latinos. PARTICIPANTS: 15 568 adults aged 18 to 74 years at baseline (2008 to 2011) of Central American, Cuban, Dominican, Mexican, Puerto Rican, South American, and other backgrounds from the Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California. MEASUREMENTS: Sociodemographic, acculturation-related, lifestyle, and clinical factors were assessed at baseline, and vital status was ascertained through December 2021 (969 deaths; 173 444 person-years of follow-up). Marginally adjusted cumulative all-cause mortality risks (11-year before the pandemic and 2-year during the pandemic) were examined using progressively adjusted Cox regression. RESULTS: Before the pandemic, 11-year cumulative mortality risks adjusted for age and sex were higher in the Puerto Rican and Cuban groups (6.3% [95% CI, 5.2% to 7.6%] and 5.7% [CI, 5.0% to 6.6%], respectively) and lowest in the South American group (2.4% [CI, 1.7% to 3.5%]). Differences were attenuated with adjustment for lifestyle and clinical factors. During the pandemic, 2-year cumulative mortality risks adjusted for age and sex ranged from 1.1% (CI, 0.6% to 2.0%; South American) to 2.0% (CI, 1.4% to 3.0%; Central American); CIs overlapped across groups. With adjustment for lifestyle factors, 2-year cumulative mortality risks were highest in persons of Central American and Mexican backgrounds and lowest among those of Puerto Rican and Cuban backgrounds. LIMITATION: Lack of data on race and baseline citizenship status; correlation between Hispanic/Latino background and site. CONCLUSION: Differences in prepandemic mortality risks across Hispanic/Latino groups were explained by lifestyle and clinical factors. Mortality patterns changed during the pandemic, with higher risks in persons of Central American and Mexican backgrounds than in those of Puerto Rican and Cuban backgrounds. PRIMARY FUNDING SOURCE: National Institutes of Health.

Air quality and cancer risk in the All of Us Research Program.

INTRODUCTION: The NIH All of Us Research Program has enrolled over 544,000 participants across the US with unprecedented racial/ethnic diversity, offering opportunities to investigate myriad exposures and diseases. This paper aims to investigate the association between PM2.5 exposure and cancer risks. MATERIALS AND METHODS: This work was performed on data from 409,876 All of Us Research Program participants using the All of Us Researcher Workbench. Cancer case ascertainment was performed using data from electronic health records and the self-reported Personal Medical History questionnaire. PM2.5 exposure was retrieved from NASA's Earth Observing System Data and Information Center and assigned using participants' 3-digit zip code prefixes. Multivariate logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Generalized additive models (GAMs) were used to investigate non-linear relationships. RESULTS: A total of 33,387 participants and 46,176 prevalent cancer cases were ascertained from participant EHR data, while 20,297 cases were ascertained from self-reported survey data from 18,133 participants; 9,502 cancer cases were captured in both the EHR and survey data. Average PM2.5 level from 2007 to 2016 was 8.90 µg/m3 (min 2.56, max 15.05). In analysis of cancer cases from EHR, an increased odds for breast cancer (OR 1.17, 95% CI 1.09-1.25), endometrial cancer (OR 1.33, 95% CI 1.09-1.62) and ovarian cancer (OR 1.20, 95% CI 1.01-1.42) in the 4th quartile of exposure compared to the 1st. In GAM, higher PM2.5 concentration was associated with increased odds for blood cancer, bone cancer, brain cancer, breast cancer, colon and rectum cancer, endocrine system cancer, lung cancer, pancreatic cancer, prostate cancer, and thyroid cancer. CONCLUSIONS: We found evidence of an association of PM2.5 with breast, ovarian, and endometrial cancers. There is little to no prior evidence in the literature on the impact of PM2.5 on risk of these cancers, warranting further investigation.

