Background: Alterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection. Methods: We analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up. Results: We found 2 potentially pathogenic bacteria, Fusobacterium and Proteus , were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09–1.64] and 1.24 [1.02–1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines. Conclusions: Among individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.

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-patternassociated 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/β-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 insulinresistance.Ascorecomprisedofthesemetaboliteswasassociatedwithelevatedriskofdiabetes(RR per SD 1.54[95%CI1.29,1.83]), and this detrimental association appeared to be attenuated or eliminated by having a higher score for aMED (p interaction = 0.0001), HEI-2015 (p interaction = 0.020) or hPDI (p interaction = 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.

Background Multiple dietary patterns haven been recommended by 2015–2020 Dietary Guidelines for Americans for the prevention of cardiovascular disease (CVD). The adherence to these patterns and its relationship with risk of CVD remain unclear in the US Hispanic/Latino population. Objectives We aimed to evaluate three healthy eating patterns measured by three dietary pattern scores (the Alternate Mediterranean diet (aMED), the Healthy Eating Index (HEI)-2015, and the healthful Plant-based Diet Index (hPDI)) across different Hispanic/Latino backgrounds and generations. We further examined the associations of these dietary scores with incident CVD in US Hispanics/Latinos. Methods We included 10,293 adult participants of US Hispanics/Latinos of six backgrounds (Mexican, Puerto Rican, Cuban, Dominican, Central American and South American), free of CVD or cancer at baseline, in the Hispanic Community Health Study/Study of Latinos. Dietary pattern scores were derived at the baseline visit using two 24-hour dietary recalls. The primary outcome was the major incident CVD (n = 232), comprised of coronary heart disease and stroke, during an average 6-year follow-up. Results Mean levels of all three dietary scores were significantly different across 6 Hispanic/Latino background groups (all P < 0.001), with highest (i.e., healthiest) in those of Mexican background and lowest in those of Puerto Rican background. Compared to non-mainland-US-born Hispanics/Latinos, mainland-US-born Hispanics/Latinos had significantly lower dietary scores (P < 0.001). Differences in dietary scores between mainland-US-born and non-mainland-US-born Hispanics/Latinos were majorly driven by differences in dietary intakes of healthy plant-based foods. After adjusting for multiple covariates, significantly lower risk ratios (95% CI) of CVD were observed for one standard deviation increment of the dietary scores, with 0.74 (0.60,0.91) for aMED, 0.80 (0.63,1.00) for HEI-2015, and 0.74 (0.60,0.93) for hPDI. Conclusions Although adherence to healthy eating patterns varies by Hispanic/Latino backgrounds and generations, greater adherence to these eating patterns is associated with lower risk of CVD across diverse US Hispanics/Latinos.

Metabolomic signatures of incident diabetes remain largely unclear for US Hispanics/Latinos, a group with high diabetes burden. We evaluated the associations of 624 known serum metabolites (measured by a global, untargeted approach) with incident diabetes in a subsample (n = 2010) of the Hispanic Community Health Study/Study of Latinos without diabetes and cardiovascular disease at baseline (2008-2011). On the basis of the significant metabolites associated with incident diabetes, metabolite modules were detected using topological network analysis and their associations with incident diabetes and longitudinal changes in cardiometabolic traits were further examined. There were 224 incident cases of diabetes after on average 6 years of follow-up. After adjustment for sociodemographic, behavioral and clinical sociodemographic and clinical diabetes risk factors, 134 metabolites were associated with incident diabetes (FDR-adjusted P<0.05). We identified 10 metabolite modules, including modules comprised of previously reported diabetes-related metabolites (e.g., sphingolipids, phospholipids, branched-chain and aromatic amino acids, and glycine) and two reflecting potentially novel metabolite groups (e.g., threonate, N-methylproline, oxalate, and tartarate in a plant-food metabolite module; and androstenediol sulfates in an androgenic-steroid metabolite module). The plant-food metabolite module and its components were associated with higher diet quality (especially higher intakes of healthy plant-based foods), lower risk of diabetes, and favorable longitudinal changes in HOMA-IR. The androgenic-steroid module and its component metabolites decreased with increasing age and were associated with higher risk of diabetes and greater increases in 2-h glucose over time. We replicated the associations of both modules with incident diabetes in a US cohort of non-Hispanic Blacks and Whites (n = 1754). Among US Hispanics/Latinos we identified metabolites across various biological pathways, including those reflecting androgenic steroids and plant-derived foods, associated with incident diabetes and changes in glycemic traits, highlighting the importance of hormones and dietary intake in the pathogenesis of diabetes.

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