Associations of Anxiety Symptoms With 6-Year Blood Pressure Changes and Incident Hypertension: Results From the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Despite the high burden of anxiety and hypertension in Hispanic/Latino adults, little is known about their association in this population. PURPOSE: To examine the associations of anxiety symptoms with 6-year changes in blood pressure (BP) and incident hypertension in Hispanic/Latino adults. METHODS: We examined data from a probability sample of 10,881 Hispanic/Latino persons aged 18-74 who attended visits 1 (V1; 2008-2011) and 2 (V2; 2014-2017) of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a prospective cohort study. Anxiety symptoms were assessed at V1 using the 10-item Spielberger Trait Anxiety Scale (M = 17.1; Range = 10-40) and dichotomized using a cut-point of 20, the highest quartile in this cohort. BP was measured at both visits using a standardized protocol. RESULTS: Adults with elevated anxiety symptoms had a 1.02 mm Hg greater increase in systolic (p = .02) and a 0.75 mm Hg greater increase in diastolic BP (p = .02) over 6.1 years than those with lower symptoms, after adjusting for sociodemographic and clinical covariates. These associations differed by sex. Elevated anxiety was associated with a greater increase in systolic and diastolic BP in men only. Among persons without hypertension at V1 (N = 7,412), those with elevated anxiety symptoms at V1 had a 22% higher incidence of hypertension (p = .02) 6.1 years later. CONCLUSIONS: Our findings underscore the importance of screening for and treating elevated anxiety symptoms to help prevent hypertension. Further research on the role of sex and underlying mechanisms is warranted.

This study investigated the relationship between anxiety symptoms and changes in blood pressure, as well as the incidence of hypertension among Hispanic/Latino adults over time. Using data from 10,881 Hispanic/Latino adults who participated in the Hispanic Community Health Study/Study of Latinos, we found that men, but not women, with elevated anxiety symptoms experienced a greater increase in both systolic and diastolic blood pressure over a 6-year period compared to those with lower symptoms. Additionally, among 7,412 participants who were free of hypertension at baseline, individuals with elevated anxiety symptoms developed hypertension at a higher rate after 6 years of follow-up compared to those with lower symptoms. These findings suggest that anxiety symptoms play a role in the development of hypertension among Hispanic/Latino adults, underscoring the importance of screening for and addressing elevated anxiety to potentially prevent hypertension.

Sleep duration and brain MRI measures: Results from the SOL-INCA MRI study.

INTRODUCTION: Sleep duration has been associated with dementia and stroke. Few studies have evaluated sleep pattern-related outcomes of brain disease in diverse Hispanics/Latinos. METHODS: The SOL-INCA (Study of Latinos-Investigation of Neurocognitive Aging) magnetic resonance imaging (MRI) study recruited diverse Hispanics/Latinos (35-85 years) who underwent neuroimaging. The main exposure was self-reported sleep duration. Our main outcomes were total and regional brain volumes. RESULTS: The final analytic sample included n = 2334 participants. Increased sleep was associated with smaller brain volume (ßtotal_brain  = -0.05, p < 0.01) and consistently so in the 50+ subpopulation even after adjusting for mild cognitive impairment status. Sleeping >9 hours was associated with smaller gray (ßcombined_gray  = -0.17, p < 0.05) and occipital matter volumes (ßoccipital_gray  = -0.18, p < 0.05). DISCUSSION: We found that longer sleep duration was associated with lower total brain and gray matter volume among diverse Hispanics/Latinos across sex and background. These results reinforce the importance of sleep on brain aging in this understudied population. HIGHLIGHTS: Longer sleep was linked to smaller total brain and gray matter volumes. Longer sleep duration was linked to larger white matter hyperintensities (WMHs) and smaller hippocampal volume in an obstructive sleep apnea (OSA) risk group. These associations were consistent across sex and Hispanic/Latino heritage groups.

Psychosocial factors associated with 7-year change in cognition among middle-aged and older Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) and Sociocultural ancillary studies.

INTRODUCTION: Few studies have examined the associations of psychosocial factors with cognitive change in Hispanics/Latinos. METHODS: Data from the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL INCA) and Sociocultural studies were used (n = 2,155; ages ≥45 years). Psychosocial exposures included intrapersonal (ethnic identity, optimism, purpose in life), interpersonal (family cohesion, familism, social networks, social support), and social factors (ethnic discrimination, loneliness, subjective social status). Survey-linear regression models examined associations between psychosocial exposures and 7-year cognitive change (global cognition [GC], verbal learning, memory, word fluency [WF], and digit symbol substitution [DSS]). RESULTS: Familism predicted decline in GC, verbal learning, and memory; family cohesion predicted DSS decline; and loneliness predicted memory decline. Ethnic identity was protective against decline in GC and memory, optimism and social support were protective against decline in memory, and purpose in life was protective against WF decline. DISCUSSION: Psychosocial factors are differentially related to cognitive changes. Culturally relevant factors should be explored in Hispanic/Latino cognitive aging research. HIGHLIGHTS: Psychosocial factors are differentially related to cognitive changes in Latinos. Role of culturally relevant factors on cognition should be further explored. Familism predicted decline in global cognition, verbal learning, and memory. Ethnic identity predicted increase in global cognition and memory.

Admixture mapping of cognitive function in diverse Hispanic and Latino adults: Results from the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: We conducted admixture mapping and fine-mapping analyses to identify ancestry-of-origin loci influencing cognitive abilities. METHODS: We estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts. RESULTS: We identified nine local ancestry-associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13. DISCUSSION: Our study identified multiple novel loci harboring genes implicated in cognitive functioning and dementia, and uncovered ancestry-relevant genetic variants. It adds to our understanding of the genetic architecture of cognitive function in Hispanic and Latino adults and demonstrates the power of admixture mapping to discover unique haplotypes influencing cognitive function, complementing genome-wide association studies. HIGHLIGHTS: We identified nine ancestry-of-origin chromosomal regions associated with five neurocognitive traits. In each associated region, we identified single nucleotide polymorphisms (SNPs) that explained, at least in part, the admixture signal and were tested for replication in independent samples of Black, non-Hispanic White, and Hispanic/Latino adults with the same or similar neurocognitive tests. Statistical evidence of independent replication of the prioritized SNPs was observed for three of the nine associations, at chr4q12, chr9p22.1, and chr13q12.13. At all loci, there was strong biological support for the observed associations to cognitive function and dementia, prioritizing genes such as KIT, implicated in autophagic clearance of neurotoxic proteins and on mast cell and microglial-mediated inflammation; SLC24A2, implicated in synaptic plasticity associated with learning and memory; and MTMR6, implicated in phosphoinositide lipids metabolism.

Nutritional Blood Concentration Biomarkers in the Hispanic Community Health Study/Study of Latinos: Measurement Characteristics and Power.

Measurement error is a major issue in self-reported diet that can distort diet-disease relationships. Use of blood concentration biomarkers has the potential to mitigate the subjective bias inherent in self-reporting. As part of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline visit (2008-2011), self-reported information on diet was collected from all participants (n = 16,415). The HCHS/SOL also included annual telephone follow-up, as well as a second (2014-2017) and third (2020-2023) clinic visit. Blood concentration biomarkers for carotenoids, tocopherols, retinol, vitamin B12, and folate were measured in a subset of participants (n = 476) as part of the Study of Latinos: Nutrition and Physical Activity Assessment Study (SOLNAS) (2010-2012). We examined the relationships among biomarker levels, self-reported intake, Hispanic/Latino background (Central American, Cuban, Dominican, Mexican, Puerto Rican, or South American), and other participant characteristics in this diverse cohort. We built regression calibration-based prediction equations for 10 nutritional biomarkers and used a simulation to study the power of detecting a diet-disease association in a multivariable Cox model using a predicted concentration level. Good statistical power was observed for some nutrients with high prediction model R2 values, but further research is needed to understand how best to realize the potential of these dietary biomarkers. This study provides a comprehensive examination of several nutritional biomarkers within the HCHS/SOL, characterizing their associations with subject characteristics and the influence of the measurement characteristics on the power to detect associations with health outcomes.

Childhood and Life-Course Socioeconomic Position and Cognitive Function in the Adult Population of the Hispanic Community Health Study/Study of Latinos.

The Hispanic/Latino population experiences socioeconomic adversities across the lifespan and is at greater risk of cognitive impairment, yet little is known about the role of life-course socioeconomic position (SEP) in cognitive function in this population. Using baseline data (2008-2011) from adults (aged 45-74 years) of the Hispanic Community Health Study/Study of Latinos, we assessed the association between childhood SEP and socioeconomic mobility with cognitive function, and whether this association was mediated by midlife SEP. Childhood SEP was assessed using parental education. An index combining participants' education and household income represented midlife SEP. Socioeconomic mobility was categorized as stable low, downward or upward mobility, and stable high-SEP. Cognitive function measures were modeled using survey linear regression with inverse-probability weighting, accounting for covariates. We used mediation analysis to estimate the indirect effect of childhood SEP on cognition through midlife SEP. High childhood SEP was associated with global cognition in adulthood (coefficient for parental education beyond high school vs. less than high school = 0.26, 95% confidence interval: 0.15, 0.37). This association was partially mediated through midlife SEP (indirect effect coefficient = 0.16, 95% confidence interval: 0.15, 0.18). Low SEP through the life course was associated with the lowest cognitive function. This study provides evidence that life-course SEP influences cognitive performance in adulthood.

Risk Factors for Cardiovascular Disease: Knowledge Gained from the Hispanic Community Health Study/Study of Latinos.

PURPOSE OF REVIEW: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) has made important contributions on the prevalence of and factors associated with cardiovascular disease (CVD) risk factors among diverse Hispanic/Latino adults in the US. This article summarizes the knowledge gained thus far on major CVD risk factors from this landmark study. RECENT FINDINGS: HCHS/SOL demonstrated the sizeable burdens of CVD risk in all major Hispanic/Latino groups in the US, as well as the marked variations in prevalence of hypertension, hypercholesterolemia, diabetes, obesity, and smoking by sex and background. It also identified sociodemographic, lifestyle, and sociocultural characteristics associated with risk factors. HCHS/SOL has yielded an expanding body of literature on characteristics associated with adverse CVD risk factors in this population. Long-term follow-up of this cohort will shed further light on the observed heterogeneity in CVD risk across Hispanic/Latino groups and identify specific risk/protective factors driving these variations.

Religion/Spirituality and Prevalent Hypertension among Ethnic Cohorts in the Study on Stress, Spirituality, and Health.

BACKGROUND: Hypertension is a significant public health issue, particularly for Blacks, Hispanics/Latinos, and South Asians who are at greater risk than whites. Religion and spirituality (R/S) have been shown to be protective, but this has been identified primarily in whites with limited R/S measures examined (i.e., religious service attendance). PURPOSE: To assess hypertension prevalence (HP) in four racial/ethnic groups while incorporating an array of R/S variables, including individual prayer, group prayer, nontheistic daily spiritual experiences, yoga, gratitude, positive religious coping, and negative religious coping. METHODS: Data were drawn from the Study on Stress, Spirituality, and Health, a consortium of ethnically diverse U.S. cohorts. The sample included 994 Black women, 838 Hispanic/Latino men and women, 879 South Asian men and women, and 3681 white women. Using a cross-sectional design, prevalence ratios for R/S and hypertension were reported for each cohort, in addition to pooled analyses. Given differences in R/S among men and women, all models were stratified by gender. RESULTS: Different patterns of associations were found between women and men. Among women: 1) religious attendance was associated with lower HP among Black and white women; 2) gratitude was linked to lower HP among Hispanic/Latino, South Asian, and white women; 3) individual prayer was associated with higher HP among Hispanic/Latino and white women; 4) yoga was associated with higher HP among South Asian women, and 5) negative religious coping was linked to higher HP among Black women. Among men: significant results were only found among Hispanic/Latino men. Religious attendance and individual prayer were associated with higher HP, while group prayer and negative religious coping were associated with lower HP. CONCLUSION: Religion/spirituality is a multifaceted construct that manifests differently by race/ethnicity and gender. Medical practitioners should avoid a one-size-fits-all approach to this topic when evaluating prevalent hypertension in diverse communities.

Hypertension is a serious public health issue that affects many Americans, though non-whites are at greater risk than whites. In this study, we examine Black, Hispanic/Latino, and South Asian samples, comparing their hypertension rates to whites. We ask whether one or more aspects of religion and spirituality (R/S) might be associated with prevalent hypertension (i.e., prevalence of hypertension at a single point in time). Religious service attendance is the primary R/S variable examined in relation to hypertension, but we expand this to include individual prayer, prayer in groups, daily spiritual experiences, yoga practice, feelings of gratitude, using God to help cope with problems (positive religious coping), and experiencing doubt or fear about God in the face of challenges (negative religious coping). The results were mixed across racial/ethnic group and gender. Among women, higher religious attendance and gratitude were associated with lower hypertension prevalence, but individual prayer was associated with higher prevalence. Few associations were noted between R/S and hypertension among men. Given these findings, along with extant research, it is important for medical practitioners serving diverse communities to recognize R/S may operate differently for men and women in varied religious and ethnic groups, with differing implications for prevalent hypertension.

Cultural and neighborhood characteristics associated with activity-specific parenting practices in Hispanic/Latino youth: a secondary analysis of the Hispanic Community Children's health study/study of Latino youth.

Hispanic/Latino youth are less physically active than non-Hispanic/Latino youth. We assessed whether activity-specific parenting practices relate to moderate-to-vigorous physical activity (MVPA) and sedentary behavior among Hispanic/Latino youth, and whether cultural (acculturation) and neighborhood characteristics (perceived barriers to activity) relate to the use of parenting practice patterns. Using the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth, n = 976 8-16-year-olds), we modeled linear regression associations between parenting practices and mean daily MVPA and sedentary behavior. Parenting practice patterns were then developed using k-means cluster analysis, and regressed on parental acculturation and neighborhood characteristics. Discipline predicted higher MVPA in females (ß 1.89 [95% CI 0.11-3.67]), while Monitoring/Reinforcement predicted higher MVPA in males (ß 4.71 [95% CI 0.68-8.74]). Three patterns were then identified: Negative Reinforcement (high Limit Setting and Discipline use), Positive Reinforcement (high Limit Setting and Monitoring/Reinforcement use), and Permissive Parenting (low parenting practice use). Higher acculturation predicted use of Positive Reinforcement. Activity-specific parenting practices are associated with activity in sex-specific ways among Hispanic/Latino youth, and cultural factors predict the use of parenting practices.

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

Genome-Wide Admixture Mapping of Estimated Glomerular Filtration Rate and Chronic Kidney Disease Identifies European and African Ancestry-of-Origin Loci in Hispanic and Latino Individuals in the United States.

BACKGROUND: Admixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture, such as Hispanic or Latino individuals in the United States. These individuals have an increased risk of CKD. METHODS: We performed genome-wide admixture mapping for both CKD and eGFR in a sample of 12,601 participants from the Hispanic Community Health Study/Study of Latinos, with validation in a sample of 8191 Black participants from the Women's Health Initiative (WHI). We also compared the findings with those from a conventional genome-wide association study. RESULTS: Three novel ancestry-of-origin loci were identified on chromosomes 2, 14, and 15 for CKD and eGFR. The chromosome 2 locus comprises two European ancestry regions encompassing the FSHR and NRXN1 genes, with European ancestry at this locus associated with increased CKD risk. The chromosome 14 locus, found within the DLK1-DIO3 imprinted domain, was associated with lower eGFR and driven by European ancestry. The eGFR-associated locus on chromosome 15 included intronic variants of RYR3 and was within an African-specific genomic region associated with higher eGFR. The genome-wide association study failed to identify significant associations in these regions. We validated the chromosome 14 and 15 loci associated with eGFR in the WHI Black participants. CONCLUSIONS: This study provides evidence of shared ancestry-specific genomic regions influencing eGFR in Hispanic or Latino individuals and Black individuals and illustrates the potential for leveraging genetic ancestry in recently admixed populations for the discovery of novel candidate loci for kidney phenotypes.

Host and gut microbial tryptophan metabolism and type 2 diabetes: an integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies.

OBJECTIVE: Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota. METHOD: We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites. RESULTS: Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals. CONCLUSION: Higher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host-microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.

Healthful eating patterns, serum metabolite profile and risk of diabetes in a population-based prospective study of US Hispanics/Latinos.

AIMS/HYPOTHESIS: We aimed to evaluate associations of multiple recommended dietary patterns (i.e. the alternate Mediterranean diet [aMED], the Healthy Eating Index [HEI]-2015 and the healthful Plant-based Diet Index [hPDI]) with serum metabolite profile, and to examine dietary-pattern-associated metabolites in relation to incident diabetes. METHODS: We included 2842 adult participants free from diabetes, CVD and cancer during baseline recruitment of the Hispanic Community Health Study/Study of Latinos. Metabolomics profiling of fasting serum was performed using an untargeted approach. Dietary pattern scores were derived using information collected by two 24 h dietary recalls. Dietary-pattern-associated metabolites were identified using multivariable survey linear regressions and their associations with incident diabetes were assessed using multivariable survey Poisson regressions with adjustment for traditional risk factors. RESULTS: We identified eight metabolites (mannose, γ/ß-tocopherol, N1-methylinosine, pyrraline and four amino acids) that were inversely associated with all dietary scores. These metabolites were detrimentally associated with various cardiometabolic risk traits, especially insulin resistance. A score comprised of these metabolites was associated with elevated risk of diabetes (RRper SD 1.54 [95% CI 1.29, 1.83]), and this detrimental association appeared to be attenuated or eliminated by having a higher score for aMED (pinteraction = 0.0001), HEI-2015 (pinteraction = 0.020) or hPDI (pinteraction = 0.023). For example, RR (95% CI) of diabetes for each SD increment in the metabolite score was 1.99 (1.44, 2.37), 1.67 (1.17, 2.38) and 1.08 (0.86, 1.34) across the lowest to the highest tertile of aMED score, respectively. CONCLUSIONS/INTERPRETATION: Various recommended dietary patterns were inversely related to a group of metabolites that were associated with elevated risk of diabetes. Adhering to a healthful eating pattern may attenuate or eliminate the detrimental association between metabolically unhealthy serum metabolites and risk of diabetes.

Metabolome-wide association study of estimated glomerular filtration rates in Hispanics.

Circulating metabolites are by-products of endogenous metabolism or exogenous sources and may inform disease states. Our study aimed to identify the source of variability in the association of metabolites with estimated glomerular filtration rate (eGFR) in Hispanics/Latinos with low chronic kidney disease prevalence by testing the association of 640 metabolites in 3,906 participants of the Hispanic Community Health Study/Study of Latinos. Metabolites were quantified in fasting serum through non-targeted mass spectrometry analysis. eGFR was regressed on inverse normally transformed metabolites in models accounting for study design and covariates. To identify the source of variation on eGFR associations, we tested the interaction of metabolites with lifestyle and clinical risk factors, and results were integrated with genotypes to identify metabolite genetic regulation. The mean age was 46 years, 43% were men, 22% were current smokers, 47% had a Caribbean Hispanic background, 19% had diabetes and the mean cohort eGFR was 96.4 ml/min/1.73 m2. We identified 404 eGFR-metabolite associations (False Discovery Rate under 0.05). Of these, 69 were previously reported, and 79 were novel associations with eGFR replicated in one or more published studies. There were significant interactions with lifestyle and clinical risk factors, with larger differences in eGFR-metabolite associations within strata of age, urine albumin to creatinine ratio, diabetes and Hispanic/Latino background. Several newly identified metabolites were genetically regulated, and variants were located at genomic regions previously associated with eGFR. Thus, our results suggest complex mechanisms contribute to the association of eGFR with metabolites and provide new insights into these associations.

Seroprevalence and Determinants of Helicobacter pylori Infection in the Hispanic Community Health Study/Study of Latinos.

BACKGROUND & AIMS: Helicobacter pylori infection is the primary known risk factor for gastric cancer. Despite the global decline in H. pylori prevalence, this infection remains a major public health concern in developing areas, including Latin America. Our study aimed to determine H. pylori seroprevalence and identified its determinants among Hispanics/Latinos living in the United States (U.S.). METHODS: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a population-based sample of self-identified Hispanics/Latinos (n = 16,144) in four U.S. communities, aged 18 to 74 years, recruited from randomly selected households using a stratified two-stage area probability sample design based on sampling households within sampled census block groups weighted for differential response rates. Anti-H. pylori immunoglobulin G antibodies were measured by an enzyme-linked immunosorbent assay using plasma samples. We calculated adjusted seroprevalence (i.e., predicted margins) from multivariable logistic regression models. RESULTS: The overall weighted H. pylori seroprevalence was 57% among HCHS/SOL participants, with 38% and 62% seropositivity among U.S.-born and non-U.S.-born individuals, respectively. Age-adjusted prevalence varied by self-reported Hispanic/Latino background, ranging from 47% in Puerto Rican to 72% in Central American backgrounds. Adjusted H. pylori seroprevalence was higher in the following groups: older age, male sex, lower education, non-U.S. born status, smoking, greater number of missing teeth, fewer doctor visits, lower ferritin level, and hepatitis A seropositivity. CONCLUSIONS: H. pylori seroprevalence in Hispanics/Latinos remains high and differed significantly by Hispanic/Latino background. H. pylori seropositivity is strongly associated with poor socioeconomic conditions. These findings highlight the ongoing importance of this bacterial infection in the U.S.

Perceived neighborhood factors, health behaviors, and related outcomes in the Hispanic Community Health Study/Study of Latinos.

Hispanic/Latino populations may experience significant neighborhood disadvantage, but limited research has explored whether these factors affect their health behaviors. Associations between perceived neighborhood factors at Visit 1 and health behaviors and related outcomes at Visit 2 in the Hispanic Community Health Study/Study of Latinos were evaluated. Multivariable logistic regression assessed cross-sectional and longitudinal relationships between perceived neighborhood social cohesion (NSC, 5 items), and neighborhood problems (NP, 7 items), with cancer screening, current smoking, excessive/binge drinking, hypertension, obesity, physical activity, and poor diet by gender and birthplace. NSC and NP scores were converted into quartiles. Mean age of participants was 42.5 years and 62.1% were women. Perceived NP, but not perceived NSC, differed by gender (p < 0.001). In unstratified models, no significant associations were observed between perceived NSC and any health behavior, whereas greater perceived NP was associated with less adherence to colon cancer screening (moderate level: aOR = 0.68, 95% CI = 0.51, 090) and more physical activity (very high level: aOR = 1.34, 95% CI = 1.06, 1.69) compared to low perceived NP. Women with moderate perceived NP, versus low NP, had a lower odds of colon cancer screening at Visit 1 (aOR = 0.62, 95% CI = 0.43, 0.91) and higher odds of mammogram adherence at Visit 2 (aOR = 2.86, 95% CI = 1.44, 5.68). Men with high perceived NP had a higher odds of excessive or binge drinking at Visit 2 (aOR = 1.99, 95% CI = 1.19, 3.31). We conclude that perceived NP were significantly related to health behaviors among HCHS/SOL individuals. Perceptions of neighborhood environment may be considered modifiable factors of structural neighborhood environment interventions